Synergistic inhibitory effect of angiotensin II receptor blocker and thiazide diuretic on the tissue renin-angiotensin-aldosterone system

Abstract

ARBs are conceptually more potent in a high renin state than in a low renin state at blood pressure reduction and cardiovascular protection, whereas the potency of thiazide diuretics in the contrary. However, the additive effect of the agents when used in combination remains unclear. Thus, the goal of the present review was to analyse available data to explain the mechanistic actions of the ARB-thiazide diuretic combination. Although the circulating renin-angiotensin-aldosterone system (RAAS) has been well characterised in the context of cardiovascular disease, recent attention has also focused on the role of the tissue RAAS. For example, both angiotensin II and aldosterone are produced in small amounts within cardiac tissue, and the angiotensin II type 1 receptor is widely distributed and activated within cardiovascular tissues. Recent reports also suggest that the mineralocorticoid receptor is activated through Rac1 GTP-ase in high salt-intake rats. Thus, many components of the RAAS are activated in cardiovascular tissues under high salt-intake conditions, and a low salt diet or use of diuretics likely suppresses the tissue RAAS. Since ARBs can block the effect of both tissue angiotensin II and circulating angiotensin II, it follows that the combination of an ARB and a thiazide diuretic results in synergistic inhibition of the tissue RAAS.