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. 1988 Dec;95(4):1075–1080. doi: 10.1111/j.1476-5381.1988.tb11741.x

Vasoconstrictor and vasodilator effects in normal and atherosclerotic conscious rabbits.

R P Hof 1, A Hof 1
PMCID: PMC1854274  PMID: 2975523

Abstract

1. Rabbits were fed a cholesterol-rich diet for 5 two-week intervals. Polyvinyl catheters were then implanted into the femoral artery and vein. Dose-response curves to acetylcholine (ACh), noradrenaline (NA), phenylephrine (Phen) and angiotensin II (AII), were obtained in 6 cholesterol-fed and 6 control rabbits before and after isradipine (code name PN200-110) 100 micrograms kg-1. After these experiments the animals were killed and aortic rings were suspended in an organ bath. ACh but not nitroprusside-induced relaxation was impaired in atherosclerotic but not in control preparations. 2. ACh decreased blood pressure dose-dependently in both groups of rabbits even though ACh did not relax the aortae of the same rabbits in vitro. 3. Blood pressure effects reflect mostly changes in resistance vessels. The pressor effects of NA, Phen and AII were enhanced in atherosclerotic compared with normal rabbits. 4. After a dose of 100 micrograms kg-1 isradipine the dose-response curves of all agents were shifted to the right. The differences between atherosclerotic and control rabbits disappeared, except for the AII-induced pressor response, which remained enhanced in atherosclerotic animals. The calcium antagonist thus only partly corrected the atherosclerosis-associated hyperresponsiveness to vasoconstrictor agents.

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Selected References

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  1. Bossaller C., Habib G. B., Yamamoto H., Williams C., Wells S., Henry P. D. Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. J Clin Invest. 1987 Jan;79(1):170–174. doi: 10.1172/JCI112779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bossaller C., Yamamoto H., Lichtlen P. R., Henry P. D. Impaired cholinergic vasodilation in the cholesterol-fed rabbit in vivo. Basic Res Cardiol. 1987 Jul-Aug;82(4):396–404. doi: 10.1007/BF01907027. [DOI] [PubMed] [Google Scholar]
  3. Cauvin C., Loutzenhiser R., Van Breemen C. Mechanisms of calcium antagonist-induced vasodilation. Annu Rev Pharmacol Toxicol. 1983;23:373–396. doi: 10.1146/annurev.pa.23.040183.002105. [DOI] [PubMed] [Google Scholar]
  4. Freiman P. C., Mitchell G. G., Heistad D. D., Armstrong M. L., Harrison D. G. Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primates. Circ Res. 1986 Jun;58(6):783–789. doi: 10.1161/01.res.58.6.783. [DOI] [PubMed] [Google Scholar]
  5. Ginsburg R., Bristow M. R., Davis K., Dibiase A., Billingham M. E. Quantitative pharmacologic responses of normal and atherosclerotic isolated human epicardial coronary arteries. Circulation. 1984 Feb;69(2):430–440. doi: 10.1161/01.cir.69.2.430. [DOI] [PubMed] [Google Scholar]
  6. Habib J. B., Bossaller C., Wells S., Williams C., Morrisett J. D., Henry P. D. Preservation of endothelium-dependent vascular relaxation in cholesterol-fed rabbit by treatment with the calcium blocker PN 200110. Circ Res. 1986 Feb;58(2):305–309. doi: 10.1161/01.res.58.2.305. [DOI] [PubMed] [Google Scholar]
  7. Heistad D. D., Armstrong M. L., Marcus M. L., Piegors D. J., Mark A. L. Augmented responses to vasoconstrictor stimuli in hypercholesterolemic and atherosclerotic monkeys. Circ Res. 1984 Jun;54(6):711–718. doi: 10.1161/01.res.54.6.711. [DOI] [PubMed] [Google Scholar]
  8. Henry P. D., Yokoyama M. Supersensitivity of atherosclerotic rabbit aorta to ergonovine. Mediation by a serotonergic mechanism. J Clin Invest. 1980 Aug;66(2):306–313. doi: 10.1172/JCI109858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hof R. P. Calcium antagonists, vasoconstrictors and the peripheral circulation. Gen Pharmacol. 1987;18(5):459–466. doi: 10.1016/0306-3623(87)90063-2. [DOI] [PubMed] [Google Scholar]
  10. Hof R. P. Interaction between two calcium antagonists and two beta blockers in conscious rabbits: hemodynamic consequences of differing cardiodepressant properties. Am J Cardiol. 1987 Jan 30;59(3):43B–51B. doi: 10.1016/0002-9149(87)90081-6. [DOI] [PubMed] [Google Scholar]
  11. Hof R. P., Salzmann R., Siegl H. Selective effects of PN 200-110 (isradipine) on the peripheral circulation and the heart. Am J Cardiol. 1987 Jan 30;59(3):30B–36B. doi: 10.1016/0002-9149(87)90079-8. [DOI] [PubMed] [Google Scholar]
  12. Hof R. P., Scholtysik G. Effects of the calcium antagonist PY 108-068 on myocardial tissues in vitro and on reflex tachycardia in vivo. J Cardiovasc Pharmacol. 1983 Mar-Apr;5(2):176–183. doi: 10.1097/00005344-198303000-00002. [DOI] [PubMed] [Google Scholar]
  13. Jayakody L., Senaratne M., Thomson A., Kappagoda T. Endothelium-dependent relaxation in experimental atherosclerosis in the rabbit. Circ Res. 1987 Feb;60(2):251–264. doi: 10.1161/01.res.60.2.251. [DOI] [PubMed] [Google Scholar]
  14. Jayakody R. L., Kappagoda C. T., Senaratne M. P., Sreeharan N. Absence of effect of calcium antagonists on endothelium-dependent relaxation in rabbit aorta. Br J Pharmacol. 1987 May;91(1):155–164. doi: 10.1111/j.1476-5381.1987.tb08994.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kawachi Y., Tomoike H., Maruoka Y., Kikuchi Y., Araki H., Ishii Y., Tanaka K., Nakamura M. Selective hypercontraction caused by ergonovine in the canine coronary artery under conditions of induced atherosclerosis. Circulation. 1984 Feb;69(2):441–450. doi: 10.1161/01.cir.69.2.441. [DOI] [PubMed] [Google Scholar]
  16. Ludmer P. L., Selwyn A. P., Shook T. L., Wayne R. R., Mudge G. H., Alexander R. W., Ganz P. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986 Oct 23;315(17):1046–1051. doi: 10.1056/NEJM198610233151702. [DOI] [PubMed] [Google Scholar]
  17. Lüscher T. F., Vanhoutte P. M. Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat. Hypertension. 1986 Apr;8(4):344–348. doi: 10.1161/01.hyp.8.4.344. [DOI] [PubMed] [Google Scholar]
  18. Rosendorff C., Hoffman J. I., Verrier E. D., Rouleau J., Boerboom L. E. Cholesterol potentiates the coronary artery response to norepinephrine in anesthetized and conscious dogs. Circ Res. 1981 Mar;48(3):320–329. doi: 10.1161/01.res.48.3.320. [DOI] [PubMed] [Google Scholar]
  19. Shimokawa H., Aarhus L. L., Vanhoutte P. M. Porcine coronary arteries with regenerated endothelium have a reduced endothelium-dependent responsiveness to aggregating platelets and serotonin. Circ Res. 1987 Aug;61(2):256–270. doi: 10.1161/01.res.61.2.256. [DOI] [PubMed] [Google Scholar]
  20. Shimokawa H., Tomoike H., Nabeyama S., Yamamoto H., Araki H., Nakamura M., Ishii Y., Tanaka K. Coronary artery spasm induced in atherosclerotic miniature swine. Science. 1983 Aug 5;221(4610):560–562. doi: 10.1126/science.6408736. [DOI] [PubMed] [Google Scholar]
  21. Vanhoutte P. M. Endothelium-dependent contractions in arteries and veins. Blood Vessels. 1987;24(3):141–144. doi: 10.1159/000158688. [DOI] [PubMed] [Google Scholar]
  22. Verbeuren T. J., Jordaens F. H., Zonnekeyn L. L., Van Hove C. E., Coene M. C., Herman A. G. Effect of hypercholesterolemia on vascular reactivity in the rabbit. I. Endothelium-dependent and endothelium-independent contractions and relaxations in isolated arteries of control and hypercholesterolemic rabbits. Circ Res. 1986 Apr;58(4):552–564. doi: 10.1161/01.res.58.4.552. [DOI] [PubMed] [Google Scholar]
  23. Wright C. E., Angus J. A. Effects of hypertension and hypercholesterolemia on vasodilatation in the rabbit. Hypertension. 1986 May;8(5):361–371. doi: 10.1161/01.hyp.8.5.361. [DOI] [PubMed] [Google Scholar]
  24. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411–415. doi: 10.1038/332411a0. [DOI] [PubMed] [Google Scholar]

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