Chronic ischemia increases prostatic smooth muscle contraction in the rabbit.
OBJECTIVE
We studied the effect of chronic ischemia on prostatic smooth muscle contraction in the rabbit.


METHODS
New Zealand male rabbits weighing 3 to 3.5 kg were assigned to 2 groups. Group 1 (10 rabbits) underwent balloon endothelial injury of the iliac arteries and received a 0.5% cholesterol diet for 4 weeks and then a regular diet for 8 weeks. Control group 2 (10 rabbits) received a regular diet. After 12 weeks the animals were anesthetized. Iliac artery and prostate blood flow was recorded. Prostate tissues were prepared for isometric tension measurement, enzyme immunoassay to determine cyclic guanosine monophosphate (cGMP) release and histological examination.


RESULTS
In group 1 atherosclerosis as well as a significant decrease in iliac artery and prostate blood flow were observed. Ischemia significantly increased prostatic tissue contraction, decreased cGMP release and led to capsular and stromal thickening, and epithelial atrophy. The alpha1-adrenoceptor blocker doxazosin and the phosphodiesterase-5 inhibitor sildenafil citrate significantly decreased the contraction of control and ischemic tissues. Doxazosin was more effective in decreasing contractions when it was combined with sildenafil or the nitric oxide (NO) precursor L-arginine. In contrast, doxazosin was less effective when it was combined with the NO synthase inhibitor N omega-nitro-L-arginine or with the guanylate cyclase inhibitor methylene blue. Doxazosin significantly increased cGMP release in control tissues but not in ischemic tissues. Sildenafil significantly increased cGMP release in control and ischemic tissues.


CONCLUSIONS
Ischemia increased prostatic smooth muscle contraction and led to marked structural damage. Stimulators of NO synthesis and cGMP production enhanced the efficacy of doxazosin in decreasing prostatic tissue contraction. Sildenafil decreased contractility and increased cGMP release. Increased smooth muscle tone and structural changes in the ischemic prostate may suggest a role for prostate ischemia in resistance to urinary flow independent of prostate size.
Azadzoi
Kazem M
KM
Department of Urology, Boston University School of Medicine, Massachusetts 02130, USA.
Babayan
Richard K
RK
Kozlowski
Robert
R
Siroky
Mike B
MB
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001161:Arteriosclerosis / Q000503:physiopathology; D001783:Blood Flow Velocity; D006152:Cyclic GMP / Q000378:metabolism; D017292:Doxazosin / Q000494:pharmacology; D004558:Electric Stimulation; D007083:Iliac Artery; D066298:In Vitro Techniques; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011467:Prostate / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D011687:Purines; D011817:Rabbits; D000068677:Sildenafil Citrate; D013450:Sulfones
D000317:Adrenergic alpha-Antagonists; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009569:Nitric Oxide; D001120:Arginine; D000068677:Sildenafil Citrate; D006152:Cyclic GMP; D017292:Doxazosin