Blood pressure and fluid-electrolyte balance in ANF-transgenic mice on high- and low-salt diets

Transgenic mice overexpressing an atrial natriuretic factor (ANF) fusion gene (TTR-ANF) and their nontransgenic siblings were placed on a high- (8%) or low (< 0.008%)-salt diet for 14 days to determine whether the lifelong elevation of ANF in the transgenic animals compromised their ability to maintain fluid-electrolyte balance. Steady-state dietary intake and urinary output of sodium and chloride were not statistically different between TTR-ANF and control groups on either diet. By contrast, water intake and urine volume were markedly elevated in the TTR-ANF group on either diet. Arterial blood pressure, measured in anesthetized mice at the end of the dietary regimen, was significantly and similarly reduced in the TTR-ANF compared with control groups on either diet, although high salt intake was associated with increased pressure in both groups. Renal excretion of fluid and electrolytes was studied in the anesthetized mice before and after acute blood volume expansion. Although the absolute increase in fluid and electrolyte excretion was much greater on the high- than on the low-salt diet in both groups, TTR-ANF mice had an exaggerated response relative to controls on either diet. On the basis of these results, we conclude the following. 1) When they are stimulated, renal salt-conserving mechanisms are sufficiently powerful to overcome the expected natriuretic effects of chronic elevation of plasma ANF; however, the natriuretic potential of ANF can be expressed in the short term when the counterregulatory mechanisms are inactivated. 2) ANF exerts a chronic hypotensive effect that is independent of changes in renal salt excretion.(ABSTRACT TRUNCATED AT 250 WORDS)