Effect of saline infusion on kidney and collecting duct function in atrialnatriuretic peptide (ANP) gene "knockout" mice

Atrial natriuretic peptide (ANP) is thought to play a role in renal regulat ion of salt balance by reducing tubular reabsorption of sodium and chloride . Therefore, in the chronic absence of this hormone, a defect of salt excre tion should be evident. We used an ANP gene deletion model to test this pre mise. F-2 homozygous mutant mice (-/-) and their wild-type littermates (+/) were fed an 8% NaCl diet prior to an acute infusion of isotonic saline. A rterial blood pressures, renal excretions of salt and water, as well as col lecting duct transport of fluid and electrolytes were measured. Pressures w ere significantly higher in -/- compared with +/+ mice (139 +/- 4 vs. 101 /- 2 mmHg; I mmHg = 133.3 Pa). There was no difference in glomerular filtra tion rate (-/- = 0.84 +/- 0.06; +/+ = 0.81 +/- 0.04 ml.min(-1).g(-1) kidney weight). In the collecting duct, sodium and chloride reabsorptions were si gnificantly higher in the -/- group than in the +/+ group. As a result, nat riuresis and chloruresis were relatively reduced (UNaV: -/- = 8.6 +/- 1.1; +/+ = 14.0 +/- 1.1; UClV: -/- = 10.1 +/- 1.4; +/+ = 16.0 +/- 1.1 mu mol.min (-1).g(-1) kidney weight). We conclude that the absence of endogenous ANP a ctivity in mice on a high-salt diet subjected to acute saline infusion caus es inappropriately high reabsorption of sodium and chloride in the medullar y collecting duct, resulting in a relative defect in renal excretory capaci ty for salt.