Sodium status and angiotensin-converting enzyme inhibition: effects on plasma angiotensin-(1-7) in healthy man

Objective Angiotensin-converting enzyme (ACE) inhibitors provide effective intervention for cardiovascular and renal disease. Changes in angiotensin-(1-7) have been proposed to be involved in the mechanism of action of ACE inhibition (ACEi). In particular, an altered balance between angiotensin II and angiotensin-(1-7) might be involved. A shift in sodium status modifies the activity of the renin-angiotensin-aldosterone system and the effects of ACEi, but its effects on angiotensin(1-7) are unknown. We therefore studied the effect of a shift in sodium intake on angiotensin-(1-7), during placebo and ACEi. Methods A double-blind, placebo-controlled study was conducted in 17 healthy men. The subjects were studied for two 2-week periods: 20 mg/day enalapril and placebo. The first week of each period they used a 50 mmol Na+ diet [low sodium (LS)], the second week a 200 mmol Na+ diet. Angiotensin levels and blood pressure were measured at the end of each week. Results During placebo, LS intake elicited a three-fold rise in ang-(1-7) that paralleled the rise in other components of the renin-angiotensin system. During ACEi LS did not affect angiotensin II, but did induce a clear-cut rise in angiotensin-(1-7) - to the extent that angiotensin-(1-7)was highest during combination of ACEi and LS. Consequently, during ACE LS shifted the balance between angiotensin-(1-7) and angiotensin II towards angiotensin-(1-7). Conclusion The sodium status modifies levels of angiotensin-(1-7). During ACE angiotensin(1-7) is still subject to stimulation by sodium restriction, and provides opportunity for therapeutic manipulation. Exploration of this opportunity in patient populations may lead to strategies to improve therapeutic benefits of ACEL (c) 2005 Lippincott Williams & Wilkins.