Nitric oxide and coronary vascular endothelium adaptations in hypertension

Abstract

This review highlights a number of nitric oxide (NO)-related mechanisms that contribute to coronary vascular function and that are likely affected by hypertension and thus become important clinically as potential considerations in prevention, diagnosis, and treatment of coronary complications of hypertension. Coronary vascular resistance is elevated in hypertension in part due to impaired endothelium-dependent function of coronary arteries. Several lines of evidence suggest that other NO synthase isoforms and dilators other than NO may compensate for impairments in endothelial NO synthase (eNOS) to protect coronary artery function, and that NO-dependent function of coronary blood vessels depends on the position of the vessel in the vascular tree. Adaptations in NOS isoforms in the coronary circulation to hypertension are not well described so the compensatory relationship between these and eNOS in hypertensive vessels is not clear. It is important to understand potential functional consequences of these adaptations as they will impact the efficacy of treatments designed to control hypertension and coronary vascular disease. Polymorphisms of the eNOS gene result in significant associations with incidence of hypertension, although mechanistic details linking the polymorphisms with alterations in coronary vasomotor responses and adaptations to hypertension are not established. This understanding should be developed in order to better predict those individuals at the highest risk for coronary vascular complications of hypertension. Greater endothelium-dependent dilation observed in female coronary arteries is likely related to endothelial Ca 2+ control and eNOS expression and activity. In hypertension models, the coronary vasculature has not been studied extensively to establish mechanisms for sex differences in NO-dependent function. Genomic and nongenomic effects of estrogen on eNOS and direct and indirect antioxidant activities of estrogen are discussed as potential mechanisms of interest in coronary circulation that could have implications for sex-and estrogen status-dependent therapy for hypertension and coronary dysfunction. The current review identifies some important basic knowledge gaps and speculates on the potential clinical relevance of hypertension adaptations in factors regulating coronary NO function.

Role of Exogenous Nitric Oxide Donor in Treatment of Decompensated Hemorrhagic Shock in Normotensive and Hypertensive Rats

“…Previous studies also supported the lower NO bioavailability in hypertensive subjects [ 15 – 17 ]. Higher production of reactive oxygen species, lower endothelial NO synthase expression, and/or impaired L-arginine uptake are possible mechanisms for reduced NO bioavailability in hypertensive subjects [ 16 , 17 ].…”

“…[ 18 ] Reduced NO bioavailability in hypertensive subjects has been documented in previous studies,[ 10 23 24 ] and different mechanisms have been suggested for reduced availability of NO during hypertension, including the generation of reactive oxygen species, impaired l-arginine uptake,[ 23 ] or reduced NOS expression. [ 24 ]…”

“…In this study, we found that serum NO concentration in hypertensive animals was lower than normotensive group. Hypertension is associated with cardiovascular abnormalities including endothelial dysfunction and it seems that reduced serum NO concentration in hypertensive group may be the result of endothelial dysfunction [ 16 , 17 ]. Previous studies also supported the lower NO bioavailability in hypertensive subjects [ 15 – 17 ].…”

“…Hypertension is associated with cardiovascular abnormalities including endothelial dysfunction and it seems that reduced serum NO concentration in hypertensive group may be the result of endothelial dysfunction [ 16 , 17 ]. Previous studies also supported the lower NO bioavailability in hypertensive subjects [ 15 – 17 ]. Higher production of reactive oxygen species, lower endothelial NO synthase expression, and/or impaired L-arginine uptake are possible mechanisms for reduced NO bioavailability in hypertensive subjects [ 16 , 17 ].…”

Analysis of Oxidative Stress Enzymes and Structural and Functional Proteins on Human Aortic Tissue from Different Aortopathies

“…In the pathologies studied, the presence of aneurisms contributes to endothelial dysfunction and the increase in the NO 3 − and NO 2 − ratio can favor the increase of peroxynitrites. In addition, altered NO bioavailability contributes to the modified vasomotion in hypertension [ 95 ] where an increased production of ROS is associated with an elevated production of peroxynitrite in coronary blood vessels. Endothelial dysfunction also promotes an increase in the generation of O 2 − leading to an enhanced NO inactivation against peroxynitrites [ 93 ].…”