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

Abstract

Lu X, Dang CQ, Guo X, Molloi S, Wassall CD, Kemple MD, Kassab GS. Elevated oxidative stress and endothelial dysfunction in right coronary artery of right ventricular hypertrophy. J Appl Physiol 110: 1674 -1681, 2011. First published March 17, 2011 doi:10.1152/japplphysiol.00744.2009.-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 ϭ 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 ϳ100% 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.remodeling; endothelial nitric oxide synthase uncoupling; reactive oxygen species RIGHT VENTRICULAR HYPERTROPHY (RVH) results in significant remodeling of right coronary artery (RCA) (3-7, 10, 12). The morphometric data of RCA main trunk, arterioles, and capillaries in RVH suggest outward remodeling in main trunk and increase in numbers of resistance and capillary vessels (12). A hemodynamic analysis showed RCA compensatory adaption during RVH to restore the perfusion at the arteriolar and capillary levels and increase blood flow in the main trunk (10), in proportion to increase in right ventricle (RV) mass (12). The effect of RVH on RCA endothelial function, however, remains unclear.Endothelial function plays an important role in vascular pathophysiology and is a biomarker/mediator of cardiovascular risk factors (2,4,5,12,16,21,24). Endothelial dysfunction has also been shown to be a predictor of adverse outcomes in patients with coronary artery disease (11,12). Nitric oxide (NO) is well known as endothelium-dependent vasodilator and is believed to play an atheroprotective role. Reactive oxygen species (ROS) are free radicals found in all vascular cells that are involved in remodeling in both physiological and pathological conditions (1, 4 -8). ROS can inactivate NO and decrease NO bioavailability in blood vessels that may compromise endothelium-dependent...

Scalability and in vivo validation of a multiscale numerical model of the left coronary circulation

“…That these effects play a role in shaping the coronary arterial flow waveform was first suggested by Rumberger et al (54,55) on the basis of flow transients ("oscillations") observed in early systole and diastole in the left anterior descending artery of horses, features that are also evident in published waveforms from humans and other species (5,14,38,76). More recently, therefore, a number of one-dimensional (1D) or multiscale (i.e., combined 0D/1D) models of the coronary circulation, which are best suited to the study of wave propagation effects, have been described (25,45,52,57,58,71).…”

Protective effects of Astragalus polysaccharides against endothelial dysfunction in hypertrophic rats induced by isoproterenol

“…It has been recognized as an independent predictor to a variety of cardiovascular diseases such as hypertension [1], diabetes [2], atherosclerosis [3], chronic kidney disease [4], as well as in general population [5]. It has been reported that endothelial dysfunction of conduit or resistance arteries is often concurrent with myocardial hypertrophy in hypertensive model rats [6][7][8], angiotensin II-infused model rats [9] and model of swines with aortic banding [10]. The association between cardiac hypertrophy and impaired endothelial function has also been reported in humans of chronic kidney disease [11], atherosclerosis [3] and nevertreated hypertensive patients [12].…”

Involvement of NADPH oxidase in A2A adenosine receptor-mediated increase in coronary flow in isolated mouse hearts

“…These findings further support NADPH oxidase as a functionally relevant source of ROS for regulating coronary vascular tone. As both adenosine and ROS are generated and released under pathophysiological conditions [9,65] and generated ROS mainly exerts a detrimental influence on the coronary vasculature [54][55][56], future studies addressing the role of A 2A AR in ROS-mediated coronary vascular tone regulation in pathophysiological conditions will bring us greater insights into mechanisms underlying ischemic heart disease.…”

“…This heterogeneity might be due to vasoconstrictor ROS vs. vasodilator ROS [29,31] generated from different vascular beds (coronary vs. renal artery) [34,37]. Furthermore, in the coronary vasculature, the varying effects of ROS may depend on which source ROS are generated from (NADPH vs. uncoupled NO synthase) [31,52,53] or the pathophysiological conditions [32,52,53], e.g., diabetes, and the right ventricular hypertrophy [54][55][56]. In accordance with our previous studies [37], the effect of ROS scavenging with EUK134 was comparable with the effect of Nox2 inhibition with gp91 ds-tat in WT isolated hearts (P=0.24), suggesting that the majority of ROS generated by adenosine is likely from Nox2, which leads to increases in coronary flow.…”