Elevated oxidative stress and endothelial dysfunction in right coronary artery of right ventricular hypertrophy

Abstract

Remodeling of right coronary artery (RCA) occurs during right ventricular hypertrophy (RVH) induced by banding of the pulmonary artery (PA). The effect of RVH on RCA endothelial function and reactive oxygen species (ROS) in vessel wall remains unclear. A swine RVH model (n = 12 pigs) induced by PA banding was used to study RCA endothelial function and ROS level. To obtain longitudinal coronary hemodynamic and geometric data, digital subtraction angiography was used during the progression of RVH. Blood flow in the RCA increased by 82% and lumen diameter of RCA increased by 22% over a 4-wk period of RVH. The increase in blood flow and the commensurate increase in diameter resulted in a constant wall shear stress in RCA throughout the RVH period. ROS was elevated by ∼100% in RCA after 4 wk of PA banding. The expressions of p47(phox), NADPH oxidase (NOX1, NOX2, and NOX4) were upregulated in the range of 20-300% in RCA of RVH. The endothelial function was compromised in RCA of RVH as attributed to insufficient endothelial nitric oxide synthase cofactor tetrahydrobiopterin. In vivo angiographic analysis suggests an increased basal tone in the RCA during RVH. In conclusion, stretch due to outward remodeling of RCA during RVH (at constant wall shear stress), similar to vessel stretch in hypertension, appears to induce ROS elevation, endothelial dysfunction, and an increase in basal tone.