PKG is involved in testosterone-induced vasorelaxation of human umbilical artery

The cyclic nucleotides involvement in the vasorelaxation induced by testosterone in human umbilical artery was investigated. The effect of this hormone on denuded human umbilical arteries contracted by serotonin (5-HT), histamine or KCl was analysed. Testosterone effect on potassium current (I-K) was also studied in human umbilical artery vascular smooth muscle cells (HUASMC). In general, the relaxant effects of testosterone, sodium nitroprusside (SNP) and atrial natriuretic peptide (ANP) are similar. The testosterone relaxant effect is not different to the induced by the conjoint application of ANP and testosterone. However, the effects of SNP and testosterone seem additive. The inhibition of protein kinase A (PKA) did not modify the testosterone relaxant effect, but protein kinase G (PKG) inhibition significantly reduced the testosterone effect independently of the contractile stimuli. In HUASMC, the I-K is mainly constituted by potassium exit through voltage sensitive (K-v) and large-conductance Ca2+ activated (BKCa) potassium channels. Testosterone significantly activates the basal I-K. SNP does not induce a significant modification in basal or testosterone stimulated I-K. In contrast, ANP stimulates the basal I-K, but does not increase the testosterone stimulation on I-K. The I-K increases induced by testosterone or by ANP are not significantly affected by the PKA inhibition, but are completely inhibited by the PKG inhibition. Our results show that testosterone and ANP stimulate the activity of BKCa, and K-v channels due to PKG activation and suggest that this hormone relaxes by activating particulate guanylate cyclase which increases the cGMP intracellular level. (C) 2010 Elsevier B.V. All rights reserved.