Modulation of vascular reactivity by vasoactive peptides in aortic rings from hypercholesterolemic rabbits.

The effect of moderate elevation in serum cholesterol on vascular reactivity to epidermal growth factor (EGF), endothelin (ET-1) and thrombin, vasoactive peptides present at sites of vascular injury, was examined in isolated aortic rings from rabbits fed either a casein-rich or a control diet for 10-12 weeks. In rings from hypercholesterolemic rabbits, development of maximal isometric tension to all peptide agonists was increased 22 +/- 0.6% while the EC50 for contraction was decreased. Vasorelaxant responses to nitroprusside, an endothelium-independent dilator, were largely intact, while those to A231897, an endothelium-dependent agent, were attenuated. These data suggest that elevation in serum cholesterol in the absence of atherosclerotic lesions is sufficient to increase vascular reactivity to peptide vasoactive mediators, an effect which may predispose arteries to vasospasm.