Nitric oxide inhibits RhoA/Rho-kinase signaling to cause penile erection.
The RhoA/Rho-kinase pathway mediates vasoconstriction in the cavernosal circulation. Inhibition of this pathway leads to penile erection in the in vivo rat model. These studies examined the hypothesis that nitric oxide (NO) inhibits RhoA/Rho-kinase signaling as part of normal erection. The results show that NO causes increased intracavernosal pressure and that this response is potentiated by prior treatment with a threshold dose of the Rho-kinase inhibitor, (+)-(R)-trans-4-(1-Aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride, monohydrate (Y-27632). These results support the hypothesis that NO inhibits Rho-kinase-induced cavernosal vasoconstriction during erection.
Mills
Thomas M
TM
Department of Physiology, Medical College of Georgia, Augusta, GA, USA. tmills@mail.mcg.edu
Chitaley
Kanchan
K
Lewis
Ronald W
RW
Webb
R Clinton
RC
D000577:Amides / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009574:Nitro Compounds / Q000494:pharmacology; D010410:Penile Erection / Q000187:drug effects / Q000502:physiology*; D010413:Penis / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014661:Vasoconstriction / Q000187:drug effects; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000502:physiology*
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D020030:Nitric Oxide Donors; D009574:Nitro Compounds; D011725:Pyridines; C101316:methyl-2-hydroxyimino-5-nitro-6-methoxy-3-hexeneamide; C108830:Y 27632; D009569:Nitric Oxide; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein