Bradykinin-induced contractions of canine saphenous veins: mediation by B2 receptors and involvement of eicosanoids.

Abstract

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 E2 (PGE2) and a two fold stimulation of that of the vasodilator prostacyclin, measured by the production of 6-keto-PGF1 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 B1 receptor agonist [des-Arg9]-bradykinin, in the concentration-range 10(-6) to 10(-5) M, induced contractions, which were abolished by the B2 receptor antagonist D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin (Hoe 140; 10(-6) M). The selective B1 receptor antagonist [des-Arg9, Leu8]-bradykinin, (10(-7) to 10(-5) M) had no significant effect on bradykinin-induced contractions. 6. The B2 receptor antagonists Hoe 140 (10(-8) to 10(-6) M) and D-Arg [Hyp3, D-Phe7]-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 B2 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.