Influence of atherosclerosis on vascular responsiveness in isolated rabbit vascular smooth muscle

Coronary arteries and aortic rings were isolated from rabbits fed either a control diet or a high cholesterol (1 to 2%) diet for 8 to 11 weeks and studied for their vasoactive properties to a variety of vasoconstrictor and vasodilator agents. Perfused coronary arteries without intact endothelium constrict markedly to a thromboxane A2 agonist (i.e., carbocyclic thromboxane A2, CTA2) and dilate markedly to iloprost, a prostacyclin analog. No differences occurred between the coronary arteries isolated from control or atherosclerotic rabbits. Additional studies were conducted on rabbit aortic vascular smooth muscle rings containing functionally intact endothelium and in rings denuded of their endothelium. Acetylcholine (20 to 2000 ng/ml) neither constricted nor dilated control aortic rings without endothelium, and markedly dilated aortic rings with intact endothelium in a concentration dependent manner. In atherosclerotic aortic rings, acetylcholine constricted preparations without endothelium, and dilated rings with endothelium to a much lesser extent than that observed in control rings. Similar reductions in responsiveness occurred with adenosine diphosphate (ADP), another endothelium-dependent vasodilator, but not with iloprost, a nonendothelium-dependent dilator. No differences were observed in constrictor responses to norepinephrine. Aortae from atherosclerotic rabbits produced less prostacyclin in response to arachidonic acid than control aortae. These data point to an important role of the endothelium in modulating the vascular response to vasodilators in atherosclerotic rabbit arterial vessels.