Inhibitory effects of Hoe 140 on vasodilator responses to bradykinin in the mesenteric vascular bed of the cat

Abstract The effect of Hoe 140, a bradykinin B 2 receptor antagonist, on vasodilator responses to bradykinin was investigated in the mesenteric vascular bed of the cat under constant flow conditions. Injections of bradykinin into the mesenteric vascular bed induced dose-related decreases in perfusion pressure which were reduced significantly following administration of Hoe 140 (D-Arg-[Hyp 3 ,Thi 5 ,D-Tic 7 ,Oic 8 ]bradykinin) (100 μg/kg i.v.). The inhibitory effects of Hoe 140 were longer than 3 h in duration and vasodilator responses to acetylcholine and S-nitroso-N-acetylpenicillamine and vasoconstrictor responses to norepinephrine, angiotensin II, and the thromboxane mimic, U46619 (9,11-dideoxy-11α, 9α-epoxymethano-prostaglandin F 2α ) were unchanged by the B 2 receptor antagonist. Hoe 140 had little effect on baseline systemic arterial and mesenteric arterial perfusion pressures. These results suggest that Hoe 140 is a potent, highly selective, long-acting bradykinin B 2 receptor antagonist with little agonistic activity in the mesenteric vascular bed of the cat.