Micturition in the unanesthetized rat: spinal vs. peripheral pharmacology of the adrenergic system

The pharmacology of the spinal and peripheral adrenergic receptor-subtypes controlling the micturition reflex was studied in a chronic unanesthetized rat model by continuous infusion of saline in the bladder and cystometrography after intrathecal (i.t.) and i.p. injections, respectively. Due to the absence of a catheter in the urethra, the bladder contraction-sphincter relaxation coupling could be assessed very precisely. For each agent tested in this study, dose-response curves were established. Norepinephrine (i.p.), methoxamine (i.p.) and ST-91 (i.p. and i.t.) produced an increase in frequency of bladder contraction. A decrease in frequency was observed after i.p. injection of isoproterenol (30 micrograms) and terbutaline (300 micrograms). Phentolamine, yohimbine, propranolol (i.p. and i.t.), isoproterenol (i.t.) and methoxamine (i.t.) had little or no effects on frequency of contraction at the highest doses examined. In addition, norepinephrine (i.p.), isoproterenol (i.p. and i.t.), ST-91 (i.p.), terbutaline (i.p.), phentolamine (i.p.) and yohimbine (i.p.) produced some relaxation of the bladder outlet. Methoxamine (i.p.) produced an increase in tone of the outlet. Propranolol (i.p. and i.t.), methoxamine (i.t.), ST-91 (i.t.), phentolamine (i.t.) and yohimbine (i.t.) had little or no effects on the tone of the bladder outlet at the highest doses examined. Those observations suggest that peripherally, catecholamines modulate the frequency of bladder contraction (increase through alpha-1 and alpha-2 receptors; decrease through beta-2 receptors), and the tonic activity of the bladder outlet (increase in tone through alpha-1 receptors; relaxation through alpha-2 and beta-2 receptors). At the spinal level, noradrenergic systems appear to modulate the frequency of contraction and sphincter tone through alpha-2 receptors. Isoproterenol effects after i.t. injection are thought to be due to systemic distribution. However, absence of effects after i.t. injection of adrenergic antagonists suggests that spinal adrenergic systems might not be active during a normal volume-evoked micturition reflex, but might be activated in special circumstances, such as the voluntary act of retaining urine.