Coronary Microvascular Endothelial Cell Redox State in Left Ventricular Hypertrophy

Abstract

—Left ventricular hypertrophy (LVH) is associated with elevated plasma angiotensin II (Ang II) levels and endothelial dysfunction. The relationship between Ang II and endothelial dysfunction remains unknown, however, but it may involve an alteration in endothelial cell redox state. We therefore investigated the effect of Ang II on NADH/NADPH oxidase–mediated superoxide anion (O₂⁻) production by cultured guinea pig coronary microvascular endothelial cells (CMVEs) and CMVEs freshly isolated from a guinea pig, pressure-overload model of LVH. Lucigenin chemiluminescence was used to measure O₂⁻ production in the particulate fraction of CMVE lysates. In cultured cells, incubation with Ang II (0.1 nmol/L to 1 μmol/L for 18 hours) resulted in significant (P2⁻ production, with a peak effect at 1 nmol/L. The latter was significantly (P1 receptor antagonist losartan (1 μmol/L for 18 hours). In contrast, the O₂⁻ response to Ang II (0.1 nmol/L to 1 μmol/L for 18 hours) was largely unaffected by concomitant exposure to the AT₂ antagonist PD 123319 (1 μmol/L). In freshly isolated CMVEs from nonoperated animals, NADH- and NADPH-dependent O₂⁻ production was not different from that in sham-operated animals but was significantly (PP2⁻ production.