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Tep-areenan P, Kendall DA, Randall MD: Testosterone-induced vasorelaxation in the rat mesenteric arterial bed is mediated predominantly via potassium channels. Br J Pharmacol. 2002 Feb;135(3):735-40.
We have investigated the involvement of nitric oxide and K (+) channels in the vasorelaxant responses to physiologically-relevant concentrations of testosterone in the rat isolated mesenteric arterial bed. Testosterone (100 pM - 10 microM) elicited concentration-dependent relaxations in the isolated mesenteric arterial bed (pEC (50)=9.47 (9.22 - 9.73, 95% CI), maximal relaxation, R (max)=62.8+/-2.0%, n=6). A nitric oxide synthase (NOS) inhibitor, N (G)-nitro-L-arginine methyl ester (L-NAME, 300 microM) or removal of the endothelium significantly inhibited maximal relaxations to testosterone (L-NAME: R (max)=51.4+/-1.1%, P <0.01, n=6; endothelium-denuded: R (max)=46.9+/-2.8%, P <0.001, n=5). Raising the extracellular K (+) concentration to 30 and 60 mM, or pre-treatment with 300 microM tetrabutylammonium chloride (TBA), a calcium-activated K (+) channel inhibitor, abolished vasorelaxations induced by testosterone. A selective inhibitor of ATP-sensitive K (+) (K (ATP)) channels, glibenclamide (10 microM) and an inhibitor of voltage-sensitive K (+) (K (V)) channels, 4-aminopyridine (4-AP, 1 mM) did not affect testosterone-induced responses. Vasorelaxation to 1 microM testosterone was significantly (P <0.05) inhibited by 100 nM charybdotoxin (ChTx), an inhibitor of large conductance calcium-activated K (+) (BK (Ca)) channels (control: 63.3+/-9.9%, n=6; ChTx: 11.9+/-12.7%, n=3). Neither the testosterone receptor antagonist, flutamide (10 microM) nor an aromatase inhibitor, aminoglutethimide (10 microM) inhibited testosterone-induced responses. In conclusion, the present findings demonstrate, in the rat isolated mesenteric arterial bed, that testosterone causes acute vasorelaxations at physiologically relevant concentrations which are, in part, mediated via NO- and endothelium-dependent pathways. However, the activation of BK (Ca) channels plays a substantial role in testosterone-induced vasorelaxation. |
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