Antihypertensive effects of peroxisome proliferator-activated receptor-β/δ activation.

Abstract

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 [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 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 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 PPARβ/δ ligands may provide a basis for the development of therapies in combating hypertension.

• Authors: Marta Toral, Miguel Romero, Francisco Pérez-Vizcaíno, Juan Duarte, Rosario Jiménez
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 312 Issue 2 Pg. H189-H200 (Feb 01 2017) ISSN: 1522-1539 [Electronic] United States
• PMID: 27881385 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2017 the American Physiological Society.

Chemical References

• 4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid
• Antihypertensive Agents
• Fatty Acids
• GW 501516
• PPAR delta
• PPAR-beta
• Phenoxyacetates
• RGS Proteins
• Thiazoles
• (4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid

Topics

• Animals
• Antihypertensive Agents (pharmacology, therapeutic use)
• Blood Pressure (drug effects, physiology)
• Endothelium, Vascular (physiopathology)
• Fatty Acids (metabolism)
• Gene Expression Regulation
• Humans
• Hypertension (drug therapy, physiopathology)
• Inflammation
• PPAR delta (agonists, metabolism, physiology)
• PPAR-beta (agonists, metabolism, physiology)
• Phenoxyacetates (pharmacology, therapeutic use)
• RGS Proteins (drug effects, genetics)
• Rats
• Rats, Inbred SHR
• Sympathetic Nervous System (physiopathology)
• Thiazoles (pharmacology, therapeutic use)
• Vasoconstriction (drug effects, physiology)
• Vasodilation (drug effects, physiology)