Physiological Consequences of Early Neonatal Growth Retardation: Effects of alpha-Difluoromethylornithine on Renal Growth and Function in the Rat

摘要

The physiological consequences of early neonatal growth retardation in the kidneywere investigated using DFMO (alpha-difluoromethylornithine), a specific irreversible inhibitor of ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines. The study administered 500 mg/kg/day DFMO, or saline, to Sprague-Dawley rat pups from the day of birth through postnatal day (PD) 6 and evaluated renal function on PD 4, 7, 10, and 13 using tests of basal renal clearance and urinary concentrating ability. Kidney weights and gross pathology were also obtained. On PD 39, serum chemistries and organ weights were determined. In a second experiment, the study evaluated concentrating ability on PD 7-10, and basal renal function, concentrating ability, diuretic response, serum chemistries and organ weights on PD 132-140. DFMO selectively inhibited renal growth, but did not inhibit glomerular and tubular functional maturation. The rates of filtration and reabsorption (per g renal tissue), and concentrating ability were increased in treated pups. The renal growth retardation induced by neonatal administration of DFMO was associated with an apparent precocious maturation of function in the early postnatal period and dysfunction in adulthood, thus demonstrating that the physiological consequences of growth retardation are not always obvious and predictable, and must be evaluated on a case by case basis.