Role for prazosin in reducing the development of rabbit intimal hyperplasia after endothelial denudation

Abstract

Intimal hyperplasia is the universal response to endothelial denudation and occurs after a variety of vascular procedures. In a proportion of cases the smooth muscle cell proliferation may lead to stenosis of the blood vessels. These vessels exhibit increased sensitivity to noradrenaline that can be reduced by the alpha 1-adrenergic antagonist prazosin. Because the alpha 1-adrenergic receptor and platelet-derived growth factor (which promotes vascular smooth muscle cell proliferation) act through the same metabolic pathway, it was postulated that alpha 1-adrenergic blockade might reduce the development of intimal hyperplasia. Twenty-eight New Zealand White rabbits underwent endothelial denudation of the aorta using a Fogarty balloon catheter. Test rabbits were treated with prazosin from the day of operation until they were killed. All rabbits were killed either 1 or 4 weeks after endothelial denudation. Intimal hyperplasia in cross-sections of the aorta was measured using an X-Y digitizer and was standardized in terms of percentage luminal reduction. Prazosin-treated rabbits had significantly less luminal reduction at 1 week (0.75(1.8) versus 9.7(3.1) per cent, mean (s.d.), P less than 0.001) and at 4 weeks (14.7(4.4) versus 25.3(12.8) per cent, P less than 0.05) than control rabbits. It is concluded that prazosin caused a major reduction in the development of intimal hyperplasia.