Vasoconstrictor and vasodilator effects in normal and atherosclerotic conscious rabbits

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 (All), were obtained in 6 cholesterol-fed and 6 control rabbits before and after isradipine (code name PN200-110) 100 yg kg-. 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 All were enhanced in atherosclerotic compared with normal rabbits.4 After a dose of lOOpgkg'-isradipine the dose-response curves of all agents were shifted to the right. The differences between atherosclerotic and control rabbits disappeared, except for the Allinduced pressor response, which remained enhanced in atherosclerotic animals. The calcium antagonist thus only partly corrected the atherosclerosis-associated hyperresponsiveness to vasoconstrictor agents.

Vascular Response to Angiotensin II in Atherosclerosis

“…In vivo studies are also difficult to reconcile. For example, Hof and Hof 11 describe an enhanced pressure effect of systemically administered Ang II, while Carroll et al 10 found that both the systemic pressure response and the renal vasoconstrictor response to intrarenal Ang II infusions were similar in control and atherosclerotic rabbits. This diversity within the literature prompted us to test whether the overall vascular responsiveness to Ang II is enhanced in atherosclerosis and whether an impairment of cardiovascular control mechanisms adds to this hyperresponsiveness.…”

“…Despite the nonuniform responses to Ang II found in isolated vessels, 3,9 the effect of Ang II on arterial blood pressure was enhanced in atherosclerotic conscious rabbits. 11 Total peripheral resistance was not determined in the latter study; thus, it remains unclear whether this larger pressure increase relies on an enhanced vascular responsiveness. Alternatively, blood pressure controlling mechanisms, eg, the arterial baroreceptor reflex, could be altered in animals maintained on a high-cholesterol diet and, therefore, may be responsible for the larger pressure response to Ang II in intact animals.…”

“…An initial baseline period of 5 minutes was followed by an intravenous infusion of 0.4 g ⅐ kg Ϫ1 ⅐ min Ϫ1 Ang II. This dose was selected on the basis of both the literature 11,14 and pilot experiments in which we applied doses in the range of 0.4 to 4.…”

Inhibition of cyclic AMP- and cyclic GMP-mediated dilations in isolated arteries by oxidized low density lipoproteins.

“…31 " 33 Reduction of cGMP and cAMP levels, as described in this study, may also contribute to this phenomenon. A decreased level of tissue cyclic nucleotides could render arteries more sensitive to contractile agonists 34 - 35 and also could explain the potentiation of contractile responses by Ox-LDL in vitro.…”

Effect of dietary ethanol on atherosclerosis in rabbits

“…It has been demonstrated by in vivo experiments with rabbits and dogs, that high levels of plasma low-density lipoprotein cholesterol potentiate aj-adrenergic vasoconstriction (Bloom et al, 1975;Hof and Hof, 1988). An increase in the number of a,-adrenergic receptors has also been observed in atherosclerotic rabbit aortas (Nanda and Henry, 1980).…”