Experimental evidence for a central nervous system site of action in the effect of alpha-adrenergic blockers on the external urinary sphincter.

The present study was done to test the hypothesis that alpha-adrenoceptor blocking drugs (phentolamine and prazosin) could interfere with somatic control of the external sphincter through an action in the central nervous system. Stimulation of the hypogastric nerve in the chloralose-anesthetized cat caused a urethral constriction which could be antagonized by alpha-receptor blockers. However, the constriction produced by stimulation of the S1 or S2 ventral root was completely resistant to alpha blockade. The drugs therefore had the expected action against sympathetic stimulation of the urethra but had no peripheral effect on the somatic component. The central effect of these drugs was investigated by recording urethral perfusion pressure responses, or compound action potentials on the central cut end of the pudendal nerve, evoked by stimulation of the contralateral pudendal or pelvic nerve. The urethral constriction produced by stimulation of the central cut end of 1 pudendal nerve was antagonized by both prazosin and phentolamine. Action potentials evoked on the pudendal nerve by stimulation of the central cut end of the contralateral pudendal or pelvic nerve were substantially inhibited by prazosin. Phentolamine produced a more variable blockade of the pudendal-pudendal reflex. The results strongly indicate that these alpha-adrenoceptor antagonists and especially prazosin can influence pudendal nerve-dependent urethral responses through a central nervous system action and not through a peripheral mechanism.