Increased nitric oxide activity by converting enzyme inhibition improves endothetial dysfunction in humans

Angiotensin converting enzyme inhibitors (ACEI) have vasculoprotective effects. We hypothesized that this is due to their ability to reduce bradylunin (BK) degradation and thus increase nitric oxide activity. In the femoral circulation of 45 pts, 41 of whom had atherosclerosis or its risk factors, we studied endothelium-dependent vasodilation with BK (250 ng/min) and acetylcholine (ACh, 300 μg/min), and endothelium-independent vasodilation with sodium nitroprusside (SNP, 40 μg/min) before and after enalaprilat (EN, 20 μg/min). In 16 pts, we repeated the infusions in the presence of L-N^G monomethyl arginine (L-NMMA, 64μmol/min), an inhibitor of nitric oxide synthase. Femoral artery flow velocity was measured using a Doppler flow wire and the resistance index (RI= mmHg·cm^-1·sec) calculated as mean arterial pressure ÷flow velocity. EN did not alter resting RI (5.8±1.8, mean±SD) but enhanced BK mediated dilation (2.7±1.0 to 2.0±0.7 RI, p<0.001). The potentiation of ACh mediated dilation with EN was inversely proportional to the baseline ACh response (r= -0.5, p<0.005). EN did not potentiate SNP mediated vasodilation. L-NMMA inhibited the effect of BK (p<0.07) and ACh (p=0.02), but not SNP (p=0.7). Furthermore, in the presence of L-NMMA, EN did not potentiate BK (3.1±1.1 to 3.6±1.4 RI) and ACh (5.3±2.6 to 5.4±3.1 RI) responses. These findings suggest that ACEI selectively improve endothelium-dependent vascular function in patients, particularly those with endothelial dysfunction. Increased nitric oxide activity with ACEI is in part responsible for this beneficial effect.