Potassium‐Sensitive Hyperaldosteronism in Kcnmb1 −/− Mice (β1 KO)

Hypertension often results from elevated aldosterone (Aldo), which promotes renal Na reabsorption and K secretion (ROMK and BK). β1KO have defective renal K secretion and exhibit hypertension ‐ the latter thought to result from vascular smooth muscle dysfunction. BK are also in the zona glomerulosa cells, where they help regulate Aldo production. We hypothesized that the hypertension of β1KO results from inappropriate Aldo production in response to plasma [K]. Wild type (WT) and β1KO were fed a control (CK; 0.8%) or a high K (HK; 5.0%) diet for 10d. Additional groups were fed HK + Eplerenone (E; Aldo antagonist) or vehicle. Mean arterial blood pressure (mmHg) was greater in β1KO ‐ CK (134±17 vs 111±14) and was further increased in the β1KO ‐HK (149±12 vs 114±14) but reversed in β1KO ‐ HK+E (121±16 vs 113±16, p=NS). Compared to WT, β1KO ‐ CK had increased plasma [Aldo] (147±14 vs 107±6 pg/ml) which was further increased by HK (216±20 vs 145±17). β1KO ‐ HK (but not HK+E) exhibited volume expansion by increased body weights and reduced hematocrits. Plasma [K] (mM) was significantly increased in β1KO ‐ CK (4.4±0.1 vs 4.1±0.1) and ‐ HK (4.8±0.2 vs 4.3±0.3) compared to WT. HK+E increased plasma [K] in both WT and β1KO (6.0±0.2 vs 6.1±0.2, p=NS). The slope of the plasma [K] vs. [Aldo] relation was increased by 2‐fold in β1KO vs. WT. Conclusion: The hypertension of β1KO is partially due to elevated [Aldo], a condition that is exacerbated by HK diet.