α₁‐ and α₂‐Adrenoceptor hyporesponsiveness in isolated bisected vas deferens of bile duct‐ligated rats

Abstract

It has been suggested that cholestasis accompanied with changes in autonomic balance and hyporesponsiveness in muscarinic and adrenergic receptors of some organs, e.g. cardiovascular system. Increased plasma levels of epinephrine and norepinephrine has been shown during cholestasis suggesting augmented activity of sympathetic nervous system. In this study we evaluate both alpha(1) and alpha(2) responsiveness in isolated rat vas deferens, as a tissue with rich adrenergic innervations. Epididymal and prostatic halves of vas deferens responsiveness have been studied to phenylephrine and clonidine respectively in three groups of un-operated, sham-operated (sham), and bile duct-ligated (BDL) rats. Our results indicate that in vas deferens of BDL animals, the concentration-response curve of both phenylephrine and clonidine shifted to rightward compared to control group, while the position of concentration-response curve of sham group did not change significantly (P > 0.05). EC(50) of phenylephrine and IC(50) of clonidine were increased showing a decreased responsiveness of tissue to phenylephrine (P < 0.05) and clonidine (P < 0.001) in BDL rats. In this study, both subtype of alpha-adrenoceptors (alpha(1) and alpha(2)) has been studied in cholestatic rat vas deference. Our results showed that cholestasis induce hyporesponsiveness to phenylephrine and clonidine. These results are consistent with previous reports, suggesting the hyporesponsiveness of alpha(1)-adrenoceptors in pulmonary artery and papillary muscle and mesenteric beds. Our conclusion is that the cholestasis induces hyporesponsiveness to phenylephrine and clonidine in epididymal (alpha(1)-adrenoceptors) and prostatic (alpha(2)-adrenoceptors) halves of rat vas deferens respectively. Although the logical explanation to this hyporesponsiveness is the down regulation but it has been suggested that it is not because of down regulation.