To test the hypothesis that vasodilatory prostaglandins buffer the renal vasoconstrictor effects of endothelin-1 (ET-1) early in life, renal haemodynamic responses to ET-1 were measured in 2 groups of conscious, chronically instrumented lambs at 1-2 weeks of age (group I, n = 11) and 6 weeks of age (group II, n = 10). Lambs were pretreated with vehicle or 1 mg x kg(-1) indomethacin, a nonselective cyclooxygenase inhibitor, and renal haemodynamic effects were measured continuously for 1 min before (control) and 5 min after intra-arterial injection of 250 ng x kg(-1) ET-1. In group II lambs, there was a marked decrease in renal blood flow (RBF) and renal vascular conductance (RVC) elicited by ET-1 administration, as we have previously described. This response was not altered by vehicle or indomethacin pretreatment. In group I lambs, there was an initial increase but no decrease in RBF and RVC elicited by ET-1 administration, as we have previously described, and this response was also not altered by either vehicle or indomethacin. These results suggest that endogenously produced prostaglandins do not appear to modulate the renal haemodynamic effects of ET-1 in conscious lambs during postnatal maturation.

Previously, we showed in conscious lambs that pressor and renal haemodynamic responses to ANG II were greater at ∼six weeks as compared to newborns aged ∼one week. The present study investigated the roles of NO and PGs in modulating these responses to ANG II during post natal maturation. Two experiments were carried out at an interval of 24 h in two age groups of conscious, chronically instrumented lambs: ∼one week (N=8) and ∼six weeks (N=10). Acute arterial pressure (AP) and renal blood flow (RBF) responses to intra‐venous (I.V.) injection of EC50 ANG II were tested before and after administration of the L‐arginine analogue, NG‐nitro‐L‐arginine methyl ester (L‐NAME), in the presence of either vehicle (veh, experiment one) or indomethacin (indo, experiment two). In both age groups, L‐NAME had no effects on the AP and RBF responses to ANG II after veh. In contrast, after indo, AP and RBF responses to L‐NAME were increased at one week but not at six weeks. Therefore, there is an age‐dependent interaction between NO and PGs in buffering the pressor and renal haemodynamic effects of ANG II soon after birth.

Previously, we showed that ET‐1 elicits no renal vasoconstriction when administered to conscious newborn lambs (Smith et al. 2002, 2005). To test the hypothesis that vasodilatory prostaglandins modulate the renal haemodynamic response to ET‐1 during postnatal maturation, experiments were carried out in two age groups of conscious, chronically instrumented lambs: group I (8 – 17 days; n=4) and group II (32 – 57 days; n=6). Mean arterial (MAP) and venous pressures (MVP) as well as renal blood flow (RBF) were measured at 20 sec interval for one‐min before (Control, C) and five‐min after intra‐arterial (I.A.) injection of ET‐1 (250 ng/kg) both before and after intra‐venous (I.V.) injection of vehicle (Veh, experiment one) and the non‐selective cyclo‐oxygenase inhibitor, indomethacin (Indo, 1 mg/kg, experiment two). Renal vascular resistance (RVR) was calculated as (MAP‐MVP)/RBF. In group I, RVR was 41.1±9.4 mmHg·mL−1·min·g during C and 33.3±4.2 mmHg·mL−1·min·g at 1 min after ET‐1. In group II, RVR increased from 32.9±7.0 to 58.3±40.7 mmHg·mL−1·min·g at 1 min after ET‐1 and 61.3±33.8 mmHg·mL−1·min·g at 2 min. Neither Veh nor Indo had any significant effect on these RVR responses to ET‐1 in either group. Therefore, prostaglandins do not appear to modulate the renal haemodynamic responses to ET‐1 in conscious lambs during postnatal maturation.