PHARMACOLOGY OF KININS IN THE ARTERIAL AND VENOUS MESENTERIC BED OF NORMAL AND B-2 KNOCKOUT TRANSGENIC MICE

We have tested the vasoactive effects of kinins in addition to various other endothelium-dependent or independent agonists in the arterial a nd venous perfused mesenteric circuits of the mouse. Bradykinin (0.1 p mol-100 nmol), but not des-Arg(9)-bradykinin (10 nmol) induced a dose- dependent vasodilation of the precontracted arterial and venous mesent eric vasculature of the mouse. Furthermore, acetylcholine (2.5 nmol) a lso induced a marked arterial vasodilation but was without effect on t he venous side. Other endothelium-dependent vasodilators, such as plat elet-activating factor (PAF) (1 nmol), tachykinin NK1 selective agonis t ([Sar(9),Met(O-2)(11)]substance P) (0.5 nmol) and adenosine diphosph ate (5 nmol), were without effect on either side of the mesenteric bed of the mouse. The bradykinin B-2 receptor selective antagonist (HOE 1 40) abolished the arterial and venous vasodilation induced by bradykin in without affecting that of acetylcholine or sodium nitroprusside. In addition, the bradykinin B-1 receptor antagonist des-Arg(9)-[Leu(8)]b radykinin was without effect on the responses induced by bradykinin. A nitric oxide synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) markedly reduced, whereas removal of the endothelium with 3- [3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS) abolis hed dilatation to bradykinin and acetylcholine (arterial side only) wi thout affecting that induced by sodium nitroprusside in the mouse arte rial and venous mesenteric circuits. In the same two circuits of trans genic B-2 knockout mice, the vasodilatory responses to bradykinin were absent, whereas the arterial circuit still responded to acetylcholine by a L-NAME-sensitive vasodilation. Our results suggest the exclusive contribution of B-2 receptors located on the endothelium in the vasod ilatory effects of bradykinin in the arterial and venous mesenteric ci rcuits of the mouse. (C) 1997 Elsevier Science B.V.