EFFECTS OF THE COMBINED ET(A) AND ET(B) RECEPTOR ANTAGONIST PD145065 ON ARTERIES, ARTERIOLES, AND VEINS IN THE CAT HINDLIMB

The aim of this study was to describe in quantitative terms the effect s of ET(A) and ET(B) receptor blockade on vascular tone (resistance) i n large-bore arterial resistance vessels (>25 mu m), small arterioles (<25 mu m), and veins in the cat gastrocnemius muscle in vivo. In the muscle vascular bed, the combined ET(A) and ET(B) receptor antagonist PD145065 (1 mg/kg/min, intra-arterially) abolished the biphasic vascul ar responses (dilatation followed by constriction) to both ET-1 (0.4 m u g/kg/min, intraarterially) and to the selective ET(B) receptor agoni st IRL1620 (3.2 mu g/kg/min, intra-arterially). In the cat femoral art ery and vein in vitro, PD145065 competitively inhibited the contractil e responses to both ET-1 and IRL1620. The contractile response to the latter agonist could be evoked only after long-term incubation of the vessels (37 degrees C for 5 days). These results indicate that PD14506 5 is a potent antagonist at both ET(A) and ET(B) receptors in vivo and in vitro. Therefore, this antagonist may prove useful for elucidating the possible physiologic and/or pathophysiologic roles of the endothe lins. For example, it was shown that PD145065 had no effect on vascula r tone in the resting state, indicating no role for the endothelins in the regulation of basal vascular tone in cat skeletal muscle.