Basic scienceTherapeutic Effects of Endothelin-A Receptor Antagonist on Bladder Overactivity in Rats with Chronic Spinal Cord Injury
Section snippets
Material and Methods
We used adult female Sprague-Dawley rats (250 to 350 g). All experiments were conducted in accordance with institutional guidelines and approved by the University of Pittsburgh Institutional Animal Care and Use Committee.
Cystometry
During awake cystometry, all spinalized rats showed NVCs before large amplitude voiding bladder contractions occurred (Fig. 1). The amplitude of NVCs increased as the bladder was filled with saline infusion. The mean amplitude and mean number of NVCs per voiding cycle were 17.3 ± 3.6 cmH2O and 4.1 ± 0.6, respectively (Table 1). ABT-627 (1 mg/kg, iv) significantly decreased the amplitudes of NVCs to 13.3 ± 1.3 cmH2O (P <0.01, n = 6) and the number of NVCs to 2.6 ± 0.6 (P <0.05, n = 6), whereas
Comment
The present study revealed that the protein and mRNA levels of ET-1 in the bladder are significantly increased in chronic SCI rats compared with spinal cord intact rats and that inhibition of ETA receptors, but not ETB receptors, suppressed bladder overactivity as evidenced by a reduction in the number and mean amplitude of NVCs in SCI rats. Thus, upregulation of the endothelin mechanism through increased expression of ET-1 and subsequent activation of ETA receptors in the bladder could
Conclusions
The present results indicate that inhibition of ETA receptors can inhibit nonvoiding bladder contractions associated with increased levels of ET-1 in the bladder in SCI rats. Thus, ETA receptor antagonists could be useful for the treatment of bladder overactivity in neurogenic diseases such as SCI.
References (15)
Bladder afferent pathway and spinal cord injury: possible mechanisms inducing hyperreflexia of the urinary bladder
Prog Neurobiol
(1999)- et al.
Differential roles of peripheral and spinal endothelin receptors in the micturition reflex in rats
J Urol
(2004) - et al.
Current and future pharmacological treatment for overactive bladder
J Urol
(2002) - et al.
Age-related changes in contractile responses of rabbit lower urinary tract to endothelin
J Urol
(2000) - et al.
Protective effect of an oral endothelin converting enzyme inhibitor on rat detrusor function after outlet obstruction
J Urol
(2004) - et al.
Effect of preemptive treatment of capsaicin or resiniferatoxin on the development of pre-micturitrion contractions after partial urethral obstruction in the rat
J Urol
(2003) - et al.
Neurophysiology of micturition and its modification in animal models of human disease
Cited by (14)
Pharmacologic therapy for the neurogenic bladder
2010, Urologic Clinics of North AmericaCitation Excerpt :Antiepileptic drugs have been shown to improve bladder function in animal113 and human114 studies of NGB. Other therapeutic targets that have shown promise thus far in animal models of NGB include cyclooxygenase inhibitor,115 an arginase inhibitor,116 endothelin-A receptor agonist,117 and gene therapy with glutamic acid decarboxylase.118 Antimuscarinic therapy is the mainstay in treatment for NGB with detrusor overactivity or poor compliance, with robust basic science and clinical data to support its use.
Novel treatments for men with lower urinary tract symptoms suggestive of benign prostate hyperplasia
2009, Journal of the Formosan Medical AssociationApplication and prospect of reconstructing bladder micturition reflex in neurogenic bladder after spinal cord injury
2024, Chinese Journal of Tissue Engineering ResearchThe Role of Gene Expression in Stress Urinary Incontinence: An Integrative Review of Evidence
2023, Medicina (Lithuania)
This work was supported by NIH Grants DK57267, DK68557 and HD39768. ET receptor antagonists were kindly provided by Abbott.
- 1
J.B. Nelson is a paid consultant to Abbott.