Renal responses to the -opioid-receptor agonist U-50488H in conscious lambs

Qi W, Ebenezar KK, Samhan MA, Smith FG. Renal responses to the -opioid-receptor agonist U-50488H in conscious lambs. Am J Physiol Regul Integr Comp Physiol 293: R162–R168, 2007. First published April 4, 2007; doi:10.1152/ajpregu.00863.2006.—In adult animals and humans, activation of -opioid receptors results in a diuresis. The aim of the present study was to investigate whether -opioids are also diuretic early in life and whether this is altered during postnatal maturation. Therefore, the renal effects of the -opioidreceptor agonist U-50488H were measured in two separate age groups of conscious lambs at two stages of postnatal maturation ( 1 wk and 6 wk) under physiological conditions. To evaluate whether the renal responses to U-50488H resulted from receptor-dependent effects, responses to U-50488H were also tested in the presence of the specific -opioid-receptor antagonist 5 -guanidinonaltrindole (GNTI). Urinary flow rate, free water clearance, and electrolyte excretions and clearances were measured for 30 min before and for 90 min after intravenous injection of U-50488H or vehicle. An increase in urinary flow rate accompanied by an increase in free water clearance occurred in response to administration of U-50488H but not vehicle. There were no effects of U-50488H on electrolyte excretions or clearances at either 1 or 6 wk of postnatal life. Although there were no effects of GNTI on any of the measured or calculated variables, the aforementioned diuretic response to U-50488H was abolished by pretreatment with GNTI in both age groups. We conclude that -opioid receptors are diuretic early in life and that this response does not appear to be altered as postnatal maturation proceeds. Therefore, these data provide evidence that activation of -opioid receptors early in life may lead to alterations in fluid balance.