INHIBITORY EFFECTS OF HOE-140 ON VASODILATOR RESPONSES TO BRADYKININ IN THE MESENTERIC VASCULAR BED OF THE CAT

The effect of Hoe 140, a bradykinin B2 receptor antagonist, on vasodil ator responses to bradykinin was investigated in the mesenteric vascul ar bed of the cat under constant flow conditions. Injections of bradyk inin into the mesenteric vascular bed induced dose-related decreases i n perfusion pressure which were reduced significantly following admini stration of Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin) (100 mug /kg i.v.). The inhibitory effects of Hoe 140 were longer than 3 h in d uration and vasodilator responses to acetylcholine and S-nitroso-N-ace tylpenicillamine and vasoconstrictor responses to norepinephrine, angi otensin II, and the thromboxane mimic, U46619 -dideoxy-11alpha,9alpha- epoxymethano-prostaglandin F2alpha) were unchanged by the B2 receptor antagonist. Hoe 140 had little effect on baseline systemic arterial an d mesenteric arterial perfusion pressures. These results suggest that Hoe 140 is a potent, highly selective, long-acting bradykinin B2 recep tor antagonist with little agonistic activity in the mesenteric vascul ar bed of the cat.