Effect of potassium infusion on renal function in ANF-transgenic mice.
Transgenic mice expressing an ANF fusion gene in the liver were used to study renal function before and during an intravenous KCl load. These animals are characterized by a 10- to 20-fold elevation in plasma ANF concentration, and by a reduction in arterial blood pressure by 20-30 mm Hg, compared to nontransgenic littermates. Before the KCl infusion, renal excretions of fluid, sodium, potassium, and chloride were not different from corresponding values in the nontransgenic sibling mice. Glomerular filtration rates were slightly lower in the transgenic animals. During the KCl infusion, diuresis, saluresis, and kaliuresis were found in both groups. However, salt and water excretion, but not potassium excretion, were significantly greater in the transgenic group. In a separate series, plasma aldosterone concentrations were significantly higher in the transgenic, compared to the nontransgenic mice. These data are interpreted as indicating that antinatriuretic mechanisms, including aldosterone-dependent sodium reabsorption in the cortical collecting tubule, can counteract the effect of ANF to inhibit sodium reabsorption in the medullary duct system, thus allowing maintenance of salt balance. Furthermore, a reduced tubular flow rate at the aldosterone-sensitive site would ensure normal potassium excretion despite the elevated mineralocorticoid level. During KCl infusion, the known increase in tubular delivery of salt and water to the duct would allow full expression of the downstream ANF effect, accounting for the relatively greater diuresis and saluresis in the transgenic mice. We conclude that both renal and adrenal actions of ANF can be rendered ineffective by countervailing mechanisms, suggesting an explanation for the apparent lack of biological activity of endogenously elevated plasma NAF in some disease states.
Veress
A T
AT
Department of Physiology, University of Toronto.
Field
L J
LJ
Steinhelper
M L
ML
Sonnenberg
H
H
D000450:Aldosterone / Q000097:blood; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D004573:Electrolytes / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006400:Hematocrit; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D011188:Potassium / Q000097:blood / Q000494:pharmacology*; D011189:Potassium Chloride / Q000008:administration & dosage; D012964:Sodium / Q000097:blood; D014563:Urodynamics
D004573:Electrolytes; D000450:Aldosterone; D011189:Potassium Chloride; D009320:Atrial Natriuretic Factor; D012964:Sodium; D011188:Potassium