Orchidectomy modulates alpha2-adrenoceptor reactivity in rat mesenteric artery through increased thromboxane A2...

The present study evaluates the effect of endogenous male sex hormones on the reactivity to alpha2-adrenoceptor activation, and to analyze the role of the endothelium in this response in intact and endothelially denuded superior mesenteric arteries from control and orchidectomized male Sprague-Dawley rats. The concentration-dependent constriction induced by clonidine was analyzed in the absence and presence of the nitric oxide synthase (NOS) inhibitor, Nomega-nitro-L-arginine (L-NAME), cyclooxygenase (COX-1 and COX-2) inhibitors, indomethacin, the specific COX-2 inhibitor NS-398, the thromboxane-prostanoid receptor antagonist SQ29,548 and the thromboxane A2 (TXA2) synthase inhibitor, furegrelate. Endothelial NOS (eNOS), COX-2 and TXA2 synthase protein expression was studied by Western blot analysis. In addition, the basal and clonidine-stimulated production of TXB2, the stable TXA2 metabolite, was also measured. In intact vessels from control male rats, the concentration-dependent constriction induced by clonidine was increased by both L-NAME or endothelial removal, unaltered by indomethacin and decreased by NS-398; in denuded vessels, the clonidine response was decreased by NS-398 and unaltered by L-NAME, indomethacin, SQ29,548 or furegrelate. In intact vessels from orchidectomized rats, the constriction induced by clonidine was increased by L-NAME but practically abolished by indomethacin or NS-398; in endothelially denuded segments the clonidine response was unaltered by L-NAME, but was decreased by indomethacin, NS-398, SQ29,548 or furegrelate. Orchidectomy failed to modify eNOS,COX-2 and TXA2 synthase expression, and increased basal and clonidine-stimulated TXB2 release. These results show that TXA2 produced in smooth muscle cells is increased in mesenteric arteries from orchidectomized rats compared to their controls, and that this prostanoid is functionally involved in the vasoconstrictor response to clonidine only in arteries from the orchidectomized rats.