PURPOSE: Previous studies have shown that spinal alpha1-adrenoceptors can influence voiding in normal rats and in rats with outlet obstruction. Also, at the supraspinal level such receptors may be involved in voiding control. Therefore, we studied in rats the effects on cystometrography of intracerebroventricular administered alpha1-adrenoceptor antagonists. MATERIALS AND METHODS: Continuous cystometry was performed in conscious, freely moving rats with and without bladder outlet obstruction. Cystometric parameters were evaluated before and after intracerebroventricular drug administration. RESULTS: In normal rats intracerebroventricular administration of 8 nmol. kg.-1 prazosin (Pfizer Central Research, Sandwich, United Kingdom) or terazosin (Abbott Laboratories, Abbott Park, Illinois) (nonsubtype selective) caused no change in cystometric parameters. At 24 or 80 nmol. kg.-1 the 2 drugs significantly decreased voiding pressure and increased bladder capacity, voided volume and post-void residual urine volume. Administering vehicle had no effect. In rats with outlet obstruction the drug effects were significantly more pronounced than in normal animals (p <0.05), and urinary retention was produced in 50% of rats receiving prazosin. In normal rats the selective alpha1A-adrenoceptor antagonists KMD 3213 (0.8, 8 and 24 nmol. kg.-1) dose dependently depressed voiding pressure, and increased bladder capacity and voided volume, whereas BMY 7378 (selective for alpha1D-adrenoceptors) and A322312 (selective for alpha1B-adrenoceptors) at doses up to 80 nmol. kg.-1 had no effect. CONCLUSIONS: The results suggest that in normal rats and in rats with outflow obstruction volume induced bladder activity involves supraspinal alpha1-adrenoceptors. Bladder outlet obstruction seems to enhance the importance of these receptors. At least in normal rats the alpha1A-adrenoceptor subtype seems to mediate the effect.
PURPOSE: Previous studies have shown that spinal alpha1-adrenoceptors can influence voiding in normal rats and in rats with outlet obstruction. Also, at the supraspinal level such receptors may be involved in voiding control. Therefore, we studied in rats the effects on cystometrography of intracerebroventricular administered alpha1-adrenoceptor antagonists. MATERIALS AND METHODS: Continuous cystometry was performed in conscious, freely moving rats with and without bladder outlet obstruction. Cystometric parameters were evaluated before and after intracerebroventricular drug administration. RESULTS: In normal rats intracerebroventricular administration of 8 nmol. kg.-1 prazosin (Pfizer Central Research, Sandwich, United Kingdom) or terazosin (Abbott Laboratories, Abbott Park, Illinois) (nonsubtype selective) caused no change in cystometric parameters. At 24 or 80 nmol. kg.-1 the 2 drugs significantly decreased voiding pressure and increased bladder capacity, voided volume and post-void residual urine volume. Administering vehicle had no effect. In rats with outlet obstruction the drug effects were significantly more pronounced than in normal animals (p <0.05), and urinary retention was produced in 50% of rats receiving prazosin. In normal rats the selective alpha1A-adrenoceptor antagonists KMD 3213 (0.8, 8 and 24 nmol. kg.-1) dose dependently depressed voiding pressure, and increased bladder capacity and voided volume, whereas BMY 7378 (selective for alpha1D-adrenoceptors) and A322312 (selective for alpha1B-adrenoceptors) at doses up to 80 nmol. kg.-1 had no effect. CONCLUSIONS: The results suggest that in normal rats and in rats with outflow obstruction volume induced bladder activity involves supraspinal alpha1-adrenoceptors. Bladder outlet obstruction seems to enhance the importance of these receptors. At least in normal rats the alpha1A-adrenoceptor subtype seems to mediate the effect.