Vasoconstrictor and vasodilator effects in normal and atherosclerotic conscious rabbits

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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) 100μgkg−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 100μgkg−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.