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J Urol. 2004 Oct;172(4 Pt 1):1533-7.

Differential roles of peripheral and spinal endothelin receptors in the micturition reflex in rats.

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  • 1Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.

Abstract

PURPOSE:

We investigated the effects of endothelin (ET) receptor activation in the bladder and the spinal cord on the micturition reflex in urethane anesthetized rats.

MATERIALS AND METHODS:

The effects of ET receptor activation on bladder activity were examined during continuous infusion cystometrograms. ET-1 was administered intrathecally or intravesically in normal rats or rats pretreated with capsaicin. The effects of intravenous injection of the selective ETA receptor antagonist ABT-627, or selective ETB receptor antagonist A-192621 (Abbott Laboratories, Abbott Park, Illinois) intrathecal injection of the opioid receptor antagonist naloxone hydrochloride on changes in bladder activity induced by intravesical or intrathecal ET-1 administration were investigated.

RESULTS:

Intravesical injection of ET-1 (0.1 to 10 microM) induced detrusor overactivity, as evidenced by a decrease in intercontraction intervals, in a dose dependent manner. ET-1 induced detrusor overactivity was suppressed by intravenous application of ABT-627 (0.1 mg/kg) as well as capsaicin pretreatment but not by A-192621. In contrast, intrathecal injection of ET-1 (0.5 to 50 fmol) increased intercontraction intervals dose dependently and ET-1 at a higher dose (50 fmol) induced urinary retention. These inhibitory effects were antagonized by ABT-627 (10 mg/kg) and also by intrathecal application of naloxone but not by A-192621.

CONCLUSIONS:

These results indicate that the activation of ETA receptors in capsaicin sensitive C-fiber afferents in the bladder can induce detrusor overactivity, while ETA receptor activation in the spinal cord can inhibit the micturition reflex via activation of a spinal opioid mechanism. Thus, targeting peripheral ETA receptors could be an effective treatment for bladder overactivity and/or painful conditions.

PMID:
15371886
[PubMed - indexed for MEDLINE]
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