Alfuzosin attenuates erectile dysfunction in rats with partial bladder outlet obstruction

Serap Gur, Suresh C. Sikka, Surabhi Chandra, Padma Sandeep Koka, Krishna C. Agrawal, Philip J. Kadowitz, Wayne J.G. Hellstrom

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

OBJECTIVE: To determine how partial bladder outlet obstruction (PBOO) in a rat model affects erectile function, and whether an uroselective α1-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 α-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 α-adrenoceptor antagonists and phosphodiesterase-5 inhibitors in patients with ED and lower urinary tract symptoms.

Original languageEnglish (US)
Pages (from-to)1651-1657
Number of pages7
JournalBJU International
Volume102
Issue number11
DOIs
StatePublished - Dec 1 2008

Fingerprint

Urinary Bladder Neck Obstruction
Erectile Dysfunction
Smooth Muscle
Penis
Nitric Oxide Synthase
Adrenergic Receptors
alfuzosin
Phosphodiesterase 5 Inhibitors
Pressure
Nitric Oxide Synthase Type I
Lower Urinary Tract Symptoms
Paris
Nitroprusside
Phenylephrine
Nitric Oxide Synthase Type II
Urethra
Baths
Electric Stimulation
Biological Availability
Acetylcholine

Keywords

  • Alfuzosin
  • Erectile function
  • Nitric oxide synthase
  • Partial bladder outlet obstruction
  • Rat model

ASJC Scopus subject areas

  • Urology

Cite this

Gur, S., Sikka, S. C., Chandra, S., Koka, P. S., Agrawal, K. C., Kadowitz, P. J., & Hellstrom, W. J. G. (2008). Alfuzosin attenuates erectile dysfunction in rats with partial bladder outlet obstruction. BJU International, 102(11), 1651-1657. https://doi.org/10.1111/j.1464-410X.2008.07914.x

Alfuzosin attenuates erectile dysfunction in rats with partial bladder outlet obstruction. / Gur, Serap; Sikka, Suresh C.; Chandra, Surabhi; Koka, Padma Sandeep; Agrawal, Krishna C.; Kadowitz, Philip J.; Hellstrom, Wayne J.G.

In: BJU International, Vol. 102, No. 11, 01.12.2008, p. 1651-1657.

Research output: Contribution to journalArticle

Gur, S, Sikka, SC, Chandra, S, Koka, PS, Agrawal, KC, Kadowitz, PJ & Hellstrom, WJG 2008, 'Alfuzosin attenuates erectile dysfunction in rats with partial bladder outlet obstruction', BJU International, vol. 102, no. 11, pp. 1651-1657. https://doi.org/10.1111/j.1464-410X.2008.07914.x
Gur, Serap ; Sikka, Suresh C. ; Chandra, Surabhi ; Koka, Padma Sandeep ; Agrawal, Krishna C. ; Kadowitz, Philip J. ; Hellstrom, Wayne J.G. / Alfuzosin attenuates erectile dysfunction in rats with partial bladder outlet obstruction. In: BJU International. 2008 ; Vol. 102, No. 11. pp. 1651-1657.
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AU - Kadowitz, Philip J.

AU - Hellstrom, Wayne J.G.

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N2 - OBJECTIVE: To determine how partial bladder outlet obstruction (PBOO) in a rat model affects erectile function, and whether an uroselective α1-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 α-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 α-adrenoceptor antagonists and phosphodiesterase-5 inhibitors in patients with ED and lower urinary tract symptoms.

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