Beneficial effect of insulin-like growth factor-1 on hypoxemic renal dysfunction in the newborn rabbit.
Acute normocapnic hypoxemia can cause functional renal insufficiency by increasing renal vascular resistance (RVR), leading to renal hypoperfusion and decreased glomerular filtration rate (GFR). Insulin-like growth factor 1 (IGF-1) activity is low in fetuses and newborns and further decreases during hypoxia. IGF-1 administration to humans and adult animals induces pre- and postglomerular vasodilation, thereby increasing GFR and renal blood flow (RBF). A potential protective effect of IGF-1 on renal function was evaluated in newborn rabbits with hypoxemia-induced renal insufficiency. Renal function and hemodynamic parameters were assessed in 17 anesthetized and mechanically ventilated newborn rabbits. After hypoxemia stabilization, saline solution (time control) or IGF-1 (1 mg/kg) was given as an intravenous (i.v.) bolus, and renal function was determined for six 30-min periods. Normocapnic hypoxemia significantly increased RVR (+16%), leading to decreased GFR (-14%), RBF (-19%) and diuresis (-12%), with an increased filtration fraction (FF). Saline solution resulted in a worsening of parameters affected by hypoxemia. Contrarily, although mean blood pressure decreased slightly but significantly, IGF-1 prevented a further increase in RVR, with subsequent improvement of GFR, RBF and diuresis. FF indicated relative postglomerular vasodilation. Although hypoxemia-induced acute renal failure was not completely prevented, IGF-1 elicited efferent vasodilation, thereby precluding a further decline in renal function.
Prévot
Anne
A
Nephrology Unit, Department of Pediatrics, Lausanne University Medical Center (CHUV), Lausanne, Switzerland. prevotanne@hotmail.com
Julita
Monique
M
Tung
David K
DK
Mosig
Dolores
D
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000150:complications* / Q000188:drug therapy; D007275:Injections, Intravenous; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology*; D007674:Kidney Diseases / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D007677:Kidney Function Tests; D008136:Longevity / Q000187:drug effects; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects; D015996:Survival Rate; D016482:Urinalysis; D014664:Vasodilation / Q000187:drug effects
D007334:Insulin-Like Growth Factor I