Role of Nitric Oxide in the Hypoxemia-Induced Renal Dysfunction of the Newborn Rabbit

Abstract

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.

Beneficial effect of insulin-like growth factor-1 on hypoxemic renal dysfunction in the newborn rabbit

“…These results are consistent with the observations reported for hypoxemia alone. They strengthen the notion of a vasomotor origin of the hypoxemia-induced insult on the immature kidney previously reported by our group [2][3][4][5][6] and suggest a role for IGF-1 deficiency in this complex phenomenon. In anesthetized adult rats given IGF-1, Baumann et al reported an increase in GFR, renal plasma flow and diuresis by 35%, 100% and 300%, respectively, whilst RVR decreased by 50%.…”

“…As we previously reported, acute normocapnic hypoxemia in newborn rabbits was associated with a significant increase in RVR and a concomitant decline in RBF, GFR, MAP and diuresis [3][4][5][6]25]. We formerly demonstrated that renal hypoperfusion has a vasomotor origin and that the underlying mechanisms involve the complex activation and interaction of vasoconstrictor and vasodilator factors acting on renal arterioles, including angiotensin II [5], adenosine [3,4], or NO [6].…”

“…This response was seen as early as 3 h after the beginning of incubation with IGF-1, which is a time-course consistent with our experiment. Our group previously demonstrated that L-NAME administration was accompanied by a worsening of the hypoxemia-induced renal vasoconstriction, suggesting that endogenous NO is functionally present in the immature kidney and that NOS activity is maintained during acute hypoxemia [6]. Moreover, endogenous NO maintains neonatal basal renal perfusion mainly through postglomerular renal vascular resistance [37].…”

“…We formerly demonstrated that renal hypoperfusion has a vasomotor origin and that the underlying mechanisms involve the complex activation and interaction of vasoconstrictor and vasodilator factors acting on renal arterioles, including angiotensin II [5], adenosine [3,4], or NO [6].…”

“…The pathophysiologic mechanisms of this vasomotor nephropathy involve numerous local and humoral vasoactive agents. Previous studies from our laboratory have demonstrated that hypoxemia induces an alteration in the balance of local vasomediators in the newborn rabbit's kidney, including the vasoconstrictors adenosine and angiotensin II [3][4][5], as well as the vasodilator nitric oxide (NO) [6].…”