Hypercholesterolemia and atherosclerosis change vascular reactivity in rabbits by different mechanisms.

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Abstract
Vasomotor reactivity was assessed in vitro in arterial segments obtained from rabbits with different stages of atherosclerosis. Rabbits were fed a standard chow diet (controls) or a cholesterol-enriched diet to induce hypercholesterolemia and atherosclerosis. A third group received the hydroxymethylglutaryl coenzyme A reductase inhibitor, lovastatin, simultaneously with the cholesterol diet. Contractile responses of thoracic aortas to norepinephrine, serotonin, and potassium-rich solution, as well as endothelium-dependent dilations to acetylcholine, were compared after 2 and 4 months on the respective diet. Additionally, plasma cholesterol levels and the amount of plaques covering the intimal surface (as a percentage of the intimal surface) were determined; transmission electron microscopy of atherosclerotic arteries was also performed. After 2 months, the only difference was an enhancement of contractile responses to serotonin in the cholesterol-fed versus the control group. After 4 months on the diet, contractile responses to serotonin were further enhanced, and norepinephrine- and potassium-induced vasoconstrictions were now also significantly enhanced in cholesterol-fed animals versus controls. Endothelium-dependent vasodilations were simultaneously reduced in cholesterol-fed animals. These alterations were partly prevented in cholesterol-fed and lovastatin-treated animals. Suppression of nitric oxide synthesis in control aortas by NG-nitro-L-arginine did not reveal any significant increases in contractile responses. Contractile responses to serotonin were enhanced after 2 months on the diet but before the appearance of intimal plaques, whereas attenuation of endothelium-dependent dilations, as well as the further enhancement of contractile responses to serotonin and to other agonists, were closely correlated with the degree of intimal plaques after 4 months on the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

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