G protein-coupled receptor kinases in hypertension: physiology, pathogenesis, and therapeutic targets

Authors

Fuwei Zhang, Research Center for Metabolic and Cardiovascular Diseases, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.
Ines Armando, Division of Renal Diseases & Hypertension, Department of Medicine and Department of Physiology/Pharmacology, The George Washington University School of Medicine & Health Sciences, Washington, DC, USA.
Pedro A. Jose, Division of Renal Diseases & Hypertension, Department of Medicine and Department of Physiology/Pharmacology, The George Washington University School of Medicine & Health Sciences, Washington, DC, USA.
Chunyu Zeng, Department of Cardiology, Daping Hospital, The Third Military Medical University (Army Medical University), Chongqing, PR China.
Jian Yang, Research Center for Metabolic and Cardiovascular Diseases, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. jianyang@hospital.cqmu.edu.cn.

Document Type

Journal Article

Publication Date

9-1-2024

Journal

Hypertension research : official journal of the Japanese Society of Hypertension

Volume

47

Issue

9

DOI

10.1038/s41440-024-01763-y

Keywords

Blood pressure; G protein-coupled receptor; G protein-coupled receptor kinase; Hypertension

Abstract

G protein-coupled receptors (GPCRs) mediate cellular responses to a myriad of hormones and neurotransmitters that play vital roles in the regulation of physiological processes such as blood pressure. In organs such as the artery and kidney, hormones or neurotransmitters, such as angiotensin II (Ang II), dopamine, epinephrine, and norepinephrine exert their functions via their receptors, with the ultimate effect of keeping normal vascular reactivity, normal body sodium, and normal blood pressure. GPCR kinases (GRKs) exert their biological functions, by mediating the regulation of agonist-occupied GPCRs, non-GPCRs, or non-receptor substrates. In particular, increasing number of studies show that aberrant expression and activity of GRKs in the cardiovascular system and kidney inhibit or stimulate GPCRs (e.g., dopamine receptors, Ang II receptors, and α- and β-adrenergic receptors), resulting in hypertension. Current studies focus on the effect of selective GRK inhibitors in cardiovascular diseases, including hypertension. Moreover, genetic studies show that GRK gene variants are associated with essential hypertension, blood pressure response to antihypertensive medicines, and adverse cardiovascular outcomes of antihypertensive treatment. In this review, we present a comprehensive overview of GRK-mediated regulation of blood pressure, role of GRKs in the pathogenesis of hypertension, and highlight potential strategies for the treatment of hypertension. Schematic representation of GPCR desensitization process. Activation of GPCRs begins with the binding of an agonist to its corresponding receptor. Then G proteins activate downstream effectors that are mediated by various signaling pathways. GPCR signaling is halted by GRK-mediated receptor phosphorylation, which causes receptor internalization through β-arrestin.

APA Citation

Zhang, Fuwei; Armando, Ines; Jose, Pedro A.; Zeng, Chunyu; and Yang, Jian, "G protein-coupled receptor kinases in hypertension: physiology, pathogenesis, and therapeutic targets" (2024). GW Authored Works. Paper 5738.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5738

Department

Medicine