Mediation of bradykinin-induced contraction in canine veins via thromboxane/prostaglandin endoperoxide receptor activation

Abstract

Canine jugular and femoral veins were studied to determine the possible importance of thromboxane (TXA2) and prostaglandin endoperoxides (prostaglandin H2, PGH2) in mediating bradykinin(BK)-induced contraction. Isolated vein rings incubated in modified Krebs solution contracted to TXA2/PGH2 analogs SQ26655 and U44069 with potency of contraction exceeding that for BK. The potency ranking for both veins was SQ26655 > U44069 > BK > PGF(2α) > TXB2 ≥ PGD2. The cyclo-oxygenase inhibitors indomethacin (3 x 10-7 M) and flufenamic acid (10-5 M) reduced BK contractions without affecting those induced by noradrenaline (NA). TXA2/PGH2 receptor antagonists SQ29548 (10-8 M) and BM13177 (10-6 M) strongly inhibited BK-induced tension. The action of antagonists was reversible with negligible influence on NA-elicited contraction. Selective removal of endothelium had no effect on BK-induced contraction or the action of the antagonists. The thromboxane synthase inhibitors dazoxiben (10-4 M) and CGS 12970 (10-5 M) had no significant inhibitory effect on BK-induced tension. These results suggest that in canine jugular and femoral vein, the action of BK is largely dependent upon stimulation of the cyclo-oxygenase pathway to produce PGH2 and possibly TXA2, which can activate a smooth muscle TXA2/PGH2 receptor to elicit vasoconstriction.