High plasma level of asymmetric dimethylarginine in patients with acutely exacerbated congestive heart failure: role in reduction of plasma nitric oxide level

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is elevated in congestive heart failure (CHF) concomitantly with the higher levels of nitric oxide (NO) and cytokines. We investigated the association among ADMA, NO, and cytokines in human CHF. Blood was collected from 25 patients with acutely exacerbated chronic CHF (acute CHF, mean age 61 +/- 3 years), 23 patients with chronic compensated CHF (chronic CHF, mean age 62 +/- 2 years), and 26 control subjects (mean age 51 +/- 1 years). ADMA was measured by high-performance liquid chromatography. Tumor necrosis factor-alpha (TNF-alpha) was measured by enzyme-linked immunosorbent assay. Nitrate plus nitrite (NOx) was measured by the Griess method. The plasma levels of ADMA and TNF-Alpha were higher in patients with acute CHF than in those with chronic CHF and control subjects (both P < 0.05). The plasma level of NOx was higher in patients with chronic CHF than in those with acute CHF and control subjects (both P < 0.01). The plasma level of TNF-Alpha was positively correlated with that of ADMA in combination with patients with acute and chronic CHF (r = 0.31, P < 0.01). The plasma level of ADMA was, furthermore, negatively correlated with that of NOx (r = -0.29, P < 0.05). These findings indicate that ADMA is related to exacerbation of chronic CHF by suppression of the compensatory higher level of plasma NO.