Alfuzosin attenuates erectile dysfunction in rats with partial bladder outlet obstruction.

Abstract

OBJECTIVE:

To determine how partial bladder outlet obstruction (PBOO) in a rat model affects erectile function, and whether an uroselective alpha1-adrenoceptor antagonist, alfuzosin (Sanofi-Aventis, Paris, France) attenuates any erectile dysfunction (ED).

MATERIALS AND METHODS:

Adult male Sprague-Dawley rats (120) were randomized into four groups: 1, sham-operated; 2, alfuzosin-treated; 3, PBOO; and 4, alfuzosin-treated with PBOO. Groups 3 and 4 were subjected to PBOO for 6 weeks by ligation of the urethra, while groups 2 and 4 rats received daily oral alfuzosin (10 mg/day) for 6 weeks. In vivo erectile responses were monitored by evaluating ratios of intracavernosal pressure (ICP)/mean arterial pressure, and total ICP (area under the curve). Organ-bath studies were performed on corpus cavernosum smooth muscle (CCSM) strips. Nitric oxide synthase (NOS) expression was determined immunohistochemically (IHC) for neuronal (n)NOS and by Western blot analysis for endothelial (e) and inducible (i) NOS protein.

RESULTS:

Rats with PBOO showed lower erectile responses than controls. Maximum electrical field stimulation-mediated and endothelium-dependent acetylcholine-induced relaxations and contractile responses to phenylephrine were significantly reduced in CCSM strips from the PBOO group. The NO donor sodium nitroprusside completely relaxed CCSM from rats in all groups. IHC analyses showed decreased expression of nNOS in PBOO groups compared with controls; by contrast, protein expression of eNOS and iNOS was increased. Alfuzosin-treatment partially attenuated functional and molecular changes in penises of PBOO rats.

CONCLUSION:

Rats with PBOO show ED, most likely due to altered NOS expression and NO bioavailability. The alpha-adrenoreceptor antagonist alfuzosin reversed this ED by altering sympathetic tone, increasing NO-induced relaxation and augmenting blood flow in the penis. This study suggests a rationale for further clinical trials using combinations of alpha-adrenoceptor antagonists and phosphodiesterase-5 inhibitors in patients with ED and lower urinary tract symptoms.

• Authors: Serap Gur, Suresh C Sikka, Surabhi Chandra, Padma Sandeep Koka, Krishna C Agrawal, Philip J Kadowitz, Wayne J G Hellstrom
• Journal: BJU international (BJU Int) Vol. 102 Issue 11 Pg. 1651-7 (Dec 2008) ISSN: 1464-410X [Electronic] England
• PMID: 18990166 (Publication Type: Journal Article)

Chemical References

• Adrenergic alpha-Antagonists
• Quinazolines
• alfuzosin
• Nitric Oxide Synthase

Topics

• Adrenergic alpha-Antagonists (therapeutic use)
• Animals
• Blotting, Western
• Erectile Dysfunction (drug therapy, etiology, physiopathology)
• Immunohistochemistry
• Male
• Muscle Contraction (drug effects)
• Muscle Relaxation (drug effects)
• Nitric Oxide Synthase (metabolism)
• Penile Erection (drug effects)
• Penis (blood supply, drug effects, physiopathology)
• Quinazolines (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Urinary Bladder Neck Obstruction (complications, physiopathology)