title: Testosterone and atrial natriuretic peptide share the same pathway to induce vasorelaxation of human umbilical artery.
abstract: We recently observed in human umbilical artery smooth muscle cells that testosterone activates protein kinase G and stimulates large-conductance Ca²⁺ activated (BKCa) and voltage sensitive (KV) potassium channels. In the same work, we also show that atrial natriuretic peptide (ANP), an activator of particulate guanylate cyclase (pGC), stimulates the activity of BKCa and KV channels because of protein kinase G activation. The aim of this work was to prove that the relaxant effects of testosterone are also because of the increase of cGMP because of activation of the pGC. Subsarcolemmal cGMP signals were monitored in single cells by recording the cGMP-gated current (ICNG) in human umbilical artery smooth muscle cells expressing the wild-type rat olfactory cyclic nucleotide-gated (CNG) channel. Sodium nitroprusside (10 and 100 μM), ANP (0.1 and 1 μM), or testosterone (0.1, 1, and 10 μM) induced activation of ICNG. This activation induced by testosterone and ANP is bigger than that elicited by sodium nitroprusside. In summary, our study reveals that testosterone and ANP activate the pGC and induce vasorelaxation of human umbilical artery.
authors.affiliation: CICS-UBI, Centro de Investigação em Ciências da Saúde, University of Beira Interior, Covilhã, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Feiteiro
authors.forename: António J
authors.initials: AJ
authors.lastname: Santos-Silva
authors.forename: Ignacio
authors.initials: I
authors.lastname: Verde
authors.forename: Elisa
authors.initials: E
authors.lastname: Cairrão
mesh_terms: D000328:Adult; D009320:Atrial Natriuretic Factor / Q000494:pharmacology* / Q000502:physiology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000187:drug effects / Q000235:genetics; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009599:Nitroprusside / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects*; D013739:Testosterone / Q000494:pharmacology* / Q000502:physiology; D014469:Umbilical Arteries / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C518241:CNGA2 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels; D014665:Vasodilator Agents; D009599:Nitroprusside; D013739:Testosterone; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP