Effect of Endothelin on Bladder Contraction: Potential Role in Bladder Hyperactivity

Abstract

In the present study, we demonstrate that the intravenous infusion of endothelin-1 (3 and 10 ng/kg/min) causes a decrease in the mean micturition volume of rats in addition to an increase in mean arterial pressure. These effects are blocked by both the ET_A/ET_B-non-selective and the ET_A-selective endothelin antagonists SB 217242 and SB 247083 respectively (both 30 mg/kg). However, it was also observed that the ET_B-selective agonist sarafotoxin 6c (3 and 10 ng/kg/min) had similar effects on both mean arterial pressure and micturition volume. Initial experiments indicated that spontaneously hypertensive rats have a much lower mean micturition volume than normal rats. Binding studies comparing the total number and ratio of ET_A/ET_B receptors in spontaneously hypertensive, Wister-Kyoto and Sprague-Dawley rats revealed no significant differences in receptor expression. However, the magnitude of the response to endothelin-1 was greater in spontaneously hypertensive versus normal rats.

The urinary bladder of spontaneously hypertensive rat demonstrates bladder hypertrophy, inflammation, and fibrosis but not hyperplasia

“…Subsequent studies show that this strain of rats also has significant urological complications demonstrated as development of microscopic kidney stones and bladder calculi [3], hyperactive voiding [4, 5], a shorter filling phase and greater frequency of intravesical pressure rises [6]. SHR often shows an increase in voiding frequency and a decrease in bladder capacity and micturition volume [4, 7].…”

Bladder Endothelin-1 Receptor Binding of Bosentan and Ambrisentan

“…ET-1 is synthesized not only by smooth muscle cells in the urinary bladder, but also by epithelial cells and fibroblasts (2). Furthermore, the intravenous infusion of ET-1 was shown to cause a decrease in the mean micturition volume of rats in addition to an increase in mean arterial pressure (16 effects on various urinary dysfunctions including benign prostatic hyperplasia (17). The protective effect of an endothelin-converting enzyme inhibitor on rat detrusor function after outlet obstruction has also been demonstrated (18).…”

“…These studies clearly indicate the existence of functional receptors for endothelins in the bladder, which could be a promising target for the treatment of lower urinary tract symptoms. Bladder endothelin receptors have been briefly identified (3,15,16,19,20). However, bladder ET-1 receptor binding of endothelinreceptor antagonists used for the treatment of pulmonary arterial hypertension has not been examined in detail.…”

Emerging pharmacological targets in overactive bladder therapy: experimental and clinical evidences

“…I.v. ET-1 is able to decrease the micturition volume, an effect that could be blocked by ET-receptor antagonists [47]. The selective ET-A-antagonist, LU 302146, reduced the stimulation-induced pig bladder contraction in an atropine-inhibited way [48].…”