Pharmacologic probing of renal development in the neonatal rat

This study was designed to examine the ontogeny of renal functions in the neonatal rat using various pharmacologic agents as probes. The renal responses of 2-, 6-, and 10-day-old rats to diuretic agents known to act on proximal tubules, loops of Henle and distal tubules were assessed. These included acetazolamide, furosemide, mercaptomerin, chlorothiazide and amiloride. Following administration of a diuretic agent, urine was collected at 90-min intervals for 6 h and urine volume, osmolality, chloride and pH were measured. Acetazolamide, furosemide, chlorothiazide and amiloride induced diuresis at each age indicating that the respective reabsorptive mechanisms were present and functional by 2 days of age. At all ages furosemide evoked a maximal response in eliminating the interstitial fluid gradient as indicated by the formation of an isosmotic urine in treated pups. However, the volume of the diuresis at 2 days of age was half those at 6 and 10 days, reflecting enhanced activity of the countercurrent multiplication apparatus in the maturing pups. Administration of mercaptomerin did not produce pharmacologic diuresis, but rather resulted in acute renal failure; although the nephrotoxicity was to a lesser extent in 2-day-old pups. The ability of the neonatal rat to respond to these pharmacologic probes demonstrates that the integrity of these renal functions is established in this species early in postnatal life.