In adult animals and humans, activation of kappa-opioid receptors results in a diuresis. The aim of the present study was to investigate whether kappa-opioids are also diuretic early in life and whether this is altered during postnatal maturation. Therefore, the renal effects of the kappa-opioid-receptor agonist U-50488H were measured in two separate age groups of conscious lambs at two stages of postnatal maturation (approximately 1 wk and approximately 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 kappa-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 kappa-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 kappa-opioid receptors early in life may lead to alterations in fluid balance.
The purpose of this study was to investigate in developing animals, the cardiovascular responses to severe hemorrhage at which compensatory mechanisms fail and when blood pressure remains decreased after blood loss. Two groups of conscious lambs (Group I: one to two weeks, N = 7; group II: six to seven weeks, N = 7) were studied. Mean arterial pressure, systolic and diastolic pressures, and heart rate were measured for 20 min before (Control, C) and for 60 min after a fixed hemorrhage of 30% of blood volume. The arterial baroreflex control of heart rate was assessed before (C), and at 30 and 60 min intervals after hemorrhage. Mean arterial pressure decreased for up to 60 min after hemorrhage in both groups of lambs. In group I, heart rate decreased from 200 ± 29 (C) to 164 ± 24 beat min−1 at 30 min then increased to 232 ± 45 beat min−1 at 60 min, whereas heart rate remained unaltered in group II. With respect to the arterial baroreflex control of heart rate, by 30 min after hemorrhage in group I, there was a decrease in the heart rate range over which the baroreflex operates (P1) from 192 ± 13 (C) to 102 ± 9 beats min−1; by 60 min after hemorrhage, there was a decrease in minimum heart rate (P4) from 72 ± 10 (C) to 32 ± 25 beats min−1. In group II, P1 decreased to a lesser extent than group I from 134 ± 21 (C) to 82 ± 10 beats min−1 at 30 min; minimum heart rate (P4) decreased from 40 ± 15 (C) to 24 ± 9 and 20 ± 13 beats min−1 at 30 and 60 min, respectively. These results provide the first assessment of the arterial baroreflex control of heart rate following blood loss and new evidence that the cardiovascular responses to severe hemorrhage are developmentally regulated.
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