U-46619-induced potentiation of noradrenergic constriction in the human saphenous vein: antagonism by thromboxane receptor blockade

Abstract

Objective: We investigated the potentiating effect of U-46619, a synthetic analogue of thromboxane A₂ (TXA₂), on the adrenergic responses in human saphenous vein. Methods: Saphenous vein rings were obtained from 35 patients undergoing coronary artery bypass surgery. The rings were suspended in organ bath chambers for isometric recording of tension. Results: U-46619 (10⁻¹⁰–3×10⁻⁷ mol/l) produced concentration-dependent and endothelium-independent contractile responses. U-46619 (10⁻¹⁰ mol/l) potentiated the contractions elicited by electrical stimulation and potassium chloride, and produced leftward shifts of the concentration–response curve for noradrenaline. The TXA₂ receptor antagonist SQ-30741 (10⁻⁸ mol/l) prevented the potentiation evoked by U-46619. The dihydropyridine calcium antagonist nifedipine (10⁻⁶ mol/l) did not affect the potentiation of electrical stimulation and noradrenaline induced by U-46619, but abolished the potentiation of U-46619 on KCl-induced contractions. Conclusions: U-46619 facilitates sympathetic neurotransmission and potentiates constrictor effects of noradrenaline in human saphenous veins through stimulation of TXA₂ receptors. These effects are independent of calcium entry through dihydropyridine calcium channels.

Adrenergic (ant)agonists, Ca-channel, Receptors, Vasoconstriction/dilation, Veins, Endothelial factors, Vasoactive agents