Redox signaling, vascular function, and hypertension

Abstract

Accumulating evidence supports the importance of redox signaling in the pathogenesis and progression of hypertension. Redox signaling is implicated in many different physiological and pathological processes in the vasculature. High blood pressure is in part determined by elevated total peripheral vascular resistance, which is ascribed to dysregulation of vasomotor function and structural remodeling of blood vessels. Aberrant redox signaling, usually induced by excessive production of reactive oxygen species (ROS) and/or by decreases in antioxidant activity, can induce alteration of vascular function. ROS increase vascular tone by influencing the regulatory role of endothelium and by direct effects on the contractility of vascular smooth muscle. ROS contribute to vascular remodeling by influencing phenotype modulation of vascular smooth muscle cells, aberrant growth and death of vascular cells, cell migration, and extracellular matrix (ECM) reorganization. Thus, there are diverse roles of the vascular redox system in hypertension, suggesting that the complexity of redox signaling in distinct spatial spectrums should be considered for a better understanding of hypertension.

FIG. 1

Regulation of endothelium-dependent vasodilation by ROS. Superoxide not only inactivates NO, but also inhibits prostacyclin, decreases guanylate cyclase expression, and blocks K_ATP and K_v channels. In contrast, H₂O₂ opens these channels. By interacting with NO to form peroxynitrite, superoxide also oxidizes the eNOS cofactor tetrahydrobiopterin and inhibits K_Ca and K_v channels.

FIG. 2

ROS-mediated contribution of vascular smooth muscle cells to vascular remodeling in hypertension. Phenotypic modulation of vascular smooth muscle is central to the development of remodeling in hypertension. ECM, extracellular matrix; MMPs, matrix metalloproteinases.