Elevated RhoA/Rho-kinase activity in the aged rat penis: mechanism for age-associated erectile dysfunction

Epidemiologic studies have shown that aging accounts significantly for the prevalence of erectile dysfunction (ED). The pathophysiology of ED during aging and its underlying molecular mechanisms are largely unknown. We hypothesized that increased RhoA/Rho‐kinase signaling is a major factor in the pa...

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Bibliographic Details
Published in:The FASEB journal 2006-03, Vol.20 (3), p.536-538
Main Authors: Jin, Liming, Liu, Tongyun, Lagoda, Gwen A, Champion, Hunter C, Bivalacqua, Trinity J, Burnett, Arthur L
Format: Article
Language:English
Subjects:
Aging - physiology
Amides - pharmacology
Amides - therapeutic use
Amino Acid Substitution
Animals
corpus cavernosum
Dependovirus - genetics
Erectile Dysfunction - enzymology
Erectile Dysfunction - etiology
Erectile Dysfunction - physiopathology
Erectile Dysfunction - therapy
erection
Genetic Therapy
Genetic Vectors - genetics
Genetic Vectors - therapeutic use
Intracellular Signaling Peptides and Proteins
Isoenzymes - physiology
Male
Muscle Contraction - physiology
Muscle, Smooth, Vascular - physiopathology
Mutation, Missense
myosin light chain phosphatase
Myosin-Light-Chain Phosphatase - physiology
Penis - enzymology
Penis - physiopathology
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Protein-Serine-Threonine Kinases - physiology
Pyridines - pharmacology
Pyridines - therapeutic use
Rats
Rats, Inbred F344
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - physiology
rho-Associated Kinases
rhoA GTP-Binding Protein - genetics
rhoA GTP-Binding Protein - physiology
smooth muscle
Vasodilation - drug effects
Vasodilation - physiology
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Summary:Epidemiologic studies have shown that aging accounts significantly for the prevalence of erectile dysfunction (ED). The pathophysiology of ED during aging and its underlying molecular mechanisms are largely unknown. We hypothesized that increased RhoA/Rho‐kinase signaling is a major factor in the pathogenesis of age‐associated ED and the mechanism involves increased penile smooth muscle contractility through inhibition of myosin light chain phosphatase. Male Fischer 344 young (4 month old) and aged (20–22 month old) rats underwent erectile function testing in vivo by measuring intracavernosal pressure (ICP) and mean arterial blood pressure (MAP) upon electrical stimulation of the cavernous nerve. The data demonstrated that erectile function was significantly lower in aged rats than that in young rats at all voltages tested (P
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.05-4232fje