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 > PGF2α > TXB2 > PGD2. 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). 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.

Pharmacological Analysis of the Rat Femoral Artery Response to Bradykinin

“…A number of studies demonstrated that the different cyclooxygenase products of arachidonic acid, such as prostaglandin F 2α (PGF 2α ), prostaglandin H 2 (PGH 2 ), or thromboxane A 2 (TXA 2 ), have been involved in the bradykinin contractile effects in various blood vessels [12, 23–27]. Our results were in line with the quoted studies, since cyclooxygenase inhibition completely abolished the bradykinin-produced contraction of the femoral artery.…”

Different Prostanoids Are Involved in Bradykinin-Induced Endothelium-Dependent and -Independent Vasoconstriction in Rat Mesenteric Resistance Arteries

“…The bradykinin-induced vasoconstrictor response has been reported to be endothelium-independent and indomethacin-sensitive or mediated by bradykinin B 2 receptors located in the vascular smooth-muscle layer (2,9). In addition, other studies have shown that the action of bradykinin was largely dependent on stimulation of the cyclooxygenase pathway to produce PGH 2 and possibly TXA 2 , which can activate smooth muscle TXA 2 / PGH 2 receptors to elicit vasoconstriction (10,11). However, the bradykinin-induced vasoconstriction in the canine isolated saphenous vein without endothelium was potentiated by indomethacin (26).…”

“…Thus, this finding strongly suggests that PGH 2 is responsible for the bradykinin-induced endotheliumindependent vasoconstriction in the rat mesenteric artery. Bradykinin has been shown to cause vasoconstriction (10,24,25). The bradykinin-induced vasoconstrictor response has been reported to be endothelium-independent and indomethacin-sensitive or mediated by bradykinin B 2 receptors located in the vascular smooth-muscle layer (2,9).…”

Vázizomkisvénák vazomotortónusának intrinszik szabályozómechanizmusai

“…A különböző AA-metabolitok kisvénákban kifejtett vazoaktív hatásai régió-és fajfüggő különbsége-ket mutattak, például humán vena saphenában a prosztaciklin kontrakciót, míg kézvénákban relaxációt okozott [45]. Továbbá számos vazoaktív anyagról és mechanikai faktorról igazolták, hogy befolyásolják az érfalban tör-ténő prosztaglandinok termelését, ezáltal szabályozva a kisvénák vazomotortónusát [46,47]. Feltételezhető, hogy a különböző lokális humorális és biomechanikai té-nyezők egymás hatását is módosítva, együttesen határoz-zák meg a vascularis endothelialis faktorok termelését és ezáltal szabályozzák a kisvénák tónusát.…”