In Situ Small Blood Vessel Electrical Response to Verapamil in Spontaneously Hypertensive Rats

  • W. J. Stekiel
  • M. J. Burke
  • S. J. Contney
  • J. H. Lombard
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 39)


Changes in vascular smooth muscle tone in hypertension — Development of essential hypertension in man and in the genetically altered spontaneously hypertensive rat (SHR) model of this disease is characterized hemodynamically by a transient elevation in cardiac output, a sustained elevation in total peripheral resistance (TPR) and a reduction in venous capacitance (1,2). The results of many investigations indicate that, in addition to pressure mediated structural adaptation on the arterial side of the circulation (3,4), an increased vascular smooth muscle (VSM) tone contributes significantly to the latter two hemodynamic changes. In the SHR model this increase in VSM tone includes an elevated sympathetic efferent input (5,6) which may be the result of an alteration in a central nervous sensing system (7). In addition, defects in the SHR VSM cell membrane mechanisms that regulate intracellular “activator calcium” (Cai) and therefore excitation-contraction coupling have been postulated to explain observed elevated sensitivity to external neurogenic and humoral influences in certain vessels (7,8,9,10). The defects in these membrane regulatory mechanisms and their temporal relation to the development and maintenance of the elevated VSM tone in SHR remain to be established, particularly in the small resistance and capacitance vessels. In addition to transmembrane ionic flux measurements (11,12), two other important parameters that can be used to assess changes in these membrane regulatory mechanisms are the VSM transmembrane potential (Em)(6,13,14) and the contractile force (7,8,9).


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Trippodo N, Frohlich E. Similarities of genetic (spontaneous) hypertension—man and rat. Circ. Res. (48): 309–319, 1981PubMedCrossRefGoogle Scholar
  2. 2.
    Smith TL, Hutchins, PM. Central hemodynamics in the developmental stage of spontaneous hypertension in the unanesthetized rat. Hypertension (1): 508–517, 1979.PubMedCrossRefGoogle Scholar
  3. 3.
    Folkow B, Hallbach M, Lundgren Y, Weiss L. Structurally based increase in flow resistance in spontaneously hypertensive rats. Acta Physiol. Scand. (79): 373–378, 1970.PubMedCrossRefGoogle Scholar
  4. 4.
    Folkow B. Cardiovascular structural adaptation; its role in the initiation and maintenance of primary hypertension. Clin. Sci. Mol. Med. (55): 3s–22s, 1978.Google Scholar
  5. 5.
    Yamori Y. Neurogenic mechanisms of spontaneous hypertension. In: Onesti G, Fernandes M, Kim K (Eds) Regulation of Blood Pressure by the CNS, Grune and Stratton, New York, 1976, pp. 65–76.Google Scholar
  6. 6.
    Harder DR, Contney SJ, Willems WJ, Stekiel WJ. Norepinephrine effect on in situ venous membrane potential in spontaneously hypertensive rats. Am. J. Physiol. (240) (Heart Circ. Physiol. 9): H837–H842, 1981.PubMedGoogle Scholar
  7. 7.
    Bohr D. What makes the pressure go up? A hypothesis. Hypertension (3) (Suppl): II160-II165, 1981Google Scholar
  8. 8.
    Webb RC, Bohr D. Recent advances in the pathogenesis of hypertension: Consideration of structural, functional, and metabolic vascular abnormalities resulting in elevated arterial resistance. Am. Heart J. (102): 251–264, 1981.PubMedCrossRefGoogle Scholar
  9. 9.
    Mulvany MJ. Do resistance vessel abnormalities contribute to the elevated blood pressure of spontaneously hypertensive rats? Bloodvessels (20): 1–22, 1983.Google Scholar
  10. 10.
    Toggart EJ(Jr), Zelis R. The role of calcium blockers in the treatment of other cardiovascular disorders. In: Flaim SF, Zelis R (eds) Calcium Blockers, Urban and Schwarzenberg, Baltimore-Munich, 1982, pp. 265–283.Google Scholar
  11. 11.
    Jones AW. Vascular smooth muscle alterations during hypertension. In: Bulbring E, Brading A, Jones A, Tomita T (eds) Smooth Muscle, Univ. of Texas Press, Austin, 1981, pp. 297–429.Google Scholar
  12. 12.
    Van Breemen C, Manzel A, Fahim M, Meisheri K. Selectivity of calcium antagonistic action in vascular smooth muscle. Am. J. Cardiol. (49): 507–510, 1982.PubMedCrossRefGoogle Scholar
  13. 13.
    Stekiel WJ, Contney SJ, Lombard JH, Willems WJ. Effect of adrenergic denervation on small mesenteric vessel membrane potential responses to noradrenaline in spontaneously hypertensive and Wistar-Kyoto rats. In: Rascher W, Clough D, Ganten D (eds) Hypertensive Mechanisms. The SHR as a Model to Study Human Hypertension, Schattauer, New York, 1982, pp. 252–255.Google Scholar
  14. 14.
    Hermsmeyer K, Trapani A, Abel PW. Membrane potential-dependent tension in vascular muscle. In: Vanhoutte PM, Leusen I (eds) Vasodilation, Raven Press, New York, 1981, pp. 273–284.Google Scholar
  15. 15.
    Nghiem C, Swamy VC, Triggle DJ. Inhibition by methoxyverapamil of the responses of smooth muscle from spontaneously hypertensive and normotensive rats. Blood Vessels (19): 177–185, 1982.PubMedGoogle Scholar
  16. 16.
    Stekiel WJ, Contney SJ, Lombard JH, Harder DR. Response of venous membrane potentials to calcium blockade in spontaneous hypertension. Hypertension 5 (Suppl I) 164–169, 1983.Google Scholar
  17. 17.
    Aprigliano O, Hermsmeyer K. In vitro denervation of the portal and caudal artery in the rat. J. Pharmacol. Exp. Ther. (198) 568–577, 1976.PubMedGoogle Scholar
  18. 18.
    Johansson B, Somlyo A. Electrophysiology and excitation- contraction coupling. In: Bohr DF, Somlyo AP, Sparks HV (eds) Handbook of Physiology, Sect. 2, Vol. I, Am. Physiol. Soc., Bethesda MD 1980, pp. 301–323.Google Scholar
  19. 19.
    Harder DR. Membrane electrical activation of arterial smooth muscle. In: Crass MF and Barnes CE (eds) Vascular Smooth Muscle: Metabolic, Ionic and Contractile Mechanisms, Academic Press, New York, 1982, pp. 71–97.CrossRefGoogle Scholar
  20. 20.
    Hermsmeyer K. Electrogenic ion pumps and other determinants of membrane potential in vascular muscle. Physiologist (25): 454–465, 1982.PubMedGoogle Scholar
  21. 21.
    Janis RA, Triggle DJ. New developments in Ca channel antagonists. J. Med. Chem. (26): 775–785, 1983.PubMedCrossRefGoogle Scholar
  22. 22.
    Loutzenhizer R, van Breemen C. Mechanisms of stimulated Ca2+ influx and consequences of influx inhibition. In: Merrill GF, Weiss HR (eds). Ca2+Entry Blockers, Adenosine and Neuro-humors, Urban and Schwarzenberg, Baltimore-Munich, 1983, pp. 73–89.Google Scholar
  23. 23.
    Flaim SF. Comparative pharmacology of calcium blockers based on studies of vascular smooth muscle. In: Flaim SF, Zelis R (eds) Calcium Blockers, Urban and Schwarzenberg, Baltimore- Munich, 1982, pp. 155–178.Google Scholar
  24. 24.
    Walsh JV, Singer JJ. Penetration-induced hyperpolarization as evidence for Ca2+ activation of K+ conductance in isolated smooth muscle cells. Am. J. Physiol. 239 (Cell Physiol(8)): C182–C189, 1980.PubMedGoogle Scholar
  25. 25.
    Meecn RW. Calcium-dependent potassium activation in nervous tissues. Ann. Rev. Biophys. Bioeng. (7): 1–18, 1978.CrossRefGoogle Scholar
  26. 26.
    Noon JP, Rice PJ, Baldessarini RJ. Calcium leakage as a cause of the high resting tension in vascular smooth muscle from the spontaneously hypertensive rat. Proc. Natl. Acad. Sci. USA (75): 605–607, 1975.Google Scholar
  27. 27.
    Kwan CY, Belbeck L, Daniel EE. Abnormal biochemistry of vascular smooth muscle plasma membrane as an important factor in the initiation and maintenance of hypertension in rat. Blood Vessels (16): 259–268, 1979.PubMedGoogle Scholar
  28. 28.
    Deonyck MA, Pernollet MG, Nunez AM, Meyer P. Calcium binding alterations in plasma membrane from various tissues of spontaneously hypertensive rats. Clin. Exp. Hypertens. (3): 797–801, 1981.CrossRefGoogle Scholar
  29. 29.
    Stanfield PR. Tetraethylammonium ions and the potassium permeability of excitable cells. Rev. Physiol. Biochem. Pharmacol. 97: 1–67, 1983.PubMedCrossRefGoogle Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1984

Authors and Affiliations

  • W. J. Stekiel
    • 1
  • M. J. Burke
    • 1
  • S. J. Contney
    • 1
  • J. H. Lombard
    • 1
  1. 1.Dept. of PhysiologyMedical College of WisconsinMilwaukeeUSA

Personalised recommendations