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Am J Physiol Regul Integr Comp Physiol (May 23, 2007). doi:10.1152/ajpregu.00034.2007
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Submitted on January 18, 2007
Accepted on May 21, 2007

AGING IMPAIRS NEUROGENIC CONTRACTION IN GUINEA PIG URINARY BLADDER. THE ROLE OF OXIDATIVE STRESS AND MELATONIN

Pedro Julian Gomez-Pinilla1, Maria J. Pozo1, and Pedro Javier Camello1*

1 Dept. of Physiology, University of Extremadura, Caceres, Caceres, Spain

* To whom correspondence should be addressed. E-mail: pcamello{at}unex.es.

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 on 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 mgkg-1day-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 which was impaired by aging. This impairment is in part related to a decrease in the 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 ageing modified afferent fibers. These changes were associated to an increased level of markers for oxidative stress. Melatonin treatment normalized oxidative levels and counteracted the ageing-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 to reduce the impact of age-related bladder disorders.







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