Renal and renin responses to furosemide in conscious lambs during postnatal maturation

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Abstract
Despite the widespread use of furosemide in the treatment of various fluid and electrolyte disorders in the preterm and term human infant and child, the physiological effects of this potent diuretic agent on renal function and renin release during postnatal maturation are poorly understood. To test the hypothesis that the renal and renin responses to furosemide are altered during postnatal maturation, experiments were carried out in conscious chronically instrumented newborn lambs (11 ± 3 days, n = 7) and older lambs (28 ± 3 days, n = 6), at least 5 days after surgery under halothane anesthesia for placement of catheters. Renal function and plasma renin activity (PRA) were measured for 1 h before and 2 h after intravenous injection of furosemide (2 mg/kg; 0.2 mL/kg) or vehicle (0.2 mL/kg). Glomerular filtration rate (GFR) decreased after furosemide administration to both groups of lambs. However, the time course of this decrease in GFR was different, occurring sooner in older lambs (30 min) than in newborns (90 min). GFR remained significantly decreased after 150 min in both age-groups. The natriuretic and diuretic responses to furosemide were similar in newborns and older iambs, peak diuretic and natriuretic responses occurring within 30 min. PRA increased dramatically in both age-groups after furosemide; the response was accentuated in newborns. After 2 h, PRA was still elevated in newborns but returned towards control levels in older lambs. These data demonstrate that both the GFR and renin responses to furosemide are altered during ontogeny.Key words: renal function, diuretic, blood volume, renin–angiotensin system, renal nerves, neonate, baroreflex.