Differential vasoreactivity to the thromboxane A2 mimic U-46619 of collateral and normal peripheral blood vessels in situ perfused rat hindquarters.
In situ perfusion of rat hindquarters was performed through both iliac arteries. Perfusion pressures were measured concomitantly in the normal vascular bed and in the ligation-induced collateral bed of the left and right hindleg, respectively. An increased vaso-constrictive response of the collateral versus normal blood vessels was found after bolus injections of increasing concentrations of the thromboxane A2 (TXA2) mimic U-46619. This increased reactivity was related to a difference in vascular structure and in receptor-mediated sensitivity. The vasoconstrictive effect of U-46619 was dose-dependently inhibited by the combined TXA2 synthetase inhibitor-TXA2/prostaglandin endoperoxide (PGH2) receptor antagonist ridogrel and the single TXA2/PGH2 receptor antagonist sulotroban. Selective blockade of alpha 1-, alpha 2-, beta 1-beta 2- and S2-receptors, cyclooxygenase inhibition, TXA2 synthesis inhibition, amine depletion and amine uptake blockade had no influence on the vasoconstrictive action of U-46619. Ca2+ entry blockade by flunarizine and nifedipine significantly reduced the vasoconstriction. This study shows that (1) rat peripheral collaterals in relation to normal arterial blood vessels are significantly more reactive to TXA2; (2) the vasoconstrictive effect of U-46619 is mediated predominantly by TXA2/PGH2 receptors; (3) the activation of these receptors elicits indirectly transmembrane Ca2+ entry to trigger vasoconstriction.
Verheyen
A
A
Department of Haematology, Janssen Research Foundation, Beerse, Belgium.
Lauwers
F
F
Vlaminckx
E
E
De Clerck
F
F
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D007083:Iliac Artery / Q000502:physiology*; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000494:pharmacology; D051381:Rats; D013928:Thromboxane A2 / Q000494:pharmacology*
D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D044262:Prostaglandin H2; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid