The current study was performed in 30 anesthetized and mechanically ventilated newborn rabbits to investigate the role of the endothelium-derived relaxing factor nitric oxide (NO) in the renal vasoconstriction observed during hypoxemia. Renal blood flow (RBF) and GFR were determined by the clearance of p-aminohippuric acid and inulin, respectively. In nine newborn rabbits (group 1), acute hypoxemia induced a significant decrease in RBF (-17 +/- 7%) and GFR (-11 +/- 6%). A second group of nine animals was used to determine the role of NO in regulating renal hemodynamics of the immature kidney in physiologic conditions. N omega-Nitro-L-arginine methyl ester (L-NAME), a NO synthesis inhibitor, significantly increased the renal vascular resistance by 31 +/- 9% and decreased RBF and GFR (-20 +/- 6% and -13 +/- 5%, respectively). Acute hypoxemia was induced in 12 additional newborn rabbits during L-NAME infusion (group 3) to define the role of NO in the renal vasoconstriction observed during hypoxemia. The changes in renal hemodynamics were greater in this group than in those induced by hypoxemia alone. The present results suggest that: 1) endogenous NO has a crucial role in maintaining basal renal perfusion, 2) the activity of NO synthase is maintained during acute hypoxemia, and 3) NO could blunt the effects of acute hypoxemia in the immature newborn rabbit kidney.

The current study was performed in 17 anesthetized and mechanically ventilated newborn rabbits to investigate the role of nitric oxide (NO) in the regulation of basal renal function of the immature kidney. Renal blood flow and glomerular filtration rate were determined by the clearance of p-aminohippuric acid and inulin, respectively. In 9 newborn rabbits (group 1), L-NAME, a NO synthesis inhibitor, significantly increased the renal vascular resistance by 31 ± 9% and decreased the renal blood flow by 20 ± 6%. The fraction of filtration significantly increased by 8 ± 5% despite a delayed decline in glomerular filtration rate by 13 ± 5%. Mean arterial pressure and heart rate were not altered. In 8 additional newborn rabbits (group 2), L-arginine, the physiological precursor of NO synthesis, partially reversed the renal hemodynamic changes induced by L-NAME. The present results demonstrate that the decrease in NO production induced by L-NAME (1) significantly affects the renal microcirculation of the immature newborn rabbit kidney and (2) predominantly increases the postglomerular renal vascular resistance. Endogenous NO thus appears to play a major role in maintaining the basal perfusion of the immature kidney.

ABSTRACT. The renal effects of endothelin-1 were investigated in 16 anesthetized and mechanically ventilated newborn rabbits. Renal blood flow and glomerular filtration rate were determined by the clearance of para-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In eight newborn rabbits, a bolus injection of 5 nmol.kg-' of endothelin-1 caused an initial fall in mean arterial blood pressure followed by a gradual, significant increase in mean arterial blood pressure that lasted for 45 min. The dramatic increase in renal vascular resistance (+28 f 4%) induced by endothelin led to a fall in glomerular filtration rate (-12 + 4%) and renal blood flow (-16 + 3%). In spite of the reduction of glomerular filtration rate and renal blood flow, urine flow and sodium excretion rates increased significantly (+20 f 5% and +49 f 9%, respectively). In eight additional newborn rabbits, a bolus injection of 1 nmol. kg-' of endothelin-a dose that usually induces marked renal and systemic vasoconstriction in adult models-did not affect systemic or renal hemodynamics. In conclusion, endothelin induces renal and systemic vasoconstriction and affects water and sodium homeostasis during the neonatal period. These effects occur under higher doses than those used in adult animals. This age difference in systemic and renal responsiveness is probably mediated by receptor immaturity and/or interference of high levels of counteracting hormones present during the neonatal period. (Pediatr Res 34: 120-123, 1993) Abbreviations CFR, glomerular filtration rate RBF, renal blood flow RPF, renal plasma flow FF, filtration fraction MBP, mean blood pressure RVR, renal vascular resistance PAH, paraaminohippuric acid V, urine flow rate UNaV, urinary sodium excretionThe immature kidney is exposed to various vasoactive systems such as the renin-angiotensin system, intrarenal adenosine, the prostaglandins, and atrial natriuretic peptide, which are hyper-

In the newborn rabbit, acute normocapnic hypoxemia increases the renal vascular resistance, leading to renal hypoperfusion and decreased glomerular filtration rate. Endothelin is a potent vasoconstrictor peptide, produced by vascular endothelial cells, which could play a role as a mediator of the hypoxemia-induced renal dysfunction. To test this hypothesis, experiments were performed in 24 anesthetized and mechanically ventilated newborn rabbits. Renal blood flow and glomerular filtration rate were determined by the clearance of p-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In 8 newborn rabbits (group 1), a bolus injection of 5 nmol·kg^––1 of endothelin caused a marked increase in mean blood pressure and renal vascular resistance leading to a significant fall in glomerular filtration rate (––12 ± 4%) and renal blood flow (––16 ± 3%). A second group of animals (n = 8) confirmed the neutralizing activity of the endothelin-1 antiserum in vivo. In spite of pretreatment with endothelin-1 antiserum, hypoxemia induced an increase in renal vascular resistance (+40 ± 18%; p < 0.05) associated with a significant fall in glomerular filtration rate (––18 ± 7%) and renal blood flow (––29 ± 6%) in 8 newborn rabbits (group 3). The present results suggest that endothelin-1 does not mediate the hypoxemia-induced renal changes.

The renal effects of dopexamine, a new dopaminergic agonist devoid of any α-adrenergic effect, were studied in 11 anesthetized newborn rabbits undergoing an acute hypoxemic normocapnie stress. Acute hypoxemia (PaO(2) = 41 mm Hg) was associated with a marked increase in renal vascular resistance and a consequent decrease in glomerular filtration rate and renal blood flow. These changes were not modified by the administration of dopexamine at 10 μg/kg/min. Failure of dopexamine to blunt the hypoxemia-induced vasoconstriction suggests vascular dopaminergic receptor immaturity.