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

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Abstract
1 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. 2 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 > PGF2α > TXB2 > PGD2. 3 The cyclo-oxygenase inhibitors indomethacin (3 × 10−7 m) and flufenamic acid (10−5 m) reduced BK contractions without affecting those induced by noradrenaline (NA). 4 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. 5 The thromboxane synthase inhibitors dazoxiben (10−4 m) and CGS 12970 (10−5 m) had no significant inhibitory effect on BK-induced tension. 6 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.