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 (IK) 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 IK is mainly constituted by potassium exit through voltage sensitive (KV) and large-conductance Ca2+ activated (BKCa) potassium channels. Testosterone significantly activates the basal IK. SNP does not induce a significant modification in basal or testosterone stimulated IK. In contrast, ANP stimulates the basal IK, but does not increase the testosterone stimulation on IK. The IK 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 KV channels due to PKG activation and suggest that this hormone relaxes by activating particulate guanylate cyclase which increases the cGMP intracellular level.
Cairrão
Elisa
E
CICS-Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, and Centro Hospitalar da Cova da Beira E.P.E. Quinta do Alvito, 6200-251 Covilhã, Portugal.
Santos-Silva
António José
AJ
Verde
Ignacio
I
D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D004553:Electric Conductivity; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D011247:Pregnancy; D013739:Testosterone / Q000494:pharmacology*; D014469:Umbilical Arteries / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D015221:Potassium Channels; D013739:Testosterone; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D006152:Cyclic GMP