Alfuzosin attenuates erectile dysfunction in rats with partial bladder outlet obstruction

Area of Science:

• Urology
• Pharmacology
• Physiology

Background:

• Partial bladder outlet obstruction (PBOO) is a common condition that can lead to lower urinary tract symptoms.
• Erectile dysfunction (ED) is a frequent comorbidity associated with PBOO.
• The underlying mechanisms linking PBOO to ED are not fully understood but may involve altered nitric oxide (NO) signaling.

Purpose of the Study:

• To investigate the impact of PBOO on erectile function in a rat model.
• To evaluate the efficacy of alfuzosin, an uroselective alpha1-adrenoceptor antagonist, in ameliorating PBOO-induced ED.
• To explore the effects of PBOO and alfuzosin on nitric oxide synthase (NOS) expression in penile tissues.

Main Methods:

• Adult male Sprague-Dawley rats underwent sham operation or PBOO for 6 weeks.
• Rats received daily oral administration of alfuzosin (10 mg/day) or vehicle.
• Erectile function was assessed in vivo by measuring intracavernosal pressure (ICP)/mean arterial pressure ratios.
• Corpus cavernosum smooth muscle (CCSM) strips were studied in organ baths for relaxation and contraction responses.
• Expression of neuronal (n)NOS, endothelial (e)NOS, and inducible (i)NOS was determined using immunohistochemistry and Western blot analysis.

Main Results:

• PBOO significantly impaired erectile responses compared to sham-operated controls.
• CCSM strips from PBOO rats exhibited reduced relaxation to electrical field stimulation and acetylcholine, but normal relaxation to sodium nitroprusside.
• Phenylephrine-induced contractions were diminished in CCSM from PBOO rats.
• nNOS expression decreased, while eNOS and iNOS expression increased in PBOO rat penises.
• Alfuzosin treatment partially attenuated the functional and molecular changes associated with PBOO-induced ED.

Conclusions:

• PBOO induces erectile dysfunction in rats, associated with altered NOS expression and reduced NO bioavailability.
• Alfuzosin demonstrated a partial reversal of ED, suggesting a role in modulating sympathetic tone and enhancing NO-mediated penile blood flow.
• These findings support further clinical investigation of alpha-adrenoceptor antagonists, potentially in combination with phosphodiesterase-5 inhibitors, for managing ED in patients with lower urinary tract symptoms.