REVIEW Small Vessels-Big Problems: Novel Insights into Microvascular Mechanisms of Diseases Antihypertensive effects of peroxisome proliferator-activated receptor- beta/delta activation

摘要

Toral M, Romero M, Perez-Vizcaino F, Duarte J, Jimenez R. Antihypertensive effects of peroxisome proliferator-activated receptor-beta/delta activation. Am J Physiol Heart Circ Physiol 312: H189-H200, 2017. First published November 23, 2016; doi:10.1152/ajpheart.00155.2016.Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors, which is composed of three members encoded by distinct genes: PPARalpha, PPARbeta/delta, and PPAR7. The biological actions of PPARalpha and PPARgamma and their potential as a cardiovascular therapeutic target have been extensively reviewed, whereas the biological actions of PPARbeta/delta and its effectiveness as a therapeutic target in the treatment of hypertension remain less investigated. Preclinical studies suggest that pharmacological PPAR beta/delta activation induces antihypertensive effects in direct [spontaneously hypertensive rat (SHR), ANG II, and DOCA-salt] and indirect (dyslipemic and gestational) models of hypertension, associated with end-organ damage protection. This review summarizes mechanistic insights into the antihypertensive effects of PPAR beta/delta activators, including molecular and functional mechanisms. Pharmacological PPAR beta/delta activation induces genomic actions including the increase of regulators of G protein-coupled signaling (RGS), acute nongenomic vasodilator effects, as well as the ability to improve the endothelial dysfunction, reduce vascular inflammation, vasoconstrictor responses, and sympathetic outflow from central nervous system. Evidence from clinical trials is also examined. These preclinical and clinical outcomes of PPAR beta/delta ligands may provide a basis for the development of therapies in combating hypertension.