Mediation of bradykinin-induced contraction in canine veins via thromboxane/prostaglandin endoperoxide receptor activation.
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 greater than U44069 greater than BK greater than PGF2 alpha greater than TXB2 much greater than PGD2. 3. 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). 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.
Aksoy
M O
MO
Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140.
Harakal
C
C
Smith
J B
JB
Stewart
G J
GJ
Zerweck
C R
CR
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D005231:Fatty Acids, Unsaturated; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011449:Prostaglandin Endoperoxides / Q000378:metabolism*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000378:metabolism; D044262:Prostaglandin H2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011463:Prostaglandins H / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000378:metabolism*; D014680:Veins / Q000187:drug effects
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D007093:Imidazoles; D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D011725:Pyridines; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; D013931:Thromboxanes; C029166:dazoxiben; D044262:Prostaglandin H2; C040624:sulotroban; C049113:3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid; C045749:SQ 29548; D011451:Prostaglandin-Endoperoxide Synthases; D013930:Thromboxane-A Synthase; D001920:Bradykinin