Advertisement

Functional Modifications in Blood Vessels of Hypertensive Rats

  • Théophile Godfraind
  • Nicole Morel
Conference paper

Abstract

It has been reported that vascular smooth muscle from hypertensive animals shows hypersensitivity for vasoconstrictors (Holloway and Bohr 1973; Thompson et al. 1987; Boonen and De Mey 1990; Bodin et al. 1993). This hyperre-activity has been suggested to arise either from a change in receptor affinity (Nyborg and Bevan 1988), in receptor number, or in the transduction mechanisms of the receptor (Asano et al. 1988; Johnson et al. 1991). In addition to these observations, several reports have demonstrated abnormalities of Ca2+ handling in vascular smooth muscle cells (SMC) of hypertensive animals which, regarding the important role played by Ca2+ in the regulation of vascular tone, could be responsible for marked changes in vessel reactivity (Kwan 1985; Sada et al. 1990). Different observations suggest that voltage-dependent Ca2+ Channels might be altered in vessels from hypertensive rats. The first argument for the implication of a change in Ca2+ Channels in hypertension is the blood pressure-lowering effect of dihydropyridine Ca2+ antagonists (MacGregor et al. 1982; Kazda and Knorr 1990). These antagonists have also been shown to suppress the myogenic active tone displayed by blood vessels from hypertensive rats (Aoki and Asano 1986; Sada et al. 1990).

Keywords

Mesenteric Artery Rest Membrane Potential Aortic Ring Aortic Smooth Muscle Cell Hypertensive Animal 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Agabiti–Rosei E, Muiesan ML, Romanelli G, Beschi M, Castellano M, Muiesan G (1988) Reversal of cardiac hypertrophy by long-term treatment with calcium antagonists in hypertensive patients. J Cardiovasc Pharmacol 12 [Suppl 6]: S75–S78CrossRefGoogle Scholar
  2. Aoki K, Asano M (1986) Effects of Bay K 8644 and nifedipine on femoral arteries of spontaneously hypertensive rats. Br J Pharmacol 88: 221–230PubMedGoogle Scholar
  3. Asano M, Masuzawa K, Matsuda T, Asano T (1988) Reduced function of the stimulatory GTP-binding protein in ß-adrenoceptor-adenylate cyclase system of femoral arteries isolated from spontaneously hypertensive rats. J Pharmacol Exp Ther 246: 709–718PubMedGoogle Scholar
  4. Bodin P, Travo C, Stoclet JC, Travo P (1993) High sensitivity of hypertensive aortic myocytes to norepinephrine and angiotensin. Am J Physiol 264: C441–C445 Boonen HCM, De Mey JGR (1990) Increased calcium sensitivity in isolated resistance arteries from spontaneously hypertensive rats: effects of dihydropyridines. Eur J Pharmacol 179: 403–412Google Scholar
  5. Chai S, Webb RC (1992) Extracellular calcium, contractile activity and membrane potential in tail arteries from genetically hypertensive rats. J Hypertens 10: 1137–1143PubMedCrossRefGoogle Scholar
  6. Chatelain P, Demol D, Roba J (1984) Comparison of [3H]nitrendipine binding to heart membranes of normotensive and spontaneously hypertensive rats. J Cardiovasc Pharmacol 6: 220–223PubMedCrossRefGoogle Scholar
  7. Cheung DW (1984) Membrane potential of vascular smooth muscle and hypertension in spontaneously hypertensive rats. Can J Physiol Pharmacol 62: 957–960PubMedCrossRefGoogle Scholar
  8. Christensen KL, Jespersen LT, Mulvany MJ (1989) Development of blood pressure in spontaneously hypertensive rats after withdrawal of long-term treatment related to vascular structure. J Hypertens 7: 83–90PubMedCrossRefGoogle Scholar
  9. Egleme C, Godfraind T, Miller RC (1984) Enhanced responsiveness of rat isolated aorta to Clonidine after removal of the endothelial cells. Br J Pharmacol 81: 16–18PubMedGoogle Scholar
  10. Ferrante F, Amenta F (1991) Effect of long-term isradipine treatment on the hypertension- dependent changes in coronary arteries in spontaneously hypertensive rats. Drugs Exp Clin Res 17: 363–370PubMedGoogle Scholar
  11. Fujii K, Tominaga F, Ohmori S, Kobayashi K, Koga T, Takata Y, Fujishima M (1992) Decreased endothelium-dependent hyperpolarization to acetylcholine in smooth muscle of the mesenteric artery of spontaneously hypertensive rats. Circ Res 70: 660–669PubMedGoogle Scholar
  12. Galletti F, Rutledge A, Krogh V, Triggle DJ (1991) Age related changes in Ca2+ Channels in spontaneously hypertensive rats. Gen Pharmacol 22: 173–176PubMedCrossRefGoogle Scholar
  13. Godfraind T, Egleme C, AI Osachie I (1985) Role of endothelium in the contractile response of rat aorta to a–adrenoceptors agonists. Clin Sei 68 [Suppl 10]: 65s–71sGoogle Scholar
  14. Godfraind T, Mennig D, Morel N, Wibo M. (1989) Effect of endothelin-1 on calcium Channel gating by agonists in vascular smooth muscle. J Cardiovasc Pharmacol 13 [Suppl 5]: S112–S117PubMedCrossRefGoogle Scholar
  15. Godfraind T, Kazda S, Wibo, M (1991) Effects of a chronic treatment by nisoldipine, a calcium antagonistic dihydropyridine, on arteries of spontaneously hypertensive rats. Circ Res 68: 674–682PubMedGoogle Scholar
  16. Hermsmeyer K (1976) Electrogenesis of increased norepinephrine sensitivity of arterial vascular muscle in hypertension. Circ Res 38: 362–367PubMedGoogle Scholar
  17. Hess P, Lansman JB, Tsien RW (1984) Different modes of Ca Channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature 311: 538–544PubMedCrossRefGoogle Scholar
  18. Holloway ET, Bohr DF (1973) Reactivity of vascular smooth muscle in hypertensive rats. Circ Res 33: 678–685PubMedGoogle Scholar
  19. Ihara M, Noguchi K, Saeki T, Fukuroda T, Tsuchida S, Kimura S, Fukami T, Ishikawa K, Nishikibe M, Yano M (1992) Biological profiles of highly potent novel endothelin antagonists selective for the ETA receptor. Life Sei 50: 247–255CrossRefGoogle Scholar
  20. Ishii K, Kano T, Kurobe Y, Ando J (1983) Binding of [3H] nitrendipine to heart and brain membranes from normotensive and spontaneously hypertensive rats. Eur J Pharmacol 88: 277–278PubMedCrossRefGoogle Scholar
  21. Johnson MD, Wand HY, Ciechanowski D, Friedman E (1991) Reduced G–protein function in desensitized rat aorta. J Pharmacol Exp Ther 259: 255–259PubMedGoogle Scholar
  22. Jones AW (1973) Altered ion transport in vascular smooth muscle from spontaneously hypertensive rats: influence of aldosterone, norepinephrine and angiotensin. Circ Res 33: 563–572PubMedGoogle Scholar
  23. Jones AW (1974) Reactivity of ion fluxes in rat aorta during hypertension and circulatory control. Fed Proc 33: 133–137PubMedGoogle Scholar
  24. Kazda S, Knorr A (1990) Calcium antagonists. In: Ganten D, Mulrow PJ (eds) Pharmacology of anti-hypertensive therapeutics. Springer, Berlin Heidelberg New York, pp 301–375Google Scholar
  25. Kazda S, Garthoff B, Knorr A (1985) Interference of the calcium antagonist nisoldipine with the abnormal response of vessels from hypertensive rats to α-adrenergic Stimulation. J Cardiovasc Pharmacol 7 [Suppl 6]: S61–S65PubMedCrossRefGoogle Scholar
  26. Krippeit–Drews P, Morel N, Godfraind T (1992) Effect of nitric oxide on membrane Potential and contraction of rat aorta. J Cardiovasc Pharmacol 20 [Suppl 12]: S72–S75Google Scholar
  27. Kuriyama H, Suzuki H (1978) Electrical property and chemical sensitivity of vascular smooth muscles in normotensive and spontaneously hypertensive rats. J Physiol (Lond) 285: 409–424Google Scholar
  28. Kwan CY (1985) Dysfunction of calcium handling by smooth muscle in hypertension. Can J Physiol Pharmacol 63: 366–374PubMedCrossRefGoogle Scholar
  29. Lamb FS, Webb RC (1989) Regenerative electrical activity and arterial contraction in hypertensive rats. Hypertension 13: 70–76PubMedGoogle Scholar
  30. Lariviere R, Day R, Schiffrin EL (1993) Increased expression of endothelin-1 gene in blood vessels of deoxycorticosterone acetate–salt hypertensive rats. Hypertension 21: 916–920PubMedGoogle Scholar
  31. Lüscher TF, Vanhoutte PM (1986) Endothelium–dependent contraction to acetylcholine in the aorta from spontaneously hypertensive rat. Hypertension 8: 344–348PubMedGoogle Scholar
  32. Lüscher TF, Boulanger CM, Dohi Y, Yang Z (1992) Endothelium-derived contracting factors. Hypertension 19: 117–130PubMedGoogle Scholar
  33. MacGregor GA, Rotellar C, Markandu ND, Smith SJ, Saguella GA (1982) Contrasting effects of nifedipine, Captopril and propranolol in normotensive and hypertensive subjects. J Cardiovasc Pharmacol 4: S358–S362PubMedCrossRefGoogle Scholar
  34. Morel N, Godfraind T (1991) Characterization in rat aorta of the binding sites responsible for blockade of noradrenaline-evoked calcium entry and contraction by nisoldipine. Br J Pharmacol 102: 467–477PubMedGoogle Scholar
  35. Mülsch A, Busse R (1990) NG-nitro-L-arginine ( NG-[imino(nitroamino)methyl]-L-ornithine) impairs endothelium-dependent dilations by inhibiting cytosolic nitric oxide synthesis from L-arginine. Naunyn Schmiedebergs Arch Pharmacol 341: 143–147Google Scholar
  36. Nayler WG (1988) The effect of amlodipine on hypertension-induced cardiac hypertrophy and reperfusion–induced calcium overload. J Cardiovasc Pharmacol 12 [Suppl 7]: S41–S44CrossRefGoogle Scholar
  37. Nishikibe M, Tsuchida S, Okada M, Fukuroda T, Shimamoto K, Yano M, Ishikawa K, Ikemoto F (1993) Antihypertensive effect of a newly synthesized endothelin antagonist, BQ-123, in a genetic hypertensive model. Life Sei 52: 717–724CrossRefGoogle Scholar
  38. Nyborg NCB, Bevan JA (1988) Increased a–adrenergic receptor affinity in resistance vessels from hypertensive rats. Hypertension 11: 635–638PubMedGoogle Scholar
  39. Sada T, Koike H, Ikeda M, Sato K, Ozaki H, Karaki H (1990) Cytosolic free calcium of aorta in hypertensive rats. Chronic inhibition of angiotensin Converting enzyme. Hypertension 16: 245–251Google Scholar
  40. Storm DS, Stuenkel EL, Webb RC (1992) Calcium Channel activation in arterioles from genetically hypertensive rats. Hypertension 20: 380–388PubMedGoogle Scholar
  41. Thompson LP, Bruner CA, Lamb FS, King CM, Webb RC (1987) Calcium influx and vascular reactivity in systemic hypertension. Am J Cardiol 59: 29A–34APubMedCrossRefGoogle Scholar
  42. Tomobe Y, Ishikawa T, Yanagisawa M, Kimura S, Masaki T, Goto K (1991) Mechanisms of altered sensitivity to endothelin-1 between aortic smooth muscles of spontaneously hypertensive and Wistar-Kyoto rats. J Pharmacol Exp Ther 257: 555–561PubMedGoogle Scholar
  43. Van de Voorde J, Vanheel B, Leusen I (1992) Endothelium-dependent relaxation and hyperpolarization in aorta from control and renal hypertensive rats. Circ Res 70: 1–8Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • Théophile Godfraind
    • 1
  • Nicole Morel
    • 1
  1. 1.Laboratoire de Pharmacologie UCL 5410Université Catholique de LouvainBrusselsBelgium

Personalised recommendations