Alpha 2-adrenergic-mediated inhibition of water and urea permeability in the rat IMCD

These studies were conducted to determine whether the alpha 2-agonists epinephrine and dexmedetomidine inhibit osmotic water permeability (Pf) and urea permeability (Pu) in the rat inner medullary collecting duct (IMCD). Wistar rat IMCD segments were perfused via standard methods, and Pf and Pu were determined in separate studies. The control period was followed by adding 220 pM arginine vasopressin (AVP) or 10(-4) M dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP) to the bath. Epinephrine or dexmedetomidine, both at 1 microM, was then added to the bath, and this period was followed by adding 1 microM atipamezole, a selective alpha 2-antagonist. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine was present in all experiments with DBcAMP. Epinephrine inhibited AVP- and DBcAMP-stimulated Pf by 90% and 80%, respectively. Dexmedetomidine inhibited AVP- and DBcAMP-stimulated Pf by 98% and 97%, respectively. Epinephrine inhibited AVP- and DBcAMP-stimulated Pu by 70% and 60%, respectively. Dexmedetomidine failed to affect Pu. Atipamezole reversed all inhibitory effects. These data confirm an alpha 2-mediated mechanism in the IMCD that modulates Pf and Pu, and they indicate that inhibition occurs via post-cAMP cellular events.