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Am J Physiol Regul Integr Comp Physiol 293: R793-R803, 2007. First published May 23, 2007; doi:10.1152/ajpregu.00034.2007
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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Aging impairs neurogenic contraction in guinea pig urinary bladder: role of oxidative stress and melatonin

Pedro J. Gómez-Pinilla, Maria J. Pozo, and Pedro J. Camello

Department of Physiology, Faculty of Veterinary Sciences, University of Extremadura, Cáceres, Spain

Submitted 18 January 2007 ; accepted in final form 21 May 2007

The incidence of urinary bladder disturbances increases with age, and free radical accumulation has been proposed as a causal factor. Here we investigated the association between changes in bladder neuromuscular function and oxidative stress in aging and the possible benefits of melatonin treatment. Neuromuscular function was assessed by electrical field stimulation (EFS) of isolated guinea pig detrusor strips from adult and aged female guinea pigs. A group of adult and aged animals were treated with 2.5 mg·kg–1·day–1 melatonin for 28 days. Neurotransmitter blockers were used to dissect pharmacologically the EFS-elicited contractile response. EFS induced a neurogenic and frequency-dependent contraction that was impaired by aging. This impairment is in part related to a decrease in detrusor myogenic contractility. Age also decreased the sensitivity of the contraction to pharmacological blockade of purinergic and sensitive fibers but increased the effect of blockade of nitrergic and adrenergic nerves. The density of cholinergic and nitrergic nerves remained unaltered, but aging modified afferent fibers. These changes were associated with an increased level of markers for oxidative stress. Melatonin treatment normalized oxidative levels and counteracted the aging-associated changes in bladder neuromuscular function. In conclusion, these results show that aging modifies neurogenic contraction and the functional profile of the urinary bladder plexus and simultaneously increases the oxidative damage to the organ. Melatonin reduces oxidative stress and improves the age-induced changes in bladder neuromuscular function, which could be of importance in reducing the impact of age-related bladder disorders.

detrusor smooth muscle; neuromuscular function; sensory nerves; electrical field stimulation


Address for reprint requests and other correspondence: P. J. Camello, Faculty of Veterinary Sciences, Dept of Physiology, Campus Universitario s/n, 10071 Cáceres, Spain (e-mail: pcamello{at}unex.es)






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