title: Understanding and targeting the Rho kinase pathway in erectile dysfunction.
abstract: Erectile dysfunction (ED) is a common disorder that affects a quarter of US men, and has many causes, including endothelial impairment, low testosterone levels, prior surgical manipulation, and/or psychogenic components. Penile erection is a complex process requiring neurally mediated relaxation of arteriolar smooth muscle and engorgement of cavernosal tissues, mediated by nitric oxide (NO). Current medical therapies for ED largely seek to maximize endogenous NO signalling. Certain aetiologies, including diabetes, are difficult to treat with current modalities, emphasizing the need for new molecular targets. Research has demonstrated the importance of RhoA-Rho-associated protein kinase (ROCK) signalling in maintaining a flaccid penile state, and inhibition of RhoA-ROCK signalling potentiates smooth-muscle relaxation in an NO-independent manner. The mechanisms and effects of RhoA-ROCK signalling and inhibition suggest that the RhoA-ROCK pathway could prove to be a new therapeutic target for the treatment of ED.
authors.affiliation: James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, 1800 Orleans Street/Marburg 134, Baltimore, MD 21287, USA.
authors.forename: Nikolai A
authors.initials: NA
authors.lastname: Sopko
authors.affiliation: James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, 1800 Orleans Street/Marburg 134, Baltimore, MD 21287, USA.
authors.forename: Johanna L
authors.initials: JL
authors.lastname: Hannan
authors.affiliation: James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, 1800 Orleans Street/Marburg 134, Baltimore, MD 21287, USA.
authors.forename: Trinity J
authors.initials: TJ
authors.lastname: Bivalacqua
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D003920:Diabetes Mellitus / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D006973:Hypertension / Q000201:enzymology; D008297:Male; D058990:Molecular Targeted Therapy; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D010413:Penis / Q000187:drug effects; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D054460:rho-Associated Kinases