EFFECT OF VERAPAMIL ON INTIMAL THICKENING AND VASCULAR REACTIVITY IN THE COLLARED CAROTID-ARTERY OF THE RABBIT

1 Intimal thickening is a common site for atherosclerosis. Therefore, we investigated whether the calcium entry blocker verapamil (10 mg kg( -1) body weight day(-1), s.c.) can retard intimal thickening and chang es in vascular reactivity induced by a non-occlusive, silicone collar positioned around the left carotid artery of rabbits. The contralatera l carotid artery was sham-operated and served as a control. 2 Verapami l and placebo (saline 0.1 ml kg(-1) day(-1), s.c.) treatments were ini tiated 7 days before placing the collar and lasted 3 weeks. Thereafter , segments were cut from collared and sham-treated arteries for histol ogy and isometric tension recording. 3 The intima/media (I/M) ratio in creased after 14 days of collar treatment, but intimal thickening was not inhibited by verapamil (I/M ratio placebo 0.31+/-0.07, verapamil 0 .32+/-0.09). 4 The collar decreased the capacity to develop force, as indicated by the response to a supramaximal concentration of KCl, decr eased the sensitivity (pD(2)) to acetylcholine (ACh) and phenylephrine (Phe), but increased the sensitivity to 5-hydroxytryptamine (5-HT). 5 Although verapamil did not affect intimal thickening, it normalized t he hypersensitivity to 5-HT in collared arteries. 6 The contraction to the supramaximal concentration of KCl was not affected by verapamil. Verapamil decreased the E(max) of ACh, but this was only seen in colla r-treated arteries. Verapamil also decreased the sensitivity to ACh an d Phe, in both sham- and collar-treated arteries. 7 We conclude that v erapamil, without preventing thickening of the intima, can modify coll ar-induced changes in vascular reactivity.