Related Experiment Videos
Spinal and peripheral mechanisms contributing to hyperactive voiding in spontaneously hypertensive rats
K Persson1, R K Pandita, J M Spitsbergen
1Department of Clinical Pharmacology, Lund University Hospital, S-221 85 Lund, Sweden.
The American Journal of Physiology
|October 2, 1998
Summary
Spontaneously hypertensive rats exhibit bladder dysfunction due to altered noradrenergic control of the micturition reflex. Intrathecal doxazosin reduced bladder hyperactivity, suggesting central nervous system involvement.
Area of Science:
- Urology
- Neuroscience
- Pharmacology
Background:
- Spontaneously hypertensive rats (SHR) often display altered physiological functions compared to normotensive controls.
- Noradrenergic mechanisms play a crucial role in regulating the micturition reflex.
- Dysfunctional voiding and bladder hyperactivity are observed in certain hypertensive models.
Purpose of the Study:
- To investigate the influence of noradrenergic mechanisms on micturition in spontaneously hypertensive rats (SHR) compared to Wistar-Kyoto (WKY) rats.
- To assess the effects of doxazosin, a noradrenergic antagonist, on bladder function in vivo and in vitro.
- To elucidate the role of central and peripheral noradrenergic pathways in SHR bladder dysfunction.
Main Methods:
- Continuous cystometry was performed in vivo on anesthetized SHR and WKY rats.
- In vitro studies utilized isolated bladder and urethral tissues to assess responses to norepinephrine and electrical field stimulation.
- Pharmacological interventions included intrathecal and intra-arterial administration of doxazosin.
Main Results:
- SHR exhibited significantly lower bladder capacity and micturition volume, along with increased nonvoiding (unstable) bladder contractions compared to WKY rats.
- Intrathecal doxazosin markedly reduced nonvoiding contractions in SHR, an effect not observed with intra-arterial administration.
- Norepinephrine evoked weak contractions in SHR bladder strips, unlike WKY rat bladders, and significantly less inhibition of nerve-evoked contractions was observed in SHR.
Conclusions:
- Bladder dysfunction in SHR is associated with altered noradrenergic control of the micturition reflex.
- Increased smooth muscle and decreased neuronal responsiveness to norepinephrine contribute to SHR bladder alterations.
- The reduction in nonvoiding contractions by intrathecal doxazosin indicates that supraspinal and/or spinal structures are involved in the bladder hyperactivity of SHR.