Dietary sodium restriction increased plasma aldosterone levels comparably in both wild-type and angiotensinogen-deficient mice, revealing a powerful angiotensin-independent mechanism driven by potassium.
Does dietary sodium restriction induce hyperaldosteronism independently of angiotensin via a potassium-dependent mechanism in mice?
Hyperaldosteronism during dietary sodium restriction can occur via a powerful angiotensin-independent, potassium-dependent mechanism.
Absolute Event Rate: 774% vs 17%
p-value: p=<0.05
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.
Okubo et al. (Sat,) conducted a other in Secondary Hyperaldosteronism. Low sodium diet vs. Normal sodium diet (0.46% Na) was evaluated on Plasma aldosterone concentration (ng/dl) in Agt-/- mice (p=<0.05). Dietary sodium restriction increased plasma aldosterone levels comparably in both wild-type and angiotensinogen-deficient mice, revealing a powerful angiotensin-independent mechanism driven by potassium.
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