CHARACTERIZATION OF RECEPTORS FOR KININS AND NEUROKININS IN THE ARTERIAL AND VENOUS MESENTERIC VASCULATURES OF THE GUINEA-PIG

1 In the present work, we have studied the microvascular reactivity of the arterial and venous mesenteric beds of the guinea-pig to bradykinin, neurokinins and other agents. 2 The vasoactive properties of three selective agonists for neurokinin receptors, namely [Sar(9),Met (O-2)(11)]SP (NK1), [beta-Ala(8)]NKA(4-10) (NK2) and [MePhe(7)]NKB (NK3), were evaluated on precontracted arterial and venous mesenteric vasculatures of the guinea-pig. The NK1-selective agonist, [Sar(9),Met(O-2)(11)]SP (1 to 1000 pmol), induced an endothelium-dependent and N-omega-nitro-L-arginine methyl ester (L-NAME)-sensitive relaxation of the arterial vasculature precontracted with methoxamine, whereas the NK2 and NK3-selective agonists were virtually inactive at high doses (1000 pmol). 3 The three selective neurokinin receptor agonists were inactive in the non-precontracted arterial and venous mesenteric vasculatures as well as in the precontracted venous mesenteric vasculature. 4 Bradykinin (0.1 to 100 pmol) induced a marked dose- and endothelium-dependent vasodilatation of the precontracted arterial and venous vasculatures. ED(50) values were 5.5 pmol on the arterial side and 1.9 pmol on the venous side. In contrast, desArg(9)-bradykinin was inactive at doses up to 1000 pmol. Furthermore, on the arterial and venous sides, a higher dose of bradykinin (1000 pmol), induced a biphasic effect, a transient constriction followed by a marked and sustained vasodilatation. The vasodilator effects of bradykinin were abolished by Hoe 140 (0.1 mu M) and CHAPS, markedly reduced by L-NAME and were unaffected by [Leu(8)]desArg(9)-bradykinin (0.1 mu M) On both sides of the mesenteric vasculature. Hoe 140 also abolished the arterial vasoconstrictions induced by high doses of bradykinin. 5 Noradrenaline, angiotensin II and endothelin-l produced contractions on both sides of the mesenteric circulation, while acetylcholine (arterial side) and sodium nitroprusside (arterial and venous sides) caused vasodilatation. 6 Our study supports the view that NK1 receptors responsible for vasodilatation are present solely in the endothelium of the arterial mesenteric vasculature of the guinea-pig. On the other hand, bradykinin (0.1 to 100 pmol) exerts predominantly vasodilator effects on both sides of the mesenteric vasculature via selective activation of B-2 receptors located on the endothelium. The same receptor type located on the smooth muscle appears to be responsible for the arterial and venous constriction with high doses of bradykinin.