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

A transgenic mouse model in which atrial natriuretic factor (ANF) expr ession is targeted to the liver was used to study intrarenal adjustmen ts to the chronically elevated hormone level. Such animals, designated TTR-ANF, are characterized by reduced arterial blood pressure but sim ilar sodium excretion compared with nontransgenic siblings. Proximal t ubular micropuncture gave the following results: single-nephron filtra tion rate = 12.7 +/- 1.1 vs. 15.6 +/- 1.9 nL/min (TTR-ANF versus nontr ansgenic, ns); end-proximal tubular fluid/plasma concentration ratio o f inulin = 1.93 +/- 0.09 vs. 1.97 +/- 0.15 (ns); fractional reabsorpti on of sodium = 45.5 +/- 2.8 vs. 46.0 +/- 3.8% (ns); fractional reabsor ption of chloride = 33.6 +/- 3.3 vs. 32.4 +/- 4.1% (ns). These data in dicate that life-long elevation of plasma ANF concentration was not as sociated with significant alteration in single-nephron filtration rate and proximal tubular function. We conclude that compensatory antinatr iuretic mechanisms, localized downstream from the proximal tubule, can prevent ANF natriuresis.