Diabetic urethropathy compounds the effects of diabetic cystopathy.

Abstract

PURPOSE:

The effects of short-term and long-term diabetes mellitus on urethral function were investigated to determine the contribution of urethral dysfunction to diabetes mellitus voiding dysfunction.

MATERIALS AND METHODS:

Isovolumetric bladder pressure, urethral perfusion pressure and external urethral sphincter electromyography were measured in urethane anesthetized, female Sprague-Dawley rats (Charles River Laboratories, Wilmington, Massachusetts) 5 or 10 weeks after streptozotocin induced diabetes mellitus. Urethral responses to serial administration of the skeletal muscle blocker alpha-bungarotoxin, the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine and the alpha-adrenergic agonist L-phenylephrine were determined in diabetes mellitus and age matched controls.

RESULTS:

Peak bladder pressures and contraction amplitudes were significantly decreased in diabetes mellitus rats. Detrusor-sphincter dyssynergia occurred in approximately 30% of diabetes mellitus rats but never in controls. Alpha-Bungarotoxin caused a greater decrease in baseline urethral perfusion pressure in diabetes mellitus rats than in controls (approximately 40% vs approximately 15%). Bladder contraction associated urethral smooth muscle relaxation amplitudes were significantly less in diabetes mellitus rats than in controls. N(omega)-nitro-L-arginine significantly suppressed urethral relaxation in controls but not in diabetes mellitus rats. L-phenylephrine significantly increased baseline urethral perfusion pressure in diabetes mellitus rats but not in controls. The unassociated conditions of insensitivity to N-nitro-L-arginine and hypersensitivity to L-phenylephrine were more common in 10-week diabetes mellitus rats than in control rats.

CONCLUSIONS:

Diabetes mellitus induced urethropathy is characterized by external urethral sphincter dysfunction, decreased urethral smooth muscle relaxation and nitric oxide responsiveness, and increased urethral smooth muscle responsiveness to alpha(1)-adrenergic agonists. These changes increase outlet resistance and, thereby, decrease voiding efficiency. This exacerbates voiding dysfunction, creating a vicious cycle of progressive lower urinary tract damage and dysfunction. Early intervention targeting outlet resistance may be indicated.

• Authors: Zhongguang Yang, Paul C Dolber, Matthew O Fraser
• Journal: The Journal of urology (J Urol) Vol. 178 Issue 5 Pg. 2213-9 (Nov 2007) ISSN: 0022-5347 [Print] United States
• PMID: 17870107 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Adrenergic alpha-Agonists
• Antibiotics, Antineoplastic
• Bungarotoxins
• Phenylephrine
• N(omega)-hydroxyarginine
• Streptozocin
• Arginine

Topics

• Adrenergic alpha-Agonists (administration & dosage)
• Animals
• Antibiotics, Antineoplastic (toxicity)
• Arginine (administration & dosage, analogs & derivatives)
• Bungarotoxins (administration & dosage)
• Diabetes Mellitus, Experimental (complications, physiopathology)
• Electromyography
• Female
• Follow-Up Studies
• Muscle Contraction (physiology)
• Phenylephrine (administration & dosage)
• Rats
• Rats, Sprague-Dawley
• Streptozocin (toxicity)
• Urethra (physiopathology)
• Urethral Diseases (drug therapy, etiology, physiopathology)
• Urinary Bladder (physiopathology)
• Urinary Bladder Diseases (drug therapy, etiology, physiopathology)