Selectivity of oxymetazoline for urethral pressure vs blood pressure in the anaesthetized female rabbit

Objective: The aim of this study was to test alpha-adrenergic reference ago nists for tissue selectivity in the urethra and to pharmacologically charac terize the functional alpha-adrenoceptor type of the female rabbit urethra in vivo. Material and Methods: The effect of alpha-adrenergic agonists and antagonists on the urethral pressure was compared with that on blood pressu re and heart rate measured simultaneously in the anaesthetized female rabbi t. Results: Oxymetazoline, NS-49, phenylephrine and phenylpropanolamine enh anced the urethral pressure in a dose-dependent manner. Phenylephrine and p henylpropanolamine also enhanced the blood pressure with significantly lowe r ED50 (dose that gives half of the maximal enhancing effect) values than f or the urethral pressure. This was in contrast to oxymetazoline and NS-49. The ED50 values for oxymetazoline on urethral pressure, and systolic and di astolic blood pressure were 0.00067, 0.0030 and 0.0020 mg/kg, respectively. The ED50 values for NS-49 on urethral pressure, and systolic and diastolic blood pressure were 0.019, 0.21 and 0.18 mg/kg, respectively. Clonidine an d UK 14,304 had no effect on urethral or blood pressure. The oxymetazoline- evoked increase in urethral pressure was inhibited by WB-4101 with an ID50 (dose that gives half of the inhibitory effect) significantly lower than th at for rauwolscine. Conclusions: The results suggest that in the female rab bit in vivo activation of alpha(1)-adrenoceptors increased the urethral pre ssure. Phenylephrine and phenylpropanolamine, in contrast to oxymetazoline and NS-49, selectively enhanced blood pressure as compared with urethral pr essure. Provided that the present results also have validity in humans, it would seem possible to develop urethra-selective drugs for treatment of str ess incontinence with few or no cardiovascular side-effects.