Coronary microvascular endothelial cell redox state in left ventricular hypertrophy - The role of angiotensin II

Left ventricular hypertrophy (LVH) is associated with elevated plasma angio tensin Il (Ang II) levels and endothelial dysfunction, The relationship bet ween Ang II and endothelial dysfunction remains unknown, however, but it ma y involve an alteration in endothelial cell redox state. We therefore inves tigated the effect of Ang II on NADH/NADPH oxidase-mediated superoxide anio n (O-2(-)) production by cultured guinea pig coronary microvascular endothe lial cells (CMVEs) and CMVEs freshly isolated from a guinea pig, pressure-o verload model of LVH. Lucigenin chemiluminescence was used to measure O-2(- ) production in the particulate fraction of CMVE lysates. In cultured cells , incubation with Ang II (0.1 nmol/L to 1 mu mol/L for 18 hours) resulted i n significant (P<0.01) increases in both NADH-and NADPH-dependent O-2(-) pr oduction, with a peak effect at 1 nmol/L. The latter was significantly (P<0 .01) inhibited by the AT, receptor antagonist losartan (1 mu mol/L for Is h ours). In contrast, the O-2(-) response to Ang II (0.1 nmol/L to 1 mu mol/L for 18 hours) was largely unaffected by concomitant exposure to the AT(2) antagonist PD 123319 (1 mu mol/L). In freshly isolated CMVEs from nonoperat ed animals, NADH- and NADPH-dependent O-2(-) production was not different f rom that in sham-operated animals but was significantly (P<0.05) elevated i n the aortic-banded animals. Plasma Ang II levels were significantly (P<0.0 01) elevated in the aortic-banded (1.25+/-0.12 mu g/L, n=12) compared with sham-operated animals (0.63+/-0.06 mu g/L, n=12). These data suggest that t he endothelial dysfunction associated with LVH may be due, at least in part , to the Ang II-induced upregulation of NADH/NADPH oxidase-dependent O-2(-) production.