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: PPARα, PPARβ/δ, and PPARγ. The biological actions of PPARα and PPARγ and their potential as a cardiovascular therapeutic target have been extensively reviewed, whereas the biological actions of PPARβ/δ and its effectiveness as a therapeutic target in the treatment of hypertension remain less investigated. Preclinical studies suggest that pharmacological PPARβ/δ activation induces antihypertensive effects in direct (SHR, AngII, DOCA-salt) and indirect (dyslipemic, gestational) models of hypertension, associated with end-organ damage protection. This review summarizes mechanistic insights into the antihypertensive effects of PPARβ/δ activators, including molecular and functional mechanisms. Pharmacological PPARβ/δ activation induces genomic actions including the increase of regulators of G-protein-coupled signaling (RGS), acute non-genomic vasodilator effects, as well as their ability to improve the endothelial dysfunction, reduce vascular inflammation, vasoconstrictor responses and sympathetic outflow from central nervous system. Evidences from clinical trials are also examined. These pre-clinical and clinical outcomes of PPARβ/δ ligands may provide a basis for the development of therapies in combating hypertension.
- endothelial dysfunction
- vascular remodeling
- oxidative stress
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology