Vascular action of bradykinin is mediated by B₂-subtype receptors in the canine lingual artery

Abstract

The mechanisms underlying the responses of the canine lingual artery to bradykinin (BK) have been examined. In endothelium-intact lingual artery ring preparations contracted to a stable plateau tension by the addition of norepinephrine (NE), BK produced B2-receptor antagonist [D-Phe⁷]-BK-sensitive and endothelium-dependent relaxations. Theobserved effect was significantly inhibited by nitric oxide (NO) inactivator hemoglobin, methylene blue, a good inhibitor of soluble guanylate cyclase, and by N^G-monomethyl-L-arginine, a NO synthase inhibitor, but not by B₁-receptor antagonist des-Arg⁹-[Leu⁸]-BK, suggesting endothelial production of the vasodilator agent NO by B₂-receptors activation. In endotheliumdenuded rings in the absence of active tension caused by NE, BK increased muscle tension and cytosolic Ca²⁺ level; these were inhibited by [D-Phe⁷]-BK. The concentration-dependent contraction produced by BK of endothelium-denuded rings was also attenuated by [D-Phe⁷]-BK; protein kinase C inhibitor H-7 and phospholipase C inhibitor neomycin B reduced the BK-induced contraction. Indomethacin was without effect. Hence, it can be concluded that BK can cause relaxation and contraction in the canine lingual artery via B₂-receptors activation. The relaxation response to BK might be mediated by endothelial production of No.BK has the potential to be a vasoconstrictor by exerting an effect on vascular smooth muscle cells, but not on endothelial cells, via B₂-receptors activation. It is also postulated that the contractile response to BK may be due to the production of second messengers derived from the action of phospholipase C, but not due to contractile prostanoids, when B₂-receptors are activated.