Endothelin-1 and Nitric Oxide in the Pathogenesis of Urinary Tract Disorders Secondary to Bladder Outlet Obstruction

Abstract

Bladder outlet obstruction (BOO) is a common disorder that is associated with urinary tract symptoms. Nitric oxide (NO), synthesized by NO synthase (NOS) is a potent vasodilator that is present throughout the urinary tract and the corpus cavernosum. Endothelin-1 (ET-1) conversely is a potent vasoconstrictor peptide that is similarly distributed throughout the urinary tract. ET-1 and NO as well as possessing opposing actions regulate each other's synthesis. The disruption of the balance between ET-1 and NO is associated with various vascular pathologies. However, their potential roles in the pathogenesis of urinary tract disorders, secondary to BOO, is not well established. New Zealand White rabbits with BOO are considered to be a suitable model of the human condition. Hence, using this model, we systematically investigated the potential roles of ET-1 and NO in the pathogenesis of the various urological disorders associated with BOO. In this review we discuss the results of our studies, which support the concept that an imbalance between ET-1 and NO may be associated with the pathogenesis of urinary tract disorders secondary to BOO. We also discuss the potential clinical implications of this association. This review is based on the Bard Silver Medal Lecture given (by MAK) at the 2002 British Association of Urological Surgeons (BAUS) annual meeting.

The effect of chronic partial bladder outlet obstruction on corpus cavernosum smooth muscle and Rho‐kinase in rabbits

“…The disruption of the balance between ET-1 and NO is associated with various vascular pathogenesis. [19][20][21][22] Hence, after severe PBOO, generation of free radicals as well as imbalance between ET-1 and NO both could possibly contribute to the changes in penis structure and relaxation of CCSM. Though these hypotheses are mentioned, they are not being verified by this study.…”

Role of Phosphodiesterase Type 5 Inhibitor on Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms

“…10 NO mediates smooth muscle relaxation in the corpus cavernosum, prostate and bladder. [10][11][12] Phosphodiesterase 5 inhibitors (PDE5 Is), such as sildenafil, tadalafil and udenafil increase the concentration of cGMP in smooth muscle by blocking the PDE 5, facilitating erection of the penis, relaxation of the bladder neck and prostate leading to bladder emptying. Considering the high incidence of ED and BPH in aging men, the ability to treat both disorders with a single agent, such as a PDE5 I, would be in valuable.…”

Efficacy and safety of combination therapy with mirodenafil and α1-blocker for benign prostatic hyperplasia-induced lower urinary tract symptoms accompanied by erectile dysfunction: a multicenter, open-label, prospective study

“…[1][2][3][4] Other studies have also suggested that the same pathophysiological mechanisms may underlie both ED and BPH-induced LUTS (LUTS/BPH): these mechanisms may involve nitric oxide synthase/ nitric oxide pathways, endothelin-1, autonomic overactivity, rhokinase activity and a 1 -adrenergic receptors. [5][6][7] With regard to the latter, as a 1 -adrenergic blockers (a 1 -blockers) inhibit the a 1 -adrenergic receptors of smooth muscles of the prostate and bladder neck, and induce the relaxation of these muscles, these blockers alleviate LUTS. 8 In addition, when the activity of nitric oxide is improved by a PDE5i, erection is induced.…”