Effects of partial outlet obstruction on bladder-strip sensitivity to glucose deprivation: an in vitro study in the rat

Abstract

Partial outlet obstruction has been shown to result in contractile and metabolic dysfunctions. Specifically, there is a greater reduction in the response to field stimulation (FS) in comparison with the responses to bethanechol and KC1, a greater reduction in the tonic response to stimulation in comparison with the phasic response, and a reduction in oxidative metabolism of glucose accompanied by an increase in the glycolytic metabolism of glucose. The specific aim of the current study was to correlate the effects of partial outlet obstruction on the contractile responses of isolated strips of bladder smooth muscle to repetitive stimulation in the presence and absence of glucose. Adult male Sprague-Dawley rats were subjected to partial outlet obstruction by the surgical placement of silk ligatures around the urethra. After 2 weeks, each rate was anesthetized, the bladder was excised, and isolated strip studies were performed. These studies demonstrated that the maximal phasic response to FS was significantly decreased in the obstructed strips as compared with controls, with no difference being noted for responses to bethanechol or KC1; the tonic responses to all forms of stimulation were significantly decreased after obstruction, with the tonic response to FS being decreased to a greater degree than were the tonic responses to bethanechol and KC1; and in the absence of glucose, the tonic responses of control strips to all forms of stimulation were reduced to a greater degree than were the phasic responses. These studies demonstrate that the tonic response to FS is extremely sensitive to fatigue induced by repetitive stimulation.Bladder dysfunction secondary to benign prostatic hypertrophy (BPH) are characterized by urgency, frequency, weak urine stream, and an increase in residual volume [3]. These symptoms of BPH are believed to be related to alterations in the contractile function of the hypertrophied Correspondence to: R. M. Levin, Division of Urology, 3010 Ravdin Courtyard Building, Hospital detrusor. However, the etiology of these symptoms is not well understood [3].Animal models of partial outlet obstruction have been utilized to stimulate bladder hypertrophy secondary to BPH and reproduce the clinical urodynamic picture [12,13]. There are several characteristics of the effects of experimental partial outlet obstruction that may directly relate to the urodynamic dysfunctions observed in BPH patients. They include a denervation and reduction in the response to neuronal stimulation (see current reviews [12,13]). In isolated bladder preparations, this is reflected by a greater reduction in the contractile response (release of neurotransmitters from nerve terminals) to field stimulation (FS) in comparison with the response to bethanechol (direct muscarinic activation) or KC1 (direct depolarization of the smooth muscle ) [1,7,9]. In addition, it has been suggested that partial outlet obstruction increases the sensitivity of the bladder to repetitive stimulation (an increase in the rate of fatigue) [14]. In relat...