Idazoxan partially reverses alpha-2 (α₂)-inhibition of osmotic water permeability (P_f) in rat inner medulary collecting duct (IMCD)

To determine if idazoxan would reverse α₂-mediated inhibition of arginine vasopressin (AVP)-stimulated P_f in the terminal IMCD, Wistar rat IMCDs were isolated and perfused via standard methods and P_f was determined by measuring net fluid flux in the presence of a lumen-to-bath osmotic gradient. Two α₂ agonists, clonidine and dexmedetomidine, were used in separate studies (n=5 each study) to induce inhibition of AVP-stimulated P_f. All agents were added to the bath: AVP at 220 pM; clonidine, dexmedetomidine, and idazoxan at 100 nM. Results (P_f μm/sec, mean±sel are shown below. Control AVP AVP+Ag AVP+Ag+Ida Ag=Clonidine 2±1 177±12 * 30±2 * 79±5 * Ag = Dex 7±3 169±10 * 22±1 * 38±5 1 * & † - significantly different from previous period (p<.001) and (p<.05), respectively. Ag - α₂ agonist, Ida - idazoxan Idazoxan reversed clonidine- & dexmedetomidine-induced inhibition by 33% and 10%, respectively. In another set of experiments (n=5), the prototypical α₂ antagonist yohimbine, reversed dexmedetomidine-induced inhibition of P_f by 50%, and in a previous study (Rouch, AJ et al. Am. J. Physiol. 271, F150-157, 1996) the α₂ antagonist atipamezole reversed this inhibition ∼100%. These comparisons may lead to important information concerning different α₂ adrenoceptor subtypes.