Age-Related Changes in Contractile Responses of Rabbit Lower Urinary Tract to Endothelin

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

“…The highest density of binding sites appeared to be in vessels and the outer muscle layer (Garcia-Pascual et al, 1990). Binding sites for both ET A and ET B receptors were demonstrated , but ET A receptors were located only in the smooth muscle, whereas ET B receptors were found both in the urothelium and in the smooth muscle layers (Wada et al, 2000;Afiatpour et al, 2003). Garcia-Pascual et al (1990) showed that in isolated urethral smooth muscle, ET-1 caused concentration-related, slowly developing contractions.…”

Pharmacologic Targets on the Female Urethra

“…Functional importance of tachykinins in the etiology of urethral instability has to be validated with future research. Endothelins Endothelin (ET) receptors were shown in the urethral smooth muscle and urothelium in various animals [115][116][117] . ET-1 subtype was demonstrated to cause urethral smooth muscle contractions via ET-A receptors in the rabbit [118,119] .…”

Endothelin ETB Receptors Are Involved in the Relaxation to the Pig Urinary Bladder neck

“…Endothelin ET A receptors play an essential role in the contraction induced by ET‐1 in the lower urinary tract smooth muscle of several species, including human. Thus, ET A receptors mediate ET‐1‐induced contraction in human and rabbit detrusor and in the rabbit bladder base and urethra7–10 and are involved in the ET‐1 induced elevation of dog non‐prostatic and prostatic urethral pressure 10. In addition to the ET A receptor, an ET B receptor population with lesser functionality has also been involved in the ET‐1 elicited contraction of the guinea‐pig bladder 11.…”

“…Thus, in rabbit bladder outlet obstruction, an upregulation of endothelin ET A and ET B receptors has been described 12. Moreover, the maximal contractile responses to ET‐1 in rabbit bladder dome and trigone are reduced as a consequence of ageing,9 thus suggesting that both ET receptor subtypes play an important role in the pathophysiology of the lower urinary tract dysfunction and that therefore endothelin receptors and/or their intracellular signaling may be useful as targets in the treatment of urinary obstruction symptoms and in urinary incontinence 7, 10…”