Effect of Atenolol on Aldosterone/Renin Ratio Calculated by Both Plasma Renin Activity and Direct Renin Concentration in Healthy Male Volunteers

BACKGROUND: The most popular screening test for primary aldosteronism (PAL) is the plasma aldosterone to renin ratio (ARR). Medications, dietary sodium, posture, and time of day all affect renin and aldosterone levels and can result in false-negative or -positive ARR if not controlled. Opinions are divided on whether beta-adrenoreceptor blockers significantly affect the ARR. METHODS: Normotensive, nonmedicated male volunteers (n = 21) underwent measurement (seated, midmorning) of plasma aldosterone (by HPLC-tandem mass spectrometry), direct renin concentration (DRC), renin activity (PRA), cortisol, electrolytes, and creatinine and urinary aldosterone, cortisol, electrolytes, and creatinine at baseline, and after 1 wk (25 mg daily) and 4 wk (50 mg daily for three additional weeks) of atenolol. RESULTS: Compared with baseline, levels of aldosterone, DRC, and PRA were lower (P < 0.001) after both 1 and 4 wk [median (25-75th percentiles): baseline, 189 (138-357) pmol/liter, 40 (30-46) mU/liter, and 4.6 (2.7-5.8) ng/ml x h; 1 wk, 166 (112-310) pmol/liter, 34 (30-40) mU/liter, and 2.6 (2.0-3.1) ng/ml x h; 4 wk, 136 (97-269) pmol/liter, 16 (13-23) mU/liter, and 2.1(1.7-2.6) ng/ml x h, respectively]. ARR was significantly higher after 1 wk compared with baseline when calculated using PRA [61 (30-73) vs. 65 (44-130), P < 0.01] but not DRC [5 (4-7) vs. 5 (4-8)]. At 4 wk, ARR calculated by both PRA [78 (49-125)] and DRC [8 (6-14)] were significantly higher (P < 0.001) compared with baseline, and cortisol levels were significantly lower [92 (68-100) vs. 66 (48-91) ng/ml, P < 0.01]. There were no changes in plasma sodium, potassium, creatinine, or any urinary measurements. CONCLUSION: beta-Blockers can significantly raise the ARR and thereby increase the risk of false positives during screening for PAL.