STUDIES OF AUTONOMIC RECEPTOR FUNCTION IN CANINE URETHRA

Abstract

The function of autonomic receptors was studied using an isometric in vitro technique and urethral smooth muscle strips isolated from adult female dogs. The urethral pressure profile measurement method of Brown and Wickham was also employed with some modifications in female dogs. All agents used were intravenously injected.
In in vitro studies, noradrenalin and adrenalin produced a dose-dependent contraction which was blocked by phentolamine. The contraction in the transversal strips tended to be stronger than that in the longitudinal strips. Isoproterenol caused a weak relaxation which was blocked by propranolol. Acetylcholine provoked a weak contraction which was blocked by atropine. These results indicate that the urethral smooth muscle contain alpha- and beta-adrenergic receptors and muscarinic cholinergic receptor, and there is a dominancy of alpha-adrenergic receptor in reaction.
Noradrenalin produced a significant increase of intra-pressure of the midurethra in the urethral pressure profile and this response was reduced by phentolamine. Isoproterenol produced a significant decrease of the urethral pressure and this response was reduced by propranolol. The reaction to acetylcholirte was small and inconstant. Phentolamine induced a significant (approximately 62%) decrease of the urethral pressure, while the effects of propranolol and atropine were smaller. Hexamethonium also induced a significant decrease of the urethral pressure (approximately 37%). From these results, it is suggested that the urethral resting pressure is maintained mainly by the alphaadrenergic receptor activity.
Papaverine induced a significant decrease of the urethral pressure (approximately 41%). This agent abolished the increased pressure maintained by continuous drip infusion of noradrenalin, however, it showed a slight effect on the transient increase response to one shot injection of noradrenalin. The results suggest that the urethral pressure response to noradrenalin is mediated via alpha-adrenergic receptors in the urethral smooth musculature.
Changes of the urethral pressure in relation to vesical distension and urination were studied with simultaneous recording of intravesical pressure by means of cystostomy under various conditions. Along with vesical distension, the urethral pressure increased gradually. With the onset of vesical contraction consequent to micturition reflex, the urethral pressure decreased. After treatment with gallamine, both the increase and decrease responses remained although these responses were reduced. After treatment with phentolamine, the responses were reduced significantly, while they were abolished almost completely in dogs concomitantly with both agents. Little effect of propranolol on the responses was observed. These results indicate that the urethral function during a collecting phase of the urinary bladder and micturition can be achieved not only by the urethral striated musculature but also by the smooth musculature, and the latter is mainly controlled by the alpha-adrenergic receptor mechanism.