Impaired cholinergic vasodilation in the cholesterol-fed rabbit in vivo

Endothelium-dependent cholinergic relaxation in vitro is impaired in large arteries of animals and man with atherosclerosis. To assess the physiological importance of this impairment, we compared vasodilator effects of acetylcholine and nitroprusside, an endothelium-independent agent, in control rabbits (n = 12) and rabbits fed a 1% cholesterol diet for 10 weeks (n = 8). The hindlimb of the rabbits was perfused via an extracorporal loop at a constant flow, and perfusion pressure was used as an index of total vascular resistance. The hindlimb vascular resistance was monitored during intraarterial bolus injections with graded concentrations of acetylcholine (0.01-1.000 ng) and nitroprusside (0.1-1.000 ng) which produced no change in systemic hemodynamics. Between 0.1 and 1.000 ng nitroprusside, resistance changes in control and cholesterol-fed rabbits were virtually identical. In contrast, the resistance change induced by acetylcholine was significantly suppressed in cholesterol-fed rabbits over a wide range of concentrations (1.0-1.000 ng; p less than 0.05). The results indicate that in a model of atherosclerosis there is a reduced vasodilatory responsiveness to the endothelium-dependent acetylcholine, whereas the effect of the endothelium-independent nitroprusside is fully preserved.