[Inhibition of tonic contraction of smooth muscle: a new approach to achieve erection dysfunction].
It has shown that vasoconstriction in the cavernosal circulation is mediated by the RhoA/Rho-kinase calcium sensitization pathway. Inhibition of Rho-kinase activity in cavernosal smooth muscle with Y-27632 resulted in an erectile response marked by elevated intracavernosal pressure (ICP) without a significant change in men arterial pressure (MAP). To explain how erection can occurred in the presence of this strong vasoconstrictive signal, we have hypothesized that nitric oxide (NO) induces vasodilation leading to erection by directly inhibiting activity of the RhoA/Rho-kinase pathway, thereby reducing vasoconstriction. Administration of Y-27632 restored erectile function in rat models of hypogonadism and hypertension, suggesting that Rho-kinase inhibition may have potential clinical value. In addition, our results show that topical application of Y-27632 may be an effective mode of treatment for erectile dysfunction.
Dai
Yu-Tian
YT
Department of Urology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210008, China.
Mills
Thomas M
TM
Lewis
Ronald W
RW
Webb
R Clinton
RC
D000577:Amides / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D010410:Penile Erection / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000577:Amides; D047908:Intracellular Signaling Peptides and Proteins; D009125:Muscle Relaxants, Central; D011725:Pyridines; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein