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RENAL HEMODYNAMICS AND CARDIORENAL INTEGRATION

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

Departments of Physiology and Biophysics/Medicine, University of Calgary, Calgary, Alberta, Canada

Submitted 11 December 2006 ; accepted in final form 28 March 2007

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 -opioid-receptor 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.

5'-guanidinonaltrindole; newborn; renal function; kidney