Angiotensin-independent mechanism for aldosterone synthesis during chronic extracellular fluid volume depletion.

Okubo S, Niimura F, Nishimura H, Takemoto F, Fogo A, Matsusaka T, Ichikawa I
J Clin Invest. 1997 99 (5): 855-60

PMID: 9062342 · PMCID: PMC507892 · DOI:10.1172/JCI119249

Wild-type (Agt+/+) and homozygous angiotensinogen deletion mutant (Agt-/-) littermates were placed on normal (NS) or low Na diet (LS) for 2 weeks. Plasma aldosterone levels (P(aldo)) were comparable during NS, and similarly elevated during LS in Agt+/+ and Agt-/-. Moreover, in both, the elevation in P(aldo) was accompanied by marked increase in adrenal zona glomerulosa cells and adrenal P450aldo mRNA. Agt-/- mice were distinguished from Agt+/+ mice by their higher plasma K level, by approximately 1.5 and approximately 3.8 mEq/liter during NS and LS, respectively. Within the Agt-/- group, P(aldo) was directly proportional to plasma K. The importance of K for the hyperaldosteronism during dietary Na restriction was verified by the observation that superimposition of K restriction led to hypotension in Agt+/+ and uniform death in Agt-/- mice along with a reduction in P(aldo) by 75 and 90%, respectively. Thus, suppression of potassium, but not angiotensin, led to a marked attenuation of hyperaldosteronism during dietary Na restriction. Therefore, (a) a powerful angiotensin-independent mechanism exists for the hyperaldosteronism during LS; (b) high K is a central component of this mechanism; (c) contrary to current belief, the tonic effect of high K on aldosterone synthesis and release does not require an intact renin-angiotensin system; and (d) normally, intermediary feedback signals for hyperaldosteronism, i.e., both hypotension and high K, are effectively masked by aldosterone actions.

MeSH Terms (23)

Adrenal Glands Aldosterone Angiotensin II Angiotensinogen Animals Blood Pressure Blotting, Northern Cytochrome P-450 CYP11B2 Diet, Sodium-Restricted Extracellular Space Genetic Engineering Glyceraldehyde-3-Phosphate Dehydrogenases Hypotension Mice Mice, Mutant Strains Mixed Function Oxygenases Potassium Renin-Angiotensin System RNA, Messenger Sequence Deletion Signal Transduction Sodium Zona Glomerulosa

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