Angiotensin II Induces Interleukin-6 in Humans Through a Mineralocorticoid Receptor

This study tested the hypothesis that angiotensin promotes oxidative stress and inflammation in humans via aldosterone and the mineralocorticoid receptor. We measured the effect of intravenous aldosterone (0.7 g/kg per hour for 10 hours followed by 0.9 g/kg per hour for 4 hours) and vehicle in a randomized, double-blind crossover study in 11 sodium-restricted normotensive subjects. Aldosterone increased interleukin (IL)-6 (from 4.7 4.9 to 9.4 7.1 pg/mL; F 4.94; P 0.04) but did not affect blood pressure, serum potassium, or high-sensitivity C-reactive protein. We next conducted a randomized, double-blind, placebo-controlled, crossover study to measure the effect of 3-hour infusion of angiotensin II (2 ng/kg per minute) and norepinephrine (30 ng/kg per minute) on separate days after 2 weeks of placebo or spironolactone (50 mg per day) in 14 salt-replete normotensive subjects. Angiotensin II increased blood pressure (increase in systolic pressure: 13.7 7.5 and 15.2 9.4 mm Hg during placebo and spironolactone, respectively; P 0.001 for angiotensin II) and decreased renal plasma flow ( 202 73 and 167 112 mL/min/1.73 kg/m; P 0.001 for angiotensin II effect) similarly during placebo and spironolactone. Spironolactone enhanced the aldosterone response to angiotensin II (increase of 17.0 10.6 versus 9.0 5.7 ng/dL; P 0.002). Angiotensin II transiently increased free plasma F2-isoprostanes similarly during placebo and spironolactone. Angiotensin II increased serum IL-6 concentrations during placebo (from 1.8 1.1 to 2.4 1.4 pg/mL; F 4.5; P 0.04) but spironolactone prevented this effect (F 6.4; P 0.03 for spironolactone effect). Norepinephrine increased blood pressure and F2-isoprostanes but not aldosterone or IL-6. Aldosterone increases IL-6 in humans. These data suggest that angiotensin II induces IL-6 through a mineralocorticoid receptor–dependent mechanism in humans. In contrast, angiotensin II–induced oxidative stress, as measured by F2-isoprostanes, is mineralocorticoid receptor independent and may be pressor dependent. (Hypertension. 2006;48:1050-1057.)