Bradykinin-induced contractions of canine saphenous veins: Mediation by B-2 receptors and involvement of eicosanoids

1 Experiments were designed to determine the subtype of kinin-receptors mediating the contraction of venous smooth muscle to bradykinin and to investigate the involvement of metabolites of arachidonic acid in this response. 2 Bradykinin (10(-9) to 10(-6) M) caused concentration-dependent contractions of the canine isolated saphenous vein without endothelium, which were potentiated by indomethacin (10(-5) M, an inhibitor of cyclo-oxygenase). The concentration-response curve was biphasic, reaching an asymptote at 10(-8) M and a secondary maximal response at 10(-6) M. 3 Bradykinin (10(-8) M to 3 x 10(-6) M) caused a three fold stimulation in the release of the vasodilator prostaglandin E(2) (PGE(2)) and a two fold stimulation of that of the vasodilator prostacyclin, measured by the production of 6-keto-PGF(1 alpha) (its stable breakdown product). 4 Under control conditions, nordihydroguaiaretic acid (NDGA, 10(-5) M), an inhibitor of lipoxygenase, did not affect the response to bradykinin. In the presence of indomethacin (10(-5) M), NDGA reduced contractions to bradykinin, suggesting the involvement of lipoxygenase metabolites in the potentiation evoked by the inhibitor of cyclo-oxygenase. 5 The selective B-1 receptor agonist [des-Arg(9)]-bradykinin, in the concentration-range 10(-6) to 10(-5) M, induced contractions, which were abolished by the B-2 receptor antagonist D-Arg-[Hyp(3),Thi(5),D-Tic(7),Oic(8)]- bradykinin (Hoe 140, 10(-6) M). The selective beta(1) receptor antagonist [des-Arg(9),Leu(8)]-bradykinin, (10(-7) to 10(-5) M) had no significant effect on bradykinin-induced contractions. 6 The beta(2) receptor antagonists Hoe 140 (10(-8) to 10(-6) M) and D-Arg[Hyp(3),D-Phe(7)]-bradykinin (10(-7) to 10(-5) M) shifted the concentration-response curve to bradykinin to the right in a concentration-dependent manner. 7 These results indicate that, in the canine saphenous vein, bradykinin causes contraction by activating beta(2) receptors. This results in the production of metabolites of arachidonic acid, which play a key role in the contraction of canine saphenous venous smooth muscle.