Renin-angiotensin system is involved in the mechanism of increased serum asymmetric dimethylarginine in essential hypertension.

Abstract

Endothelium-dependent/nitric oxide (NO)-mediated vasodilation is impaired in hypertensive individuals. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is synthesized by many types of cells including vascular endothelial cells. The serum level of ADMA is elevated in patients with essential hypertension, but the mechanism for this increase is unknown. Therefore, the present study examined whether the renin-angiotensin system (RAS) is involved. Patients with essential hypertension [systolic blood pressure (BP) > 160 mmHg and/or diastolic BP > 95 mmHg] were randomized to an angiotensin-converting enzyme (ACE) inhibitor treatment group (perindopril, 4mg/day for 4 weeks, n = 7), an angiotensin II type 1 (AT1) receptor antagonist treatment group (losartan, 50 mg/day for 4 weeks, n = 7) or a beta-blocker treatment group (bisoprolol, 5 mg/day for 4 weeks, n = 7). Before and after the treatment, BP, serum concentration of ADMA and plasma concentration of von Willebrand factor (vWF, a biological marker of endothelial injury) were measured. Perindopril, losartan and bisoprolol decreased BP to a similar extent, and either perindopril or losartan, but not bisoprolol, significantly decreased serum ADMA and plasma vWF. These findings suggest that the RAS may contribute to the mechanism of increased serum ADMA as well as to the endothelial injury observed in hypertensive patients. The vasculoprotective actions of ACE inhibitors or AT1 receptor antagonists may be explained at least in part by amelioration of the endothelial injury through a decrease in the serum ADMA concentration.