Renal Effects of Atrial Natriuretic Peptide Infusion in Young and Adult Rats

ABSTRAm. The immature kidney appears to be less GFR, glomerular filtration rate responsive to atrial natriuretic peptide (ANP) than the MAP, mean arterial pressure mature kidney. It has been proposed that this difference UeC~pV, urinary cGMP excretion accounts for the limited ability of the young animal to UN,V, urinary sodium excretion excrete a sodium load. To delineate the effects of age on the renal response to exogenous ANP, Sprague-Dawley rats were anesthetized for study at 31-32 days of age, 3541 days of age, and adulthod. Synthetic rat A* was infused intravenously for 20 min at increasing doses ranging from 0.1 to 0.8 pg/kg/min, and mean arterial pressure, glomerular filtration rate, plasma ANP concentration, urine flow rate, and urine sodium excretion were measured at each dose. Since cyclic GMP acts as a second messenger for ANP action, urinary cyclic GMP excretion also was measured. Increasing doses of ANP caused a similar decrease in MAP at all ages studied, and increased glomerular filtration rate in adult but not young rats. Increasing the dose of ANP from 0.1 to 0.4 pg/kg/min caused a greater rise in urine flow and urinary cyclic GMP excretion in adult than young rats, and urine sodium excretion increased more in adults at all doses (p < 0.05). However, the rise in plasma ANP concentration also was greater in adults than in young rats (p < 0.05), indicative of greater systemic clearance of ANP in young animals. Increasing levels of plasma ANP concentration were correlated with a greater rise in urine flow in adult than young (31-32 day old) rats (p < 0.05), but there was no differential effect on urinary cyclic GMP excretion. We conclude that although the diuretic effect of ANP increases with age, the guanylate cyclase response to ANP does not change after 30 days of age in the rat. Decreasing clearance of ANP as rats age may be due to decreased enzymatic degradation of the peptide or reduced removal as a result of altered receptor binding. (Pediatr Res 24: 333-337,1988)