ALPHA(2)-ADRENERGIC-MEDIATED INHIBITION OF WATER AND UREA PERMEABILITY IN THE RAT IMCD

These studies were conducted to determine whether the alpha(2)-agonist s epinephrine and dexmedetomidine inhibit osmotic water permeability ( P-f) and urea permeability (P-u) in the rat inner medullary collecting duct (IMCD). Wistar rat IMCD segments were perfused via standard meth ods, and P-f and P-u were determined in separate studies. The control period was followed by adding 220 pM arginine vasopressin (AVP) or 10( -4) NI dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP) to the b ath. Epinephrine or dexmedetomidine, both at 1 mu M, was then added to the bath, and this period was followed by adding 1 mu M atipamezole, a selective alpha(2)-antagonist. The phosphodiesterase inhibitor 3-iso butyl-1-methylxanthine was present in all experiments with DBcAMP. Epi nephrine inhibited AVP- and DBcAMP-stimulated P-f by 90% and 80%, resp ectively. Dexmedetomidine inhibited AVP- and DBcAMP-stimulated P-f by 98% and 97%, respectively. Epinephrine inhibited AVP- and DBcAMP-stimu lated P-u by 70% and 60%, respectively. Dexmedetomidine failed to affe ct P-u. Atipamezole reversed all inhibitory effects. These data con an at-mediated mechanism in the IMCD that modulates P-f and P-u, and the y indicate that inhibition occurs via post-cAMP cellular events.