Effect of Increased Potassium Intake on Adrenal Cortical and Cardiovascular Responses to Angiotensin II: A Randomized Crossover Study

BACKGROUND: Increased potassium intake lowers blood pressure in patients with hypertension, but increased potassium intake also elevates plasma concentrations of the blood pressure‐raising hormone aldosterone. Besides its well‐described renal effects, aldosterone is also believed to have vascular effects, acting through mineralocorticoid receptors present in endothelial and vascular smooth muscle cells, although mineralocorticoid receptors‐independent actions are also thought to be involved. METHODS AND RESULTS: To gain further insight into the effect of increased potassium intake and potassium‐stimulated hyperaldosteronism on the human cardiovascular system, we conducted a randomized placebo‐controlled double‐blind crossover study in 25 healthy normotensive men, where 4 weeks treatment with a potassium supplement (90 mmol/day) was compared with 4 weeks on placebo. At the end of each treatment period, we measured potassium and aldosterone in plasma and performed an angiotensin II (AngII) infusion experiment, during which we assessed the aldosterone response in plasma. Hemodynamics were also monitored during the AngII infusion using ECG, impedance cardiography, finger plethysmography (blood pressure‐monitoring), and Doppler ultrasound. The study showed that higher potassium intake increased plasma potassium (mean±SD, 4.3±0.2 versus 4.0±0.2 mmol/L; P=0.0002) and aldosterone (median [interquartile range], 440 [336–521] versus 237 [173–386] pmol/L; P<0.0001), and based on a linear mixed model for repeated measurements, increased potassium intake potentiated AngII‐stimulated aldosterone secretion (P=0.0020). In contrast, the hemodynamic responses (blood pressure, total peripheral resistance, cardiac output, and renal artery blood flow) to AngII were similar after potassium and placebo. CONCLUSIONS: Increased potassium intake potentiates AngII‐stimulated aldosterone secretion without affecting systemic cardiovascular hemodynamics in healthy normotensive men. REGISTRATION: EudraCT Number: 2013‐004460‐66; URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02380157.