Influence of HOE 140, A Bradykinin Receptor Antagonist, in the Isolated Mesenteric Vascular Bed of the Rat.

The inhibitory effects of HOE 140 (D-Arg-[Hyp(3),Thi(5),D-Tic(7), Oic(8)]bradykinin), a novel bradykinin B(2)-receptor antagonist, on mesenteric vascular bed vasodilator responses to bradykinin (BK) were investigated under constant-flow conditions in the isolated blood-perfused rat mesenteric vascular bed. During baseline conditions, injections of BK produced dose-related decreases in mesenteric arterial perfusion pressure which were reproducible with respect to time. HOE 140, in a dose of 50 &mgr;g/kg intravenously, decreased vasodilator responses to BK but had no significant effect on mesenteric vasodilator responses to albuterol, acetylcholine, levcromakalim, or to nitroglycerin. These results suggest that BK has significant vasodilator actions which are mediated by the activation of kinin B(2)-receptors in the mesenteric vascular bed of the rat. HOE 140 caused a significant increase in baseline mesenteric arterial perfusion pressure. These data indicate that HOE 140 is a highly selective, BK B(2)-receptor antagonist in the mesenteric vascular bed of the rat, and the elevation of baseline mesenteric arterial tone by HOE 140 suggests that BK plays a role in maintaining normal vascular tone in the mesenteric circulation. These results also suggest that HOE 140 is a useful probe for studying the role of BK in the mesenteric vascular bed under physiologic and pathophysiologic conditions.