PROXIMAL TUBULAR FUNCTION IN TRANSGENIC MICE OVEREXPRESSING ATRIAL-NATRIURETIC-FACTOR

A transgenic mouse model in which atrial natriuretic factor (ANF) expression is targeted to the liver was used to study intrarenal adjustments to the chronically elevated hormone level. Such animals, designated TTR-ANF, are characterized by reduced arterial blood pressure but similar sodium excretion compared with nontransgenic siblings. Proximal tubular micropuncture gave the following results: single-nephron filtration rate = 12.7 +/- 1.1 vs. 15.6 +/- 1.9 nL/min (TTR-ANF versus nontransgenic, ns); end-proximal tubular fluid/plasma concentration ratio of inulin = 1.93 +/- 0.09 vs. 1.97 +/- 0.15 (ns); fractional reabsorption of sodium = 45.5 +/- 2.8 vs. 46.0 +/- 3.8% (ns); fractional reabsorption of chloride = 33.6 +/- 3.3 vs. 32.4 +/- 4.1% (ns). These data indicate that life-long elevation of plasma ANF concentration was not associated with significant alteration in single-nephron filtration rate and proximal tubular function. We conclude that compensatory antinatriuretic mechanisms, localized downstream from the proximal tubule, can prevent ANF natriuresis.