Relaxation of human detrusor muscle by selective beta-2 and beta-3 agonists and endogenous catecholamines.

OBJECTIVES: The goal of this study was to identify potent relaxant agents of the human detrusor muscle. Therefore, the relaxant effects of different selective beta (beta)-adrenoceptor agonists were examined. Also, the relaxant effects of the endogenous catecholamines were investigated to functionally characterize the beta-adrenoceptor subtype mainly responsible for adrenergic-mediated relaxation in the detrusor muscle of humans. METHODS: Experiments were performed on muscle strips of human detrusor suspended in a tissue bath. The tissue originated from patients who had undergone total cystectomy. The selective beta3-agonists BRL 37344, ZD 7114, and CGP 12177, the selective beta2-agonists terbutaline and clenbuterol, and the nonselective beta-agonist isoprenaline were investigated. Concentration-relaxation curves of the catecholamines were performed to determine the rank order of potency. RESULTS: The maximal relaxation induced by BRL 37344, ZD 7114, and CGP 12177 was 36%, 39%, and 37%, respectively. The corresponding pD2 values were 6.73, 4.82, and 6.09, respectively. Terbutaline and clenbuterol induced a maximal relaxation of 48% and 27%, and their pD2 value was 4.97 and 5.34, respectively. Isoprenaline, adrenaline, and noradrenaline induced a maximal relaxation of 72%, 58%, and 79%, respectively. The corresponding pD2 values were 6.18, 6.16, and 6.09, respectively. Because their differences were not significant, no rank order of potency was determined. CONCLUSIONS: Beta-adrenergic agonists are potent relaxant agents of the human detrusor muscle in vitro. Both beta2 and beta3-adrenoceptors contribute to adrenergic-mediated relaxation. Our results point to a slightly greater role for the beta3-receptor in human detrusor muscle.

Correlation between motor function and lower urinary tract dysfunction in patients with infantile cerebral palsy.

AIMS: The aim of this study was to evaluate urodynamic findings in patients with infantile cerebral palsy (CP) and to correlate the findings with impaired motor function. METHODS: We conducted a videourodynamic investigation on a highly select group of 29 patients (3-53 years). Motor function was assessed in each patient by the Gross Motor Function Classification System for CP (GMFCS). With this system, motor function is divided into five levels: patients in Level I have the most independent motor function and patients in Level V the least. The patients were divided into Group 1 (23 symptomatic patients with recurrent urinary tract infection or urinary incontinence) and Group 2 (6 asymptomatic patients). RESULTS: In Group 1, 21 patients (91%) had reduced compliance (0.6-16.4 ml/cmH(2)O) and 16 patients (70%) had increased DLPP (>40 cmH(2)O). Detrusor overactivity and pelvic floor overactivity were found in all 23 patients. In Group 2, two patients (33%) had reduced compliance (0.7 and 5.8 ml/cmH(2)O) and four (67%) had increased DLPP (>40 cm H(2)O). Detrusor overactivity and pelvic floor overactivity were observed in five patients (83%). Symptomatic patients showed higher GMFCS levels than asymptomatic patients. In the group of asymptomatic patients, there was no one classified as Levels IV or V, while there were no symptomatic patients classified as Level I. CONCLUSIONS: We conclude that urinary symptoms and pathological urodynamic findings increase along with the degree of motor function impairment shown by the GMFCS. Pathologic urodynamic findings can be found in both symptomatic and in asymptomatic patients.

Inhibitory effects of L- and T-type calcium antagonists on contractions of human detrusor muscle.

The inhibitory and relaxant effects of the L-type calcium antagonists nifedipine, nimodipine, verapamil and diltiazem, and of the T-type calcium antagonist mibefradil, on contractions of isolated human detrusor muscle were investigated. The tissue was obtained from 10 patients undergoing cystectomy due to bladder cancer. Effects of the calcium antagonists at different concentrations on the concentration-response curves for carbachol were investigated. Furthermore, concentration-relaxation curves were performed using potassium-precontracted muscle strips. All L-type calcium antagonists suppressed the mean concentration-response curve of carbachol significantly at a concentration of 10(-6) M. Mibefradil up to 10(-5) M did not significantly suppress it. Nifedipine significantly reduced the carbachol-induced maximum contraction to 75% and 44%, verapamil to 75% and 67% of the appropriate control value at concentrations of 10(-7) and 10(-6) M, respectively. Diltiazem reduced it insignificantly to 96% and 71% at the above-mentioned concentrations. The concentration-relaxation experiments revealed following pD2-values and maximum relaxations of nifedipine, nimodipine, verapamil and diltiazem, respectively: 6.23, 6.37, 5.66, 5.81 and 85%, 83%, 82%, 90%. Maximum relaxations and pD2-values were not significantly different from each other. The lowest concentration, for which a significant effect compared to control in Student;s t-test was found, amounted to 10(-10) M, 10(-9) M, 10(-7) M, 10(-6.5) M and 10(-4) M for nimodipine, nifedipine, diltiazem, verapamil and mibefradil, respectively. L-type calcium antagonists are very potent relaxant agents of the human detrusor muscle in vitro.