Research Findings on Overactive Bladder.

Several physiopathologic conditions lead to the manifestation of overactive bladder (OAB). These conditions include ageing, diabetes mellitus, bladder outlet obstruction, spinal cord injury, stroke and brain injury, Parkinson's disease, multiple sclerosis, interstitial cystitis, stress and depression. This review has discussed research findings in human and animal studies conducted on the above conditions. Several structural and functional changes under these conditions have not only been observed in the lower urinary tract, but also in the brain and spinal cord. Significant changes were observed in the following areas: neurotransmitters, prostaglandins, nerve growth factor, Rho-kinase, interstitial cells of Cajal, and ion and transient receptor potential channels. Interestingly, alterations in these areas showed great variation in each of the conditions of the OAB, suggesting that the pathophysiology of the OAB might be different in each condition of the disease. It is anticipated that this review will be helpful for further research on new and specific drug development against OAB.

Estrous cycle alters micturition pattern in conscious rat.

BACKGROUND: The present study aims to investigate the influence of estrous cycle on micturition pattern in conscious spontaneously hypertensive rat. METHODS: Micturition pattern was evaluated by measuring void volume, void interval and void pressure in each stage of the estrous cycle by cystometry. RESULTS: A higher bladder capacity and a decrease in the frequency of micturition occurred in the proestrus and estrus stage, while a lower bladder capacity and an increase in the frequency of micturition occurred in the diestrus stage. CONCLUSIONS: It is suggested that these remarkable variations in the physiology of the micturition pattern during different stages of the estrous cycle might be due to the effects of estrogen and progesterone because the level of these hormones fluctuate during each stage of the cycle. Therefore, monitoring the estrous cycle prior to any cystometry experiment in conscious rat is recommended for a better understanding of the effects of these hormones on bladder function.

Sex differences in the physiology and pharmacology of the lower urinary tract.

Sexual dimorphism is not only noticed in the prevalence of many diseases, but also in multiple physiological functions in the body. This review has summarized findings from published literature on the sex differences of the pathophysiology and pharmacology of the lower urinary tract (LUT) of humans and animals. Sex differences have been found in several key areas of the LUT, such as overactive bladder, expression and function of neurotransmitter receptors in the bladder and urethra, and micturition patterns in humans and animals. It is anticipated that this review will not only evoke renewed interest for further research on the mechanism of sex differences in the pathophysiology of the LUT (especially for overactive bladder), but might also open up the possibilities for gender-based drug development by pharmaceutical industries in order to find separate cures for men and women with diseases of the LUT.

Enhanced sensitivity to afferent stimulation and impact of overactive bladder therapies in the conscious, spontaneously hypertensive rat.

The spontaneously hypertensive rat (SHR) has been proposed as an overactive bladder model, driven, at least partially, by alterations in bladder innervation. To assess the functional role of sensory bladder afferents we evaluated the conscious cystometric response to prostaglandin E(2) (PGE(2)) or acetic acid (AA) bladder infusion. SHR demonstrated a hypersensitivity to PGE(2) and AA, as indicated by a greater reduction in both void volume (VV) and micturition interval (MI) compared with Sprague-Dawley controls. The heightened PGE(2) and AA responses in the SHR were inhibited by capsaicin desensitization, supporting a role for bladder afferents in facilitating the hypersensitivity. Furthermore, we characterized the SHR pharmacologically using overactive bladder therapeutic agents. In the SHR, both darifenacin and oxybutynin (M(3)-selective and nonselective muscarinic antagonists, respectively) reduced micturition pressure (MP) and functional bladder capacity (VV and MI). In sharp contrast, functional bladder capacity was significantly enhanced by ß(3)-adrenoceptor agonism [5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL316243)], and by gabapentin, without effect on MP. These data provide the first functional evidence for hypersensitive bladder afferents in the SHR and provide a pharmacological benchmark in this model for overactive bladder therapeutics. These data also support the idea that ß(3)-adrenoceptor agonism and gabapentin may provide a more effective overactive bladder therapy than muscarinic antagonism.

Effect of estrogen and progesterone on urodynamics in the conscious rat.

OBJECTIVES: To examine the effects of estrogen and/or progesterone on the cystometric profiles obtained using continuous-filling cystometry in the conscious Sprague-Dawley rat. METHODS: Sprague-Dawley rats underwent ovariectomy (OVX) and were compared with controls by conscious continuous-filling cystometry. The effect of estrogen (10 microg/kg/d for 14 days) and/or progesterone (10 mg/kg/d for 14 days) replacement on OVX urodynamics was examined (n = 7-8/group). RESULTS: OVX rats demonstrated reduced micturition intervals and voided volumes compared with controls. These effects of OVX were reversed by estrogen replacement, but not by progesterone replacement. When combined with estrogen, progesterone functioned to partially antagonize the effects of estrogen in OVX rats. CONCLUSIONS: Estrogen enhances bladder capacity in the OVX rat and therefore is a likely contributor to the larger bladder capacity in the female compared with the male rat. Consistent with its established role in reproductive physiology, progesterone antagonizes the beneficial effects of estrogen on OVX rat urodynamics.