The Peripheral Circulation in Heart Failure

  • Alan T. Hirsch
  • Mark A. Creager


The development and progression of myocardial failure are heralded by the activation of circulating neurohormonal systems that modulate both vascular tone and renal retention of salt and water. In addition, the peripheral Circulation undergoes local changes in response to heart failure that are fundamental to the pathophysiology of this disease state. The fractional distribution of blood flow to the kidneys, limbs, and splanchnic beds decreases, whereas blood flow to the heart and brain is preserved.1,2 The diminished exercise capacity of limb muscles in patients with heart failure may be due, in part, to chronically diminished nutritive perfusion.3,4 Renal hypoperfusion and altered intrarenal hemodynamics may contribute to sodium and water retention.5,6 Previous chapters have focused on the mechanisms underlying systemic activation of the sympathetic nervous system, the renin-angiotensin system, as well as other circulatory neurohormones, such as arginine vasopressin and atrial natriuretic factor.


Heart Failure Congestive Heart Failure Atrial Natriuretic Peptide Atrial Natriuretic Factor Gestive Heart Failure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Leithe ME, Margorien RD, Hermiller JB, Unverferth DV, Leier CV. Relationship between central hemodynamics and regional blood flow in normal subjects and in patients with congestive heart failure. Circulation. 1984;69:57–64.PubMedGoogle Scholar
  2. 2.
    Zelis R, Flaim SF. Alterations in vasomotor tone in congestive heart failure. Prog Cardiovasc Dis. 1982;24:437–459.PubMedGoogle Scholar
  3. 3.
    Wiener DH, Maris J, Chance B, Wilson JR. Detection of skeletal muscle hypoperfusion during exercise using phosphorus-31 nuclear magnetic resonance spectroscopy. J Am Coll Cardiol. 1986;7:793–799.PubMedGoogle Scholar
  4. 4.
    Wilson JR, Wiener DH, Fink LI, Ferraro N. Vasodilatory behavior of skeletal muscle arterioles in patients with nonedematous chronic heart failure. Circulation. 1986;74:775–779.PubMedGoogle Scholar
  5. 5.
    Creager MA, Halperin AL, Bernard DB, et al. Acute regional circualtory and renal hemodynamic effects of converting-enzyme inhibition in patients with congestive heart failure. Circulation. 1981;64:483–489.PubMedGoogle Scholar
  6. 6.
    Cody RJ, Covit AB, Schaer GL, Laragh JH, Sealey JE, Feldschuh J. Sodium and water balance in chronic congestive heart failure. J Clin Invest. 1986;77:1441–1452.PubMedGoogle Scholar
  7. 7.
    Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288:373–376.PubMedGoogle Scholar
  8. 8.
    Ignarro LJ, Burns RE, Buga GM, Wood KS. Endothelium-derived relaxing factor from pulmonary artery and vein posesses pharmacologic and chemical properties identical to those of nitric oxide radical. Circ Res. 1987;61:866–879.PubMedGoogle Scholar
  9. 9.
    Palmer RMJ, Ferridge AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327:524–526.PubMedGoogle Scholar
  10. 10.
    Myers PR, Guerra R, Harrison DG. Release of NO and EDRF from cultured bovine aortic endothelial cells. Am J Physiol. 1989;256:H1030–H1037.PubMedGoogle Scholar
  11. 11.
    Ignarro LJ. Biological action and properties of endothelium-derived nitric oxide formed and released from artery and vein. Circ Res. 1989;65:1–21.PubMedGoogle Scholar
  12. 12.
    Cohen RA, Zitnay KM, Haudenschild CC, Cunningham LD. Loss of selective endothelial cell vasoactive functions in pig coronary arteries caused by hypercholesterolemia. Circ Res. 1988;63:903–910.PubMedGoogle Scholar
  13. 13.
    DeMey JG, Vanhoutte PM. Heterogeneous behavior of the canine arterial and venous wall: Importance of the endothelium. Circ Res. 1982;51:439–447.Google Scholar
  14. 14.
    Shimokawa H, Vanhoutte PM. Impaired endothelium-dependent relaxation to aggregating platelets and related vasoactive substances in porcine coronary arteries in hypercholesterolemia and atherosclerosis. Circ Res. 1989;64:900–914.PubMedGoogle Scholar
  15. 15.
    Rees DD, Palmer RMJ, Moncada S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci USA. 1989;86:3375–3378.PubMedGoogle Scholar
  16. 16.
    Vallance P, Collier J, Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet. 1989;2:997–1000.PubMedGoogle Scholar
  17. 17.
    Luscher TF, Vanhoutte PM. Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat. Hypertension. 1986;8:344–348.PubMedGoogle Scholar
  18. 18.
    Luscher TF, Vanhoutte PM, Raij L. Antihypertensive treatment normalizes decreased endothelium-dependent relaxations in rats with salt-induced hypertension. Hypertension. 1987;(suppl III):III193–III197.Google Scholar
  19. 19.
    Lockette W, Otsuka Y, Carretero OA. The loss of endothelium-dependent relaxation in hypertension. Hypertension. 1986;8:1161–1166.Google Scholar
  20. 20.
    Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE. Abnormal endothelim-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990;323:22–27.PubMedGoogle Scholar
  21. 21.
    Ontkean MT, Gay R, Greenberg B. Diminished endothelium-derived relaxing factor activity in an experimental model of chronic heart failure. Circ Res. 1991;69:1088–1096.PubMedGoogle Scholar
  22. 22.
    Kaiser L, Spickard RC, Olivier NB. Heart failure depresses endothelium-dependent responses in canine femoral artery. Am J Physiol. 1989;256:H962–H967.PubMedGoogle Scholar
  23. 23.
    Elsner D, Muntze A, Riegger AJR. The increase in total peripheral resistance by inhibition of EDRF-synthesis is attenuated in conscious dogs with heart failure.Circulation. 1990;III–591. Abstract.Google Scholar
  24. 24.
    Hildebrand FL Jr, Perrella MA, Burnett JD Jr. The role of endothelium-derived relaxing factor in experimental congestive heart failure. J Am Coll Cardiol. 1991; 17:281A. Abstract.Google Scholar
  25. 25.
    Main JS, Forster C, Armstrong PW. Inhibitory role of the coronary arterial endothelium to alpha-adrenergic stimulation in experimental heart failure. Circ Res. 1991;68:940–946.PubMedGoogle Scholar
  26. 26.
    Treasure CB, Vita JA, Cox DA, et al. Endothelium-dependent dilation of the coronary microvasculature is impaired in dilated cardiomyopathy. Circulation. 1990;81:772–779.PubMedGoogle Scholar
  27. 27.
    Kubo SH, Rector TS, Bank AJ, Williams RE, Heifetz SM. Endothelium-dependent vasodilation is attenuated in patients with heart failure. Circulation. 1991;84:1589–1596.PubMedGoogle Scholar
  28. 28.
    Kubo SH, Rector TS, Bank AJ, et al. Heart transplantation reverses abnormalities in endothelium dependent vasodilation of peripheral blood vessels in patients with heart failure. Circulation. 1991;84:II469.Google Scholar
  29. 29.
    Rubanyi GM. Cardiovascular Significance of Endothelium-derived Vasoactive Factors. Mount Kisco, NY: Futura Publishing, 1991.Google Scholar
  30. 30.
    Dzau VJ, Colucci WS, Hollenberg NK, Williams GH. Relation of the renin-angiotensin-aldosterone system to clinical state in congestive heart failure.Circulation. 1981;63:645–651.PubMedGoogle Scholar
  31. 31.
    Oliver JA, Sciacca R, Pinto J, Cannon PJ. Participation of the prostaglandins in the control of renal blood flow during acute reduction of cardiac output in the dog. J Clin Invest. 1981;67:229–237.PubMedGoogle Scholar
  32. 32.
    Friedman PL, Brown EJ Jr, Gunther S, et al. Coronary vasoconstrictor effect of indomethacin in patients with coronary artery disease. N Engl J Med. 1981;305:1171–1175.PubMedGoogle Scholar
  33. 33.
    Shebuski RJ, Aiken JW. Angiotensin II stimulation of renal prostaglandin synthesis elevated circulating prostacyclin in the dog. J Cardiovasc Pharmacol. 1980; 2:667–677.PubMedGoogle Scholar
  34. 34.
    Zusman RM, Keiser HR. Prostaglandin biosynthesis by rabbit renomedullary interstitial cells in culture: stimulation by angiotensin II, bradykinin and arginine vasopressin. J Clin Invest. 1977;60:215–223.PubMedGoogle Scholar
  35. 35.
    McGiff JC, Crawshaw K, Terragne NA, Malik KU, Lonigro AJ. Differential effect of noradrenaline and renal nerve stimulation on vascular resistance in the dog kidney and the release of a prostaglandin E-like substance. Clin Sci. 1972;42:223–233.PubMedGoogle Scholar
  36. 36.
    Dzau VJ, Packer M, Lilly LS, Swartz SL, Hollenberg NK, Williams GH. Prostaglandins in severe heart failure: Relation to renin-angiotensin system and hyponatremia. N Engl J Med. 1984;310:347–352.PubMedGoogle Scholar
  37. 37.
    Swartz SL, Williams GH. Angiotensin-Converting enzyme inhibition and prostaglandins. Am J Cardiol. 1982;49:1405–1409.PubMedGoogle Scholar
  38. 38.
    Moore TJ, Crantz FR, Hollenbert NK, et al. Contribution of prostaglandins to the antihypertensive action of Captopril in essential hypertension. Hypertension. 1981;3:168–173.PubMedGoogle Scholar
  39. 39.
    Dzau VJ, Creager MA. Prostaglandins in congestive heart failure. In: Robertson JIS, ed. The Renin-Angiotensin System. London: Gower Medical; 1986:912–918.Google Scholar
  40. 40.
    Lavin RI, Jaffe EA, Weksler BB, Tack-Goldman K. Nitroglycerin stimulates synthesis of prostacyclin by cultured human endothelial cells. J Clin Invest. 1981;67:762–769.Google Scholar
  41. 41.
    Morcillio E, Reid PR, Dubin N, Ghodgaonkar R, Pitt B. Myocardial prostaglandin E release by nitroglycerin and modification by indomethacin. Am J Cardiol. 1980;45:53–57.Google Scholar
  42. 42.
    Rubin IJ, Lazar JD. Influence of prostaglandin synthesis inhibitors on pulmonary vasodilatory effects of hydralazine in dogs with hypoxic pulmonary vasoconstriction. J Clin Invest. 1981;67:193–200.PubMedGoogle Scholar
  43. 43.
    Yanagisawa M, Kurihara S, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332:411–415.PubMedGoogle Scholar
  44. 44.
    Wu-Wong JR, Budzik GP, Devine EM, Opgenorth TJ. Characterization of endothelin converting enzyme in rat lung. Biochem Biophys Res Commun. 1990;171:1291–1296.PubMedGoogle Scholar
  45. 45.
    Yanagisawa M, Masaki T. Endothelin, a novel endothelium-derived peptide: pharmacological activities, regulation and possible roles in cardiovascular control. Biochem Pharm. 1989;38:1877–1883.PubMedGoogle Scholar
  46. 46.
    Resink TJ, Hahn AWA, Scott-Burden T, Powell J, Weber E, Buhler FR. Inducible endothelin mRNA expression and peptide secretion in cultured human vascular smooth muscle cells. Biochem Biophys Res Commun. 1990;168:1303–1310.PubMedGoogle Scholar
  47. 47.
    Brenner BM, Troy JL, Ballerinan BJ. Endothelium-dependent vascular responses: mediators and mechanisms. J Clin Invest. 1989;84:1373–1378.PubMedGoogle Scholar
  48. 48.
    Yoshizumi M, Kurihara H, Sugiyama T, et al. Hemodynamic shear stress stimulates endothelin production by cultured endothelial cells. Biochem Biophys Res Commun. 1989;161:859–864.PubMedGoogle Scholar
  49. 49.
    Masaki T, Kimura S, Yanagisawa M, Goto K. Molecular and cellular mechanism of endothelin regulation implications for vascular function. Circulation. 1991;84:1457–1468.PubMedGoogle Scholar
  50. 50.
    Marsden PA, Danthuluri NR, Brenner BM, Ballerman BM, Brock TA. Endothelin action on vascular smooth muscle involves inositol trisphosphate and calcium mobilization. Biochem Biophys Res Commun. 1989;158:86–93.PubMedGoogle Scholar
  51. 51.
    Resink TJ, Scott-Burden T, Buhler FR. Activation of phospholipase A2 by endothelin in cultured vascular smooth muscle cells. Biochem Biophys Res Commun. 1989;158:279–286.PubMedGoogle Scholar
  52. 52.
    Simonson MS, Wann S, Mene P, et al. Endothelin stimulates phospholipase C, Na+/H+ exchange, c-fos expression and mitogenesis in rat mesangial cells. J Clin Invest. 1989;83:708–712.PubMedGoogle Scholar
  53. 53.
    Ando K, Hirata YU, Shichiri M, Emori T, Marumo F. Presence of immunoreactive endothelin in human plasma. FEBS Lett. 1989;245:164–166.PubMedGoogle Scholar
  54. 54.
    Saito Y, Nakao K, Mukoyama M, Imura H. Increased plasma endothelin level in patients with essential hypertension. N Engl J Med. 1989;322:205.Google Scholar
  55. 55.
    Ogburn PL, Thompson RL, Lerman A, Burnett JC Jr. Endothelin elevation in normal preganancy and preeclampsia. Am J Obstet Gynecol. 1990;164:274.Google Scholar
  56. 56.
    Lerman A, Hallet JW, Heublein DM, Burnett JC Jr. A role for endothelin as a marker of diffuse atherosclerosis in the human. J Am Coll Cardiol. 1991;17:370A. Abstract.Google Scholar
  57. 57.
    King AJ, Pfeffer JM, Pfeffer MA, Brenner BM. Systemic hemodynamic effects of endothelin in rats. Am J Physiol. 1990;258:H787–H792.PubMedGoogle Scholar
  58. 58.
    Knuepfer MM, Han SP, Trapani AJ, Fok KF, Westfall TC. Regional hemodynamic and baroreflex effects of endothelin in rats. Am J Physiol. 1989;251 (Heart Circ Physiol 26):H918–H926.Google Scholar
  59. 59.
    Otsuka A, Mikami H, Katahira K, et al. Haemodynamic effect of endothelin, a novel potent vasconstrictor in dogs. Clin Exp Pharm Physiol. 1990;17:351–360.Google Scholar
  60. 60.
    Miller WI, Redfield MM, Burnett JC Jr. Integrated cardiac, renal, and endocrine actions of endothelin. J Clin Invest. 1989;83:317–320.PubMedGoogle Scholar
  61. 61.
    Goetz KL, Wang BC, Madwed JB, Zhu JL, Leadley RJ Jr. Cardiovascular, renal and endocrine responses to intravenous endothelin in conscious dogs. Am J Physiol. 1988;255(Heart Circ Physiol 24):R1064–R1068.PubMedGoogle Scholar
  62. 62.
    Vigne P, Laxdunski M, Freiin C. The inotropic effect of endothelin-1 on rat atria involves hydrolysis of phosphatidylinositol. FEBS Lett. 1989;249:143–146.PubMedGoogle Scholar
  63. 63.
    Concas V, Laurent S, Brisac AM, Perret C, Safar M. Endothelin has potent direct inotropic and chronotropic effects in cultured heart cells. J Hypertens. 1989;7:S96–S97.Google Scholar
  64. 64.
    Hu JR, Hardorf RV, Lang RE. Endothelin has potent inotropic effects in rat atria. Eur J Pharmacol. 1988;158:275–278.PubMedGoogle Scholar
  65. 65.
    Lembeck F, Decrinis M, Pertl C, Amann R, Donner J. Effects of endothelin on the cardiovascular system and on smooth muscle preparations in different species. Naunyn-Scmiedeberg’s Arch Pharmacol. 1989;340:744–751.Google Scholar
  66. 66.
    Ishikawa T, Yanagisawa M, Kimura S, Goto K, Masaki T. Positive chronotropic effects of endothelin, a novel endothelium-derived vasconstrictor peptide. Pfluger Arch. 1988;413:108–110.Google Scholar
  67. 67.
    Kramer BK, Nishida M, Kelly RA, Smith TW. Endothelins: myocardial actions of a new class of cytokines. Circulation. 1992;85:350–356.PubMedGoogle Scholar
  68. 68.
    Stasch JP, Hirth-Kietrick C, Kazda S, Neuser D. Endothelin stimulates release of atrial natriuretic peptides in vitro and in vivo. Life Sci.. 1989;45:869–875.PubMedGoogle Scholar
  69. 69.
    Schiebinger RJ, Gomez-Sanchez CE. Endothelin: a potent stimulus of atrial natriuretic peptide secretion by superfused rat atria and its dependency on calcium. Endocrinology. 1990;127:119–125.PubMedGoogle Scholar
  70. 70.
    Cavero PG, Miller WL, Heublein DM, Margulies KB, Burnett JC. Endothelin in experimental congestive heart failure in the anesthetized dog. Am J Physiol. 1990;259:F312–F317.PubMedGoogle Scholar
  71. 71.
    Margulies KB, Hildebrand FL Jr, Lerman A, Perrella MA, Burnett JC Jr. Increased endothelin in experimental heart failure. Circulation. 1990;82:2226–2230.PubMedGoogle Scholar
  72. 72.
    Robertston R, Susawa T, Sugiura M, et al. Circulating endothelin levels: modulation by heart failure in man. Clin Res. 1990;38:414A. Abstract.Google Scholar
  73. 73.
    Stewart DJ, Cernacek P, Costello KB, Rouleau JL. Elevated endothelin-1 in heart failure and loss of normal response to postural change. Circulation. 1992;85: 510–517.PubMedGoogle Scholar
  74. 74.
    Cody RJ, Haas GJ, Binkley PF, Capers Q, Kelley R. Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic congestive heart failure.Circulation. 1992;85:504–509.PubMedGoogle Scholar
  75. 75.
    Ray SG, McMurray J, Morton JJ. Endothelin and atrial natriuretic factor in acute myocardial infarction. Circulation. 1990;82(suppl III):III–279. Abstract.Google Scholar
  76. 76.
    Cernacek P, Stewart D. Immunoreactive endothelin in human plasma: marked elevations in patients in cardiogenic shock. Biochem Biophys Res Commun. 1989;161:562–567.PubMedGoogle Scholar
  77. 77.
    Emori T, Hirata Y, Ohta K, Shichiri M, Marumo F. Secretory mechanism of immunoreactive endothelin in cultured bovine endothelial cells. Biochem Biophys Res Commun. 1989;160:93–100.PubMedGoogle Scholar
  78. 78.
    Wakenlin GE. Antibodies to renin as proof of the pathogenesis of sustained renal hypetension. Circulation. 1958;17:653–657.Google Scholar
  79. 79.
    Dzau VJ, Copelman RI, Barger AC, Haber E. Reninspecific antibody for study of cardiovascular homeostasis. Science. 1980;207:1091–1093.PubMedGoogle Scholar
  80. 80.
    Pals DT, Masucci FD, Sipos F, Denning GS. A specific competitive antagonist of the vascular action of angiotensin II. Circ Res. 1971;29:664–647.PubMedGoogle Scholar
  81. 81.
    Ondetti MA, Rubin B, Cushman DW. Design of specific inhibitors of angiotensin converting enzyme: new class of orally active antihypertensive agents. Science. 1977; 196:441–444.PubMedGoogle Scholar
  82. 82.
    Brunner HR, Gavras H, Waeber B, et al. Oral angiotensin-converting enzyme inhibitor in long-term treatment of hypertensive patients. Ann Intern Med. 1979;90:19–23.PubMedGoogle Scholar
  83. 83.
    Wenting GJ, Blankestijn PJ, Pldermans D, et al. Blood pressure response of nephrectomized subjects and patients with essential hypertension to ramipril: indirect evidence that inhibition of tissue angiotensin converting enzyme is important. Am J Cardiol. 1987;59:92D–97D.PubMedGoogle Scholar
  84. 84.
    Kubo SH, Clark M, Laragh JH, Borer JS, Cody RJ. Identification of normal neurohormonal activity in mild congestive heart failure and stimulating effect of upright posture and diuretics. Am J Cardiol. 1987:60:1322–1328.PubMedGoogle Scholar
  85. 85.
    Creager MA, Faxon DP, Halperin SL, et al. Determinants of clinical response and survival in patients with congestive heart failure treated with Captopril. Am Heart J. 1982;104:1147–1153.PubMedGoogle Scholar
  86. 86.
    Dzau VJ, Re RN. Evidence for the existence of renin in the heart. Circulation. 1987;73(suppl I):I134–I136.Google Scholar
  87. 87.
    Philips MI, Stenstrom B. Angiotensin II in rat brain comigrates with authentic angiotensin II in high pressure liquid chromatography. Circ Res. 1985;56:212–219.Google Scholar
  88. 88.
    Deboben A, Inagami T, Ganten G. Tissue renin. In: Genest J, Kuchel O, Hamet P, eds. Hypertension. 2nd ed. New York: McGraw-Hill; 1983:194–209.Google Scholar
  89. 89.
    Field LS, McGowen RA, Dickensen DP, Gross KW. Tissue and gene specificity of mouse renin expression. Hypertension. 1984;6:597–603.PubMedGoogle Scholar
  90. 90.
    Lynch KR, Simnad VT, Ben-Ari ET, Maniatis T, Zinn K, Garrison JC. Localization of preangiotensinogen messenger RNA sequences in the rat brain. Hypertension. 1986;8:540–543.PubMedGoogle Scholar
  91. 91.
    Loudon M, Bing RF, Thurston H, Swales JD. Arterial wall uptake of renal renin and blood pressure control. Hypertension. 1983;5:629–634.PubMedGoogle Scholar
  92. 92.
    Oliver JA, Sciacca RR. Local generation of angiotensin II as a mechanism of regulation of peripheral vascular tone in the rat. J Clin Invest. 1984;4:1247–1251.Google Scholar
  93. 93.
    Dzau VJ, Gibbons GH. Autocrine-paracrine mechanisms of vascular myocytes in hypertension. Am J Cardiol. 1987;60:991–1031.Google Scholar
  94. 94.
    Rosenthal JH, Pfeiffer B, Mecheilor ML, Pschort J, Jacob ICM, Dahlheim H. Investigations of components of the renin-angiotensin system in rat vascular tissue. Hypertension. 1984;6:383–390.PubMedGoogle Scholar
  95. 95.
    Molteni A, Dzau VJ, Fallon JT, Haber E. Monoclonal antibodies as probes of renin gene expression.Circulation. 1984;70(suppl II):II–196. Abstract.Google Scholar
  96. 96.
    Mizuno K, Nakamaru M, Higashimori K, Inagami T. Local generation and release of angiotensin II in peripheral vascular tissue. Hypertension. 1988;11:223–229.PubMedGoogle Scholar
  97. 97.
    Aguirela G, Schirar A, Baukai A, Gatt KJ. Circulating angiotensin II and adrenal receptors after nephrectomy. Nature. 1981;289:507–509.PubMedGoogle Scholar
  98. 98.
    Campbell DJ. The site of angiotensin production. J Hypertens. 1985;3:730–737.Google Scholar
  99. 99.
    Admiraal PJJ, Darkx FHM, Jan Danser AH, Pierman H, Schalenkamp MADH. Metabolism and production of angiotensin II in different vascular beds in subjects with hypertension. Hypertension. 1990;15:44–55.PubMedGoogle Scholar
  100. 100.
    Shepherd JT, Vanhoutte PM, George E. Brown memorial lecture: local modulation of adrenergic neurotransmission. Circulation. 1981;64:655–666.PubMedGoogle Scholar
  101. 101.
    Longnecker DJ, Durcus MI, Donovan KR, Miller ED, Peach MJ. Saralasin dilates arterioles in SHR but not WKYrats. Hypertension. 1984;l(suppl I):106–110.Google Scholar
  102. 102.
    Riegger AJG, Lever AF, Miller JA, Morton JJ, Slack B. Correction of renal hypertension in the rat by prolonged infusion of saralasin. Lancet. 1977;2:1317–1319.PubMedGoogle Scholar
  103. 103.
    Okamura T, Miyazcki M, Inagemi T, Toda N. Vascular renin-angiotensin system in two-kidney, one clip hypertensive rats. Hypertension. 1986;8:560–565.PubMedGoogle Scholar
  104. 104.
    Unger T, Ganten D, Lang RE, Scholkens VA. Is tissue converting inhibition a determinant of the antihypertensive efficacy of converting enzyme inhibitors? Studies with two different compounds Hoe 398 and MD 421 in spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1985;7:36–41.PubMedGoogle Scholar
  105. 105.
    Kaplan HR, Taylor DG, Olson SC, Andrews LK. Quinapril—a preclinical review of the pharmacology, pharmacokinetics, and toxicology. Angiology. 1989; 40:335–350.PubMedGoogle Scholar
  106. 106.
    Simon ACH, Levenson JA, Bouther JI, Safar ME. Comparison of oral MK 421 and propranolol in mild to moderate hypertension and their effects on arterial and venous vessels of the forearm. Am J Cardiol. 1984;53:781–783.PubMedGoogle Scholar
  107. 107.
    Dzau VJ, Safar MI. Large conduit arteries in hypertension: role of the vascular renin angiotensin system. Circulation. 1988;77:947–954.PubMedGoogle Scholar
  108. 108.
    Taugner R, Hackenthal E, Helmchen U, et al. The intrarenal renin-angiotensin system. An immunocyto-chemical study on the localization of renin, angiotensinogen, converting enzyme, and the angiotensins in the kidney of mouse and rat. Klin Wochenschr. 1982;60:1218–1222.PubMedGoogle Scholar
  109. 109.
    Taugner R, Hackenthal E, Rix E, Nibiling R, Poulsen K. Immunocytochemistry of the renin-angiotensin system: renin, angiotensinogen, angiotensin I, angiotensin II, and converting enzyme in the kidneys of mice, rats, and tree shrews.Kidney Int. 1982;22:S33–S43.Google Scholar
  110. 110.
    Dzau VJ, Kreisbert JI. Cultured glomerular mesangial cells contain renin: influence of calcium and isoproterenol. J Cardiol Pharmacol. 1986;8(suppl 10):S6-S10.Google Scholar
  111. 111.
    Dzau VJ, Ellison KE, Brody T, Ingelfinger J, Pratt RE. A comparative study of the distributions of renin and angiotensinogen messenger ribonucleic acids in rat and mouse tissues. Endocrinology. 1987;120:2334–2338.PubMedGoogle Scholar
  112. 112.
    Ingelfinger JR, Pratt RE, Ellison K, Dzau VJ. Sodium regulation of angiotensinogen mRNA expression in rat kidney cortex and medulla. J Clin Invest. 1986;78:1311–1315.PubMedGoogle Scholar
  113. 113.
    Ingelfinger JR, Fon EA, Ellison KE, Dzau VJ. Localization of the intratenal renin angiotensin system (RAS) by in situ hybridization of renin and angiotensinogen (Ang-n) mRNAs. Kidney Int. 1988;33:269. Abstract.Google Scholar
  114. 114.
    Ingelfinger JR, Zuo WM, Fon EA, Ellison KE, Dzau VJ. In situ hybridization evidence for angiotensinogen messenger RNA in the rat proximal tubule. J Clin Invest. 1990;85:417–423.PubMedGoogle Scholar
  115. 115.
    Soubrier F, Alhene-Gelas F, Hubert C, et al. Two putative active centers in human angiotensin I converting enzyme revealed by molecular cloning. Proc Natl Acad Sci USA. 1988;85:9386–9390.PubMedGoogle Scholar
  116. 116.
    Sakaguchi K, Chai SY, Jackson B, Johnston CI, Mendelsohn FAO. Inhibition of tissue angiotensin converting enzyme. Quantitation by autoradiography. Hypertension. 1988;11:230–238.PubMedGoogle Scholar
  117. 117.
    Ingelfinger JR, Anderson S, Hirsch AT, Dzau VJ, Brenner BM. Elevation of renal angiotensin converting enzyme (ACE) activity in nephrotic rats. American Society of Nephrology, Proceedings of 22nd Annual Meeting, Washington, DC, 1989;168A. Abstract.Google Scholar
  118. 118.
    Seikaly MG, Arant BS Jr, Seney FD Jr. Measurement of endogenous angiotensin levels in glomerular filtrate and proximal tubule fluid. American Society of Nephrology, Proceedings of 22nd Annual Meeting, Washington, DC, 1989;171A. Abstract.Google Scholar
  119. 119.
    Campbell DJ, Habener JF. Angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat. J Clin Invest. 1986;78:31–39.PubMedGoogle Scholar
  120. 120.
    Ellison KE, Ingelfinger JR, Pivor M, Dzau VJ. Androgen regulation of rat renal angiotensinogen messenger RNA expression. J Clin Invest. 1989;83:1941–1945.PubMedGoogle Scholar
  121. 121.
    Schunkert H, Ingelfinger JR, Hirsch AT, et al. Evidence for tissue-specific activation of renal angiotensionogen mRNA expression in chronic stable experimental heart failure. J Clin Invest. 1992;90:1523–1529.PubMedGoogle Scholar
  122. 122.
    Creager MA, Halperin JL, Bernard DB, et al. Acute regional circulatory and renal hemodynamic effects of converting-enzyme inhibition in patients with congestive heart failure. Circulation. 1981;64:483–489.PubMedGoogle Scholar
  123. 123.
    Bank AJ, Kubo SH, Rector TS, Heifetz SM, Williams RE. Local forearm vasodilation with intra-arterial administration of enalaprilat in humans. Clin Pharmacol Ther. 1991;50:314–321.PubMedGoogle Scholar
  124. 124.
    Foult JM, Tavolaro O, Antony I, Nitenberg A. Direct myocardial and coronary effects of enalaprilat in patients with dilated cardiomyopathy: assessment by a bilateral intracoronary infusion technique. Circulation. 1988; 77:337–344.PubMedGoogle Scholar
  125. 125.
    Faxon DP, Halperin JL, Creager MA, Gavras H, Schick EC, Ryan TJ. Angiotensin inhibition in severe heart failure: acute central and limb hemodynamic effects of Captopril with observations on sustained oral therapy. Am Heart J. 1981;191:548–556.Google Scholar
  126. 126.
    Hoffman BB, Lefkowitz RJ. Alpha-adrenergic receptor subtypes. N Engl J Med. 1980;302:1390–1396.PubMedGoogle Scholar
  127. 127.
    Cotecchia S, Schwinn DA, Randall RR, Lefkowitz RJ, Caron MG, Kobilka BK. Molecular cloning and expression of the cDNA for the hamster alphal- adrenergic receptor. Proc Natl Acad Sci USA. 1988;85:7159–7163.PubMedGoogle Scholar
  128. 128.
    Schwinn DA, Lomasney JW, et al. Molecular cloning and expression of the cDNA for a novel alphar adrenergic receptor subtype. J Biol Chem. 1990; 265:8183–8189.PubMedGoogle Scholar
  129. 129.
    Han C, Abel PW, Minneman KP. Alpharadrenoceptor subtypes linked to different mechanisms for increasing intracellular Ca2+ in smooth muscle. Nature. 1987; 329:333–335.PubMedGoogle Scholar
  130. 130.
    Suzuki E, Tsujimoto G, Tamura K, Hashimoto K. Two pharmacologically distinct alphal-adrenoceptor subtypes in the contraction of rabbit aorta: each subtype couples with a different Ca2+ signalling mechanism and plays a different physiological role. Mol Pharmacol. 1990; 38:725–736.PubMedGoogle Scholar
  131. 131.
    Colucci WS, Gimbrone MA Jr, Alexander RW. Regulation of the postsynaptic alpha-adrenergic receptor in rat mesenteric artery. Effects of chemical sympathectomy and epinephrine treatment. Circ Res. 1981;48:104–111.PubMedGoogle Scholar
  132. 132.
    Tsujimoto G, Honda K, Hoffman BB, Hashimoto K. Desensitization of postjunctional alpha 1- and alpha 2-adrenergic receptor-mediated vasopressor response in rat harboring pheochromocytoma. Circ Res. 1987;61:86–98.PubMedGoogle Scholar
  133. 133.
    Colucci WS, Alexander RW. Norepinephrine-induced alteration in the coupling of alpharadrenergic receptor occupancy to calcium efflux in rabbit aortic smooth muscle cells. Proc Natl Acad Sci USA. 1986;83:1743–1746.PubMedGoogle Scholar
  134. 134.
    Izzo NJ Jr, Seidman CE, Collins S, Colucci WS. Alphar adrenergic receptor mRNA level is regulated by norepinephrine in rabbit aortic smooth muscle cells. Proc Natl Acad Sci USA. 1990;87:6268–6271.PubMedGoogle Scholar
  135. 135.
    Lurie KG, Tsujimoto G, Hoffman BB. Desensitization of alpha-1 adrenergic receptor-mediated vascular smooth muscle contraction. J Pharmacol Exp Ther. 1985; 234:147–152.PubMedGoogle Scholar
  136. 136.
    Goldberg MR, Robertson D. Evidence for the existence of vascular alpha2-adrenergic receptors in humans. Hypertension. 1984;6:551–556.PubMedGoogle Scholar
  137. 137.
    Lorenz W, Lomasney JW, Collins S, Regan JW, Caron MG, Lefkowitz RJ. Expression of three alpha2-adrenergic receptor subtypes in rat tissues: Implications for alpha2-receptor classification. Mol Pharmacol. 1990; 38:599–603.PubMedGoogle Scholar
  138. 138.
    Cotecchia S, Koblika BK, Daniel KW, et al. Multiple second messenger pathways of alpha-adrenergic receptor subtypes expressed in eukaryotic cells. J Biol Chem. 1990;265:63–69.PubMedGoogle Scholar
  139. 139.
    Ahlquist RP. A study of the adrenotropic receptors. Am J Physiol. 1948;153:586–600.PubMedGoogle Scholar
  140. 140.
    Emorine LJ, Marullo S, Briend-Sutrean M-M, et al. Molecular characterization of the human β 3-adrenergic receptor. Science. 1989;245:1118–1121.PubMedGoogle Scholar
  141. 141.
    Lefkowitz RJ, Stadel JM, Caron MG. Adenylate cyclase-coupled β-adrenergic receptors.Annu Rev Biochem. 1983;52:159–186.PubMedGoogle Scholar
  142. 142.
    Bulbring E, Tomita T. Catecholamine action on smooth muscle. Pharmacol Rev. 1987;39:49–96.PubMedGoogle Scholar
  143. 143.
    Hertel C, Perkins JP. Receptor-specific mechanisms of desensitization of β-adrenergic receptor function. Mol Cell Endocrinol. 1984;37:245.PubMedGoogle Scholar
  144. 144.
    Kassis S, Fishman PH. Different mechanisms of desensitization of adenylate cyclase by isoproterenol and prostaglandin E1 in human fibroblasts. J Biol Chem. 1982;257:5312–5318.PubMedGoogle Scholar
  145. 145.
    Strasser RH, Lefkowitz RJ. Homologous desensitization of β-adrenergic receptor coupled adenylate cyclase. J Biol Chem. 1985;260:4561–4564.PubMedGoogle Scholar
  146. 146.
    Vatner DE, Vatner SF, Nejima J, et al. Chronic norepinephrine elicits desensitization by uncoupling the β-receptor. J Clin Invest. 1989;84:1741–1748.PubMedGoogle Scholar
  147. 147.
    Vatner DE, Vatner SF, Fujii AM, Homcy CJ. Loss of high affinity cardiac β-adrenergic receptors in dogs with heart failure. J Clin Invest. 1985;76:2259–2264.PubMedGoogle Scholar
  148. 148.
    Brodde O-E, Daul A, Michel-Reher M, et al. Agonistinduced desensitization of α-adrenoceptor function in humans.Circulation. 1990;81:914–921.PubMedGoogle Scholar
  149. 149.
    Rothwell NJ, Stock MJ, Sudera DK. Changes in tissue blood flow and β-receptor density of skeletal muscle in rats treated with the β 2-adrenoreceptor agonist clenbuterol. Br J Pharmacol. 1987;90:601–607.PubMedGoogle Scholar
  150. 150.
    Colucci WS, Alexander RW, Williams GH, et al. Decreased lymphocyte a-adrenergic agonist pirbuterol. N Engl J Med. 1981;305:185–190.PubMedGoogle Scholar
  151. 151.
    Wilson JR, Lanoce V, Frey MJ, Ferraro N. Arterial baroreceptor control of peripheral vascular resistance in experimental heart failure. Am Heart J. 1990;119:1122–1130.PubMedGoogle Scholar
  152. 152.
    Forster C, Carter SL, Armstrong PW. Alpha1 adrenoceptor activity in arterial smooth muscle following congestive heart failure. Can J Physiol Pharmacol. 1989;67:110–115.PubMedGoogle Scholar
  153. 153.
    Creager MA, Hirsch AT, Dzau VJ, Nabel EG, Cutler SS, Colucci WS. Baroreflex regulation of regional blood flow in congestive heart failure. Am J Physiol. 1990; 258:H1409–H1414.PubMedGoogle Scholar
  154. 154.
    Kubo SH, Rector TS, Heifetz SM, Cohn JN. Alpha2-receptor mediated vasoconstriction in patients with congestive heart failure. Circulation. 1989;80:1660–1667.PubMedGoogle Scholar
  155. 155.
    Gilson N, el Houda Bouanani N, Corsin A, Crozatier B. Left ventricular function and β-adrenoceptors in rabbit failing heart. Am J Physiol. 1990;258:H634–H641.PubMedGoogle Scholar
  156. 156.
    Fan T-H, Liang C-S, Kawashima S, Banerjee SP. Alterations in cardiac β-adrenoceptor responsiveness and adenylate cyclase system by congestive heart failure in dogs. Eur J Pharmacol. 1987;140:123–132.PubMedGoogle Scholar
  157. 157.
    Bristow MR, Hershberger RE, Port JD. β-adrenergic pathways in nonfailing and failing human ventricular myocardium. Circulation. 1990;82:1–12.Google Scholar
  158. 158.
    Creager MA, Quigg RJ, Ren CJ, Roddy MA, Colucci WS. Limb vascular responsiveness to β-adrenergic receptor stimulation in patients with congestive heart failure. Circulation. 1991;83:1873–1879.PubMedGoogle Scholar
  159. 159.
    Walker BR. Evidence for a vasodilatory effect of vasopressin in the conscious rat. Am J Physiol. 1986;251: H34–H39.PubMedGoogle Scholar
  160. 160.
    Liard J-F. Cardiovascular effects associated with antidiuretic activity of vasopressin after blockade of its vasoconstrictor action in dehydrated dogs. Circ Res. 1986;58:631–640.PubMedGoogle Scholar
  161. 161.
    Hirsch AT, Dzau VJ, Majzoub JA, Creager MA. Vasopressin-mediated forearm vasodilation in normal humans; evidence for a vascular vasopressin V2 receptor. J Clin Invest. 1989;84:418–426.PubMedGoogle Scholar
  162. 162.
    Zusman RM, Keiser HR. Prostaglandin biosynthesis by rabbit renomedullary interstitial cells in tissue culture. Stimulation by angiotensin II, bradykinin, and arginine vasopressin. J Clin Invest. 1977;60:215–233.PubMedGoogle Scholar
  163. 163.
    Katusic ZS, Shepherd JT, Vanhoutte PM. Vasopressin causes endothelium-dependent relaxations of the canine basilar artery. Circ Res. 1984;55:575–579.PubMedGoogle Scholar
  164. 164.
    Yamane Y. Plasma ADH level in patients with chronic congestive heart failure. Jpn Circ J. 1968;32:745–759.PubMedGoogle Scholar
  165. 165.
    Szatalowicz VL, Arnold PE, Chaimovitz C, Bichet D, Berl T, Schrier RW. Radioimmunoassay of plasma arginine vasopressin in hyponatremic patients with congestive heart failure. N Engl J Med. 1981;305:263–266.PubMedGoogle Scholar
  166. 166.
    Riegger GAJ, Liebau G, Koehsiek K. Antidiuretic hormone in congestive heart failure. Am J Med. 1982;72:49–52.PubMedGoogle Scholar
  167. 167.
    Goldsmith SR, Francis GS, Cowley AW Jr, Levine TB, Cohn JN. Increased plasma arginine vasopressin levels in patients with congestive heart failure. J Am Coll Cardiol. 1983;1:1385–1390.PubMedGoogle Scholar
  168. 168.
    Creager MA, Faxon DP, Cutler SS, Kohlmann O, Ryan TJ, Gavras H. The contribution of vasopressin to vasoconstriction in patients with congestive heart failure: comparison to the renin-angiotensin system and the sympathetic nervous system. J Am Coll Cardiol. 1986;7:756–765.Google Scholar
  169. 169.
    Mulinari RA, Gavra I, Wang YX, Franco R, Gavras H. Effects of a vasopressin antagonist with combined antipressor and antidiuretic properties in rats with left ventricular dysfunction. Circulation. 1990;81:308–311.PubMedGoogle Scholar
  170. 170.
    Stone CK, Liang C, Imai N, Sakamoto S, Sladek CD, Hood WB. Short-term hemodynamic effects of vasopressin V1-receptor inhibition in chronic right-sided congestive heart failure. Circulation. 1988;78:1251–1259.PubMedGoogle Scholar
  171. 171.
    Nicod P, Waeber B, Bussein J-P, et al. Acute hemodynamic effect of a vascular antagonist of vasopressin in patients with congestive heart failure. Am J Cardiol. 1985;55:1043–1047.PubMedGoogle Scholar
  172. 172.
    Waldman SA, Rapoport RM, Murad F. Atrial natriuretic factor selectively activates particulate guanylate cyclase and elevates cyclic GMP in rat tissues. J Biol Chem. 1984;259:14332–14334.PubMedGoogle Scholar
  173. 173.
    Winquist RJ, Faison SA, Waldman SA, Schwartz K, Murad F, Rapoport RM. Atrial natriuretic factor elicits an endothelium-independent relaxation and activates particulate guanylate cyclase in vascular smooth muscle. Proc Natl Acad Sci USA. 1984;81:7661–7664.PubMedGoogle Scholar
  174. 174.
    Garcia R, Thibault G, Gutkowska J, Cantin M, Genest J. Changes of regional blood flow induced by atrial natriuretic factor (ANF) in conscious rats. Life Sci. 1985;36:1687–1692.PubMedGoogle Scholar
  175. 175.
    Ishihara T, Aisaka K, et al. Vasodilatory and diuretic actions of alpha-human atrial natriuretic polypeptide (alpha hANP). Life Sci. 1985;36:1205–1215.PubMedGoogle Scholar
  176. 176.
    Burnett JC Jr, Kao PC, Hu DC, et al. Atrial natriuretic peptide elevation in congestive heart failure in the human. Science. 1986;231:1145–1147.PubMedGoogle Scholar
  177. 177.
    Raine AEG, Erne P, Burgisser F, et al. Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure. N Engl J Med. 1986;31:533–537.Google Scholar
  178. 178.
    Cody RJ, Atlas SA, Laragh JH, et al. Atrial natriuretic factor in normal subjects and heart failure patients. J Clin Invest. 1986;78:1362–1374.PubMedGoogle Scholar
  179. 179.
    Creager MA, Hirsch AT, Nabel EG, Cutler SS, Colucci WS, Dzau VJ. Responsiveness of atrial natriuretic factor to reduction in right atrial pressure in patients with chronic congestive heart failure. J Am Coll Cardiol. 1988;11:1191–1198.PubMedGoogle Scholar
  180. 180.
    Kohzuki M, Hodsman GP, Johnston CI. Attenuated response to atrial natriuretic peptide in rats with myocardial infarction. Am J Physiol. 1989;256:H533–H538.PubMedGoogle Scholar
  181. 181.
    Hirooka Y, Takeshita A, Imaizumi T, et al. Attenuated forearm vasodilatative response to intra-arterial atrial natriuretic peptide in patient with heart failure. Circulation. 1990;82: 147–153.PubMedGoogle Scholar
  182. 182.
    Zelis R, Mason DT, Braunwald E. A comparison of peripheral resistance vessels in normal subjects and in patients with congestive heart failure. J Clin Invest. 1968;47:960–970.PubMedGoogle Scholar
  183. 183.
    Creager MA, Quigg RJ, Ren CJ, Roddy M, Colucci WS. Limb vascular responsiveness to β-adrenergic receptor stimulation in patients with congestive heart failure. Circulation. 1991;83:1873–1879.PubMedGoogle Scholar
  184. 184.
    Longhurst J, Gifford W, Zelis R. Impaired forearm oxygen consumption during statis exercise in patients with congestive heart failure. Circulation. 1976;54:447–480.Google Scholar
  185. 185.
    Zelis R, Mason DT. Diminished forearm arteriolar dilator capacity produced by mineralocorticoid-induced salt retention in man.Circulation. 1970;41:589–592.PubMedGoogle Scholar
  186. 186.
    Zelis R, Delea CS, Coleman HN, Mason DT. Arterial sodium content in experimental congestive heart failure. Circulation. 1970;61:213–216.Google Scholar
  187. 187.
    Zelis R, Lee G, Mason DT. Influence of experimental edema on metabolically determined blood flow. Circ Res. 1974;34:482–490.PubMedGoogle Scholar
  188. 188.
    Sinoway L, Minotti J, Musch T, et al. Enhanced metabolic vasodilation secondary to diuretic therapy in decompensated congestive heart failure secondary to coronary artery disease. Am J Cardiol. 1987;60:107–111.PubMedGoogle Scholar
  189. 189.
    Sinoway LI, Musch TI, Minotti JR, Zelis R. Enhanced maximal metabolic vasodilation in the dominant forearms of tennis players. J Appl Physiol. 1986;61:1076–1079.Google Scholar
  190. 190.
    Sinoway LI, Shenberger J, Wilson J, McLaughlin D, Musch T, Zelis R. A 30-day forearm work protocol increases maximal forearm blood flow. J Appl Physiol. 1987;62:1063–1067.PubMedGoogle Scholar
  191. 191.
    Sinoway LI, Minotti JR, Davis D, et al. Delayed reversal of impaired vasodilation in congestive heart failure after heart transplantation. Am J Cardiol. 1988;61:1076–1079.PubMedGoogle Scholar
  192. 192.
    Arnold JMO, Marchiori GE, Imrie JR, Bunton GL, Pflugfelden PW, Kostuk WJ. Large artery function in patients with chronic heart failure. Circulation. 1991;84:2418–2425.PubMedGoogle Scholar
  193. 193.
    Finkelstein SM, Cohn JN, Collins VR, Carlyle PF, Shelly WJ. Vascular hemodynamic impedance in congestive heart failure. Am J Cardiol. 1985;55:423–427.PubMedGoogle Scholar
  194. 194.
    Repine CJ, Nichols WW, Conti CR. Aortic input impedance in heart failure. Circulation. 1978;58:460–469.Google Scholar
  195. 195.
    Lage S, Kopel L, Monachini M, Coleman S, Polak J, Creager MA. Compliant properties of the carotid artery in congestive heart failure. Circulation. 1991;84:II–56.Google Scholar

Copyright information

© Springer-Verlag New York, Inc. 1994

Authors and Affiliations

  • Alan T. Hirsch
  • Mark A. Creager

There are no affiliations available

Personalised recommendations