Effect of doxazosin with and without rho-kinase inhibitor on human corpus cavernosum smooth muscle in the presence of bladder outlet obstruction.
OBJECTIVE
We investigated the relationship of adrenergic responses in corpus cavernosum tissues in the presence of BOO using the alpha1-adrenergic receptor antagonist doxazosin (Pfizer, New York, New York) and the rho-kinase inhibitor Y-27632 (Calbiochem, San Diego, California).


METHODS
CCSM tissue was obtained from patients who underwent penile prosthesis implantation. Patients were divided into 2 groups according to the presence of BOO. The submaximal (EC80) concentration of phenylephrine (Sigma Chemical Co., St. Louis, Missouri) was calculated by evaluating adrenergic activity responses with cumulatively applied phenylephrine. After achieving a stable contraction plateau test compounds were put in an organ bath. The relaxant potencies of doxazosin and Y-27632 were expressed as the percent of inhibition of the contraction plateau induced EC80 concentration of phenylephrine. Relaxation responses in the 2 groups were compared.


RESULTS
At the highest dose of increasing concentrations phenylephrine generated 70% more contraction response in the BOO positive group than in the BOO negative group. Doxazosin and Y-27632 caused concentration dependent relaxation in CCSM precontracted by phenylephrine. With doxazosin significantly higher relaxation responses were attained in the BOO positive group in terms of log IC50 and the maximal relaxation response (p = 0.0353 and 0.0003, respectively). Maximum relaxation responses following Y-27632 administration were significantly higher in the BOO positive group.


CONCLUSIONS
The contractility of human corpus cavernosum is increased in the presence of BOO. Doxazosin and Y-27632 generate effective CCSM relaxation in the presence of BOO. Doxazosin and Y-27632 may be the alternatives for the treatment of erectile dysfunction associated with BPH.
Demir
Omer
O
Department of Urology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
Murat
Nergis
N
Aslan
Guven
G
Gidener
Sedef
S
Esen
Ahmet Adil
AA
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000368:Aged; D000577:Amides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017292:Doxazosin / Q000494:pharmacology*; D007172:Erectile Dysfunction / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects*; D010413:Penis / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D001748:Urinary Bladder Neck Obstruction / Q000150:complications / Q000503:physiopathology*; D054460:rho-Associated Kinases
D000317:Adrenergic alpha-Antagonists; 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; D017292:Doxazosin