Nitric oxide, formation and effects in the urogenital tract

Abstract

The aim of the thesis was to study the formation and effects of nitric oxide (NO) in the human urinary tract and in the male reproductive organs. In the human upper and lower urinary tract NO synthase activity was studied via the formation of radiolabeled L-citrulline from L-arginine. In the human upper urinary tract NO synthase activity was found in the renal pelvis and exogenous NO inhibited spontaneous rhythmic and tonic contractions in both the isolated renal pelvis and the ureter suggesting that NO is a modulator of renal myogenic pacemaker-induced peristalsis. In the human lower urinary tract NO synthase activity was high in the prostatic urethra, intermediate in the bladder neck and low in the detrusor which is in good agreement with the nerve-induced smooth muscle responses and the guanylate cyclase activity.

The results suggests that NO is the major mediator for neurogenic dilatation of the bladder neck and urethra during the micturition reflex. Estrogen and progesterone were shown to induce Ca2+-dependent NO synthase activity in the female guinea-pig urinary bladder suggesting that estrogen substitution, which reduces irritative bladder symptoms in elderly women, may act by increasing the Ca2+-dependent NO synthase activity in the lower urinary tract. Irritative bladder symptoms may be caused by various inflammatory conditions in the lower urinary tract. Since NO synthesis is increased during inflammation in several tissues we measured the luminal NO concentration in air from the human urinary bladder with chemiluminescence technique to study weather increased NO production is at hand in patients with inflammatory conditions in the lower urinary tract. Elevated levels of luminal NO concentrations were found in urinary bladders with inflammation due to interstitial cystitis and irradiation cystitis.

The analysis of NO in air from the urinary bladder may be a simple diagnostic method to identify patients with cystitis. In the human male reproductive tract NO synthase activity was high, with the highest activity in the seminal vesicle, prostate and vas deferens. NADPH-diaphorase staining showed a prominent staining of the secretory cells in the vas deferens, seminal vesicle, prostate and urethra but also in the testis and epididymis of man and guinea-pig. NO synthase activity in the secretory epithelium of the guinea-pig seminal vesicle was 6 times higher than in the muscle coat, suggesting that the major part of the NO synthase activity is localized in the secretory cells. NO synthase inhibitors blocked the secretion of fructose induced by carbachol and nerve stimulation, respectively. Furthermore, a NO donor increased the fructose secretion. The results suggests that NO formation is a functional step in the secretory response to muscarinic stimulation of the glandular cells of the seminal vesicle.

In conclusion, these findings suggest that NO is the mediator for neurogenic dilatation of the bladder neck and urethra during the micturition reflex. NO is also suggested as a cellular mediator of secretion in the male reproductive tract indicating an important role of NO in male fertility. Analysis of NO in air from the urinary bladder may be a simple method to identify patients with cystitis.