Dual renin???angiotensin system blockade restores blood pressure???renin dependency in individuals with low renin concentrations

Background The prevailing sodium intake and renin–angiotensin system status influence the blood pressure response to an angiotensin II type 1 (AT1) receptor antagonist or an angiotensin I converting enzyme inhibitor, which is known to be reinforced by a low sodium intake or administration of a diuretic. Objective To investigate the possibility that combining both drugs might be more effective in conditions of high sodium intake than blocking the renin–angiotensin system in a single step. Methods In a placebo-controlled, four-period crossover study in 12 normotensive volunteers who received a high sodium chloride intake (more than 250 mmol/day for 6 days), the haemodynamic and renin effects of a single oral dose of irbesartan 150 mg combined with fosinopril 20 mg were compared with those of a usual daily dose of fosinopril (20 mg) and a high dose of irbesartan (300 mg). Results The changes in blood pressure induced by fosinopril and irbesartan alone were not different from those of placebo, whereas the combination significantly decreased blood pressure. Simultaneously, it increased plasma active renin and prorenin concentrations to a greater extent than did each single-site blocker. Conclusion In low-renin conditions, combined renin–angiotensin system blockade enables the demonstration of a persistent renin-dependency of the blood pressure. Through its more efficient blockade of the renin–angiotensin system, demonstrated by the increase in renin and prorenin, combined renin–angiotensin system blockade is more effective than doubling the usual dose of an AT1 receptor antagonist. This may offer an alternative strategy for treating patients with a range of renin concentrations, and may potentially increase the cardio- and nephrotective benefits through a more complete blockade of the renin–angiotensin system.