Regulation of aquaporin-2 expression by the alpha(2)-adrenoceptor agonist clonidine in the rat

Aquaporin-2 (AQP-2), the major water channel responsible for water balance, has been shown to be regulated by the binding of vasopressin to V-2 vasopr essin receptors in the medullary collecting duct. alpha(2)-Adrenoceptor ago nists such as clonidine have been associated with an increase in free water clearance that was secondary to an inhibition of the ability of vasopressi n to increase cAMP levels in the collecting ducts. This investigation focus ed on the possibility that this increase in free water clearance following administration of an alpha(2)-adrenoceptor agonist was associated with a re duction in medullary AQP-2 expression. In the anesthetized rat, clonidine i ncreased urine flow rate (32 +/- 5 versus 137 +/- 16 mu l/min, p<.05) and f ree water clearance (-58 +/- 6 versus 3 +/- 8 ml/min, p<.05) compared with the group receiving the saline vehicle infusion. The increase in free water clearance with clonidine administration was associated with a reduction in whole kidney AQP-2 mRNA levels (282 +/- 25 versus 216 +/- 11 A units, p<.0 5). This decrease in water reabsorption was associated with a redistributio n of AQP-2 away from the luminal membrane of the medullary collecting duct to the cytosol. These effects were not secondary to changes in serum vasopr essin levels, as these were similar in the vehicle control and clonidine gr oups (59 +/- 5 pg/ml versus 64 +/- 7 pg/ml, p = NS). The rapid redistributi on of AQP-2 and the reduction in AQP-2 mRNA following clonidine administrat ion are consistent with the hypothesis that the alpha(2) adrenoceptor regul ates water excretion at least in part by effects on AQP-2.