ACTION OF PROBUCOL IN ARTERIES FROM NORMAL AND HYPERCHOLESTEROLEMIC RABBITS

1 The effect of probucol on the vascular reactivity of different arter ies isolated from rabbits was studied as well as its effects on the de velopment of atherosclerosis in a cholesterol-fed rabbit model. 2 Prob ucol 10(-6)-5 x 10(-4) M produced a concentration-dependent inhibition of the contractile responses induced by KCl (80 mM), the sequence for the IC50 was: mesenteric artery (5(th) branch, 4.8+/-2.6 x 10(-5) M) >aorta (8.2+/-2.3 x 10(-5) M) >femoral artery (>5 x 10(-4) M). The res ponse to noradrenaline was: mesenteric artery (5(th) branch, 4.2+/-1.3 x 10(-5) M) >aorta (3.2+/-3.0 x 10(-4) M) >femoral (>5 x 10(-4) M). 3 In the aorta, probucol (10(-5)-10(-4) M) shifted the concentration-re sponse curves to Ca2+ downward and to the right. 4 Probucol at 5 x 10( -5) M and 5 x 10(-4) M showed a reduction in the Ca-45(2+) uptake in r esting, nonstimulated aortic rings as well as the uptake induced by bo th noradrenaline 10(-6) M and KCl 80 mM. 5 In experiments in vivo, pro bucol did not affect lipid profiles; however, drug-treatment significa ntly decreased the cholesterol content of aortic tissue and the extent of intimal surface covered with atherosclerotic lesions. 6 The vascul ar reactivity was recovered in femoral arteries from rabbits on the at herogenic diet plus probucol. 7 It is concluded that the effect of pro bucol in vascular smooth muscle can be attributed to an inhibition of Ca2+ entry through both potential- and receptor-operated pathways. Mor eover our findings suggest that the effects of probucol on movement of calcium in vascular smooth muscle may play an important role in the m echanism of antiatherogenic properties of this drug.