ArticleHypertension (Dallas, Tex. : 1979)2016
Human GRK4γ142V Variant Promotes Angiotensin II Type I Receptor-Mediated Hypertension via Renal Histone Deacetylase Type 1 Inhibition.
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Article in Hypertension (Dallas, Tex. : 1979), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33citing papers in PubMed
1.6field-weighted citation impact, top 15% of its field
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Who cites it
33 citing papers in PubMed, 39 citations in OpenAlex.
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- Role of G-protein-coupled receptor kinase 4 on the dysfunction of renal Mas receptor in hypertension.PloS one · 2025Article
- Podocyte cell-specificPhysiological genomics · 2024Article
- G protein-coupled receptor kinases in hypertension: physiology, pathogenesis, and therapeutic targets.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- Epigenetic mechanisms differentially regulate blood pressure and renal dysfunction in male and female Npr1 haplotype mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Novel roles for G protein-coupled receptor kinases in cardiac injury and repair.Biochemical Society transactions · 2023Review
- Downregulation of G protein-coupled receptor kinase 4 protects against kidney ischemia-reperfusion injury.Kidney international · 2023Article
- Dopamine Receptor DThe Yale journal of biology and medicine · 2023Review
- Inverse Salt Sensitivity of Blood Pressure Is Associated with an Increased Renin-Angiotensin System Activity.Biomedicines · 2022Article
- Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics.Pharmacology & therapeutics · 2022Review
- Inverse Salt Sensitivity of Blood Pressure: Mechanisms and Potential Relevance for Prevention of Cardiovascular Disease.Current hypertension reports · 2022Review
- Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal NaHypertension (Dallas, Tex. : 1979) · 2022Article
- G-protein-coupled receptor kinase 4 causes renal angiotensin II type 2 receptor dysfunction by increasing its phosphorylation.Clinical science (London, England : 1979) · 2022Article
- Paternal long-term PM2.5 exposure causes hypertension via increased renal AT1R expression and function in male offspring.Clinical science (London, England : 1979) · 2021Article
- Genetic variants of GRK4 influence circadian rhythm of blood pressure and response to candesartan in hypertensive patients.Clinical and experimental hypertension (New York, N.Y. : 1993) · 2021Article
- Increased ATHypertension research : official journal of the Japanese Society of Hypertension · 2021Article
- The role of G protein-coupled receptor kinase 4 in cardiomyocyte injury after myocardial infarction.European heart journal · 2021Article
- Transplantation of Apoptosis-Resistant Endothelial Progenitor Cells Improves Renal Function in Diabetic Kidney Disease.Journal of the American Heart Association · 2021Article
- The Role of the Renal Dopaminergic System and Oxidative Stress in the Pathogenesis of Hypertension.Biomedicines · 2021Review
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Authors and funding
15 authors at 6 institutions in 2 countries.
Zheng WangFrom the Division of Pediatric Nephrology, Department of Pediatrics, Georgetown University of School of Medicine, Washington, DC (Z.W.); Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China (C.Z.); Chongqing Institute of Cardiology, Chongqing, P.R. China; Division of Nephrology, Department of Medicine (V.A.M.V., X.W., L.D.A., J.E.J., Y.Y., M.R.W., I.A., P.A.J.) and Department of Physiology (P.A.J.), University of Maryland School of Medicine, Baltimore, MD; Department of Physiology and Pharmacology, University of Georgia, Athens, GA (S.-Y.C.); Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan (H.S.); Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville (R.A.F.); Department of Medicine, Georgetown University Medical Center, Washington, DC (G.M.E.); Division of Renal Diseases and Hypertension, Department of Medicine (P.A.J.) and Department of Physiology (P.A.J.), The George Washington University School of Medicine and Health Sciences, Washington, DC.
Chunyu ZengFrom the Division of Pediatric Nephrology, Department of Pediatrics, Georgetown University of School of Medicine, Washington, DC (Z.W.); Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China (C.Z.); Chongqing Institute of Cardiology, Chongqing, P.R. China; Division of Nephrology, Department of Medicine (V.A.M.V., X.W., L.D.A., J.E.J., Y.Y., M.R.W., I.A., P.A.J.) and Department of Physiology (P.A.J.), University of Maryland School of Medicine, Baltimore, MD; Department of Physiology and Pharmacology, University of Georgia, Athens, GA (S.-Y.C.); Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan (H.S.); Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville (R.A.F.); Department of Medicine, Georgetown University Medical Center, Washington, DC (G.M.E.); Division of Renal Diseases and Hypertension, Department of Medicine (P.A.J.) and Department of Physiology (P.A.J.), The George Washington University School of Medicine and Health Sciences, Washington, DC.
Van Anthony M VillarFrom the Division of Pediatric Nephrology, Department of Pediatrics, Georgetown University of School of Medicine, Washington, DC (Z.W.); Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China (C.Z.); Chongqing Institute of Cardiology, Chongqing, P.R. China; Division of Nephrology, Department of Medicine (V.A.M.V., X.W., L.D.A., J.E.J., Y.Y., M.R.W., I.A., P.A.J.) and Department of Physiology (P.A.J.), University of Maryland School of Medicine, Baltimore, MD; Department of Physiology and Pharmacology, University of Georgia, Athens, GA (S.-Y.C.); Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan (H.S.); Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville (R.A.F.); Department of Medicine, Georgetown University Medical Center, Washington, DC (G.M.E.); Division of Renal Diseases and Hypertension, Department of Medicine (P.A.J.) and Department of Physiology (P.A.J.), The George Washington University School of Medicine and Health Sciences, Washington, DC.
Shi-You ChenFrom the Division of Pediatric Nephrology, Department of Pediatrics, Georgetown University of School of Medicine, Washington, DC (Z.W.); Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China (C.Z.); Chongqing Institute of Cardiology, Chongqing, P.R. China; Division of Nephrology, Department of Medicine (V.A.M.V., X.W., L.D.A., J.E.J., Y.Y., M.R.W., I.A., P.A.J.) and Department of Physiology (P.A.J.), University of Maryland School of Medicine, Baltimore, MD; Department of Physiology and Pharmacology, University of Georgia, Athens, GA (S.-Y.C.); Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan (H.S.); Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville (R.A.F.); Department of Medicine, Georgetown University Medical Center, Washington, DC (G.M.E.); Division of Renal Diseases and Hypertension, Department of Medicine (P.A.J.) and Department of Physiology (P.A.J.), The George Washington University School of Medicine and Health Sciences, Washington, DC.
Prasad KonkalmattFrom the Division of Pediatric Nephrology, Department of Pediatrics, Georgetown University of School of Medicine, Washington, DC (Z.W.); Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China (C.Z.); Chongqing Institute of Cardiology, Chongqing, P.R. China; Division of Nephrology, Department of Medicine (V.A.M.V., X.W., L.D.A., J.E.J., Y.Y., M.R.W., I.A., P.A.J.) and Department of Physiology (P.A.J.), University of Maryland School of Medicine, Baltimore, MD; Department of Physiology and Pharmacology, University of Georgia, Athens, GA (S.-Y.C.); Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan (H.S.); Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville (R.A.F.); Department of Medicine, Georgetown University Medical Center, Washington, DC (G.M.E.); Division of Renal Diseases and Hypertension, Department of Medicine (P.A.J.) and Department of Physiology (P.A.J.), The George Washington University School of Medicine and Health Sciences, Washington, DC.
Xiaoyan WangFrom the Division of Pediatric Nephrology, Department of Pediatrics, Georgetown University of School of Medicine, Washington, DC (Z.W.); Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China (C.Z.); Chongqing Institute of Cardiology, Chongqing, P.R. China; Division of Nephrology, Department of Medicine (V.A.M.V., X.W., L.D.A., J.E.J., Y.Y., M.R.W., I.A., P.A.J.) and Department of Physiology (P.A.J.), University of Maryland School of Medicine, Baltimore, MD; Department of Physiology and Pharmacology, University of Georgia, Athens, GA (S.-Y.C.); Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan (H.S.); Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville (R.A.F.); Department of Medicine, Georgetown University Medical Center, Washington, DC (G.M.E.); Division of Renal Diseases and Hypertension, Department of Medicine (P.A.J.) and Department of Physiology (P.A.J.), The George Washington University School of Medicine and Health Sciences, Washington, DC.
Laureano D AsicoFrom the Division of Pediatric Nephrology, Department of Pediatrics, Georgetown University of School of Medicine, Washington, DC (Z.W.); Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China (C.Z.); Chongqing Institute of Cardiology, Chongqing, P.R. China; Division of Nephrology, Department of Medicine (V.A.M.V., X.W., L.D.A., J.E.J., Y.Y., M.R.W., I.A., P.A.J.) and Department of Physiology (P.A.J.), University of Maryland School of Medicine, Baltimore, MD; Department of Physiology and Pharmacology, University of Georgia, Athens, GA (S.-Y.C.); Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan (H.S.); Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville (R.A.F.); Department of Medicine, Georgetown University Medical Center, Washington, DC (G.M.E.); Division of Renal Diseases and Hypertension, Department of Medicine (P.A.J.) and Department of Physiology (P.A.J.), The George Washington University School of Medicine and Health Sciences, Washington, DC.
John E JonesFrom the Division of Pediatric Nephrology, Department of Pediatrics, Georgetown University of School of Medicine, Washington, DC (Z.W.); Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China (C.Z.); Chongqing Institute of Cardiology, Chongqing, P.R. China; Division of Nephrology, Department of Medicine (V.A.M.V., X.W., L.D.A., J.E.J., Y.Y., M.R.W., I.A., P.A.J.) and Department of Physiology (P.A.J.), University of Maryland School of Medicine, Baltimore, MD; Department of Physiology and Pharmacology, University of Georgia, Athens, GA (S.-Y.C.); Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan (H.S.); Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville (R.A.F.); Department of Medicine, Georgetown University Medical Center, Washington, DC (G.M.E.); Division of Renal Diseases and Hypertension, Department of Medicine (P.A.J.) and Department of Physiology (P.A.J.), The George Washington University School of Medicine and Health Sciences, Washington, DC.
Yu YangFrom the Division of Pediatric Nephrology, Department of Pediatrics, Georgetown University of School of Medicine, Washington, DC (Z.W.); Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China (C.Z.); Chongqing Institute of Cardiology, Chongqing, P.R. China; Division of Nephrology, Department of Medicine (V.A.M.V., X.W., L.D.A., J.E.J., Y.Y., M.R.W., I.A., P.A.J.) and Department of Physiology (P.A.J.), University of Maryland School of Medicine, Baltimore, MD; Department of Physiology and Pharmacology, University of Georgia, Athens, GA (S.-Y.C.); Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan (H.S.); Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville (R.A.F.); Department of Medicine, Georgetown University Medical Center, Washington, DC (G.M.E.); Division of Renal Diseases and Hypertension, Department of Medicine (P.A.J.) and Department of Physiology (P.A.J.), The George Washington University School of Medicine and Health Sciences, Washington, DC.
Hironobu SanadaFrom the Division of Pediatric Nephrology, Department of Pediatrics, Georgetown University of School of Medicine, Washington, DC (Z.W.); Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China (C.Z.); Chongqing Institute of Cardiology, Chongqing, P.R. China; Division of Nephrology, Department of Medicine (V.A.M.V., X.W., L.D.A., J.E.J., Y.Y., M.R.W., I.A., P.A.J.) and Department of Physiology (P.A.J.), University of Maryland School of Medicine, Baltimore, MD; Department of Physiology and Pharmacology, University of Georgia, Athens, GA (S.-Y.C.); Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan (H.S.); Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville (R.A.F.); Department of Medicine, Georgetown University Medical Center, Washington, DC (G.M.E.); Division of Renal Diseases and Hypertension, Department of Medicine (P.A.J.) and Department of Physiology (P.A.J.), The George Washington University School of Medicine and Health Sciences, Washington, DC.
Robin A FelderFrom the Division of Pediatric Nephrology, Department of Pediatrics, Georgetown University of School of Medicine, Washington, DC (Z.W.); Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China (C.Z.); Chongqing Institute of Cardiology, Chongqing, P.R. China; Division of Nephrology, Department of Medicine (V.A.M.V., X.W., L.D.A., J.E.J., Y.Y., M.R.W., I.A., P.A.J.) and Department of Physiology (P.A.J.), University of Maryland School of Medicine, Baltimore, MD; Department of Physiology and Pharmacology, University of Georgia, Athens, GA (S.-Y.C.); Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan (H.S.); Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville (R.A.F.); Department of Medicine, Georgetown University Medical Center, Washington, DC (G.M.E.); Division of Renal Diseases and Hypertension, Department of Medicine (P.A.J.) and Department of Physiology (P.A.J.), The George Washington University School of Medicine and Health Sciences, Washington, DC.
Gilbert M EisnerFrom the Division of Pediatric Nephrology, Department of Pediatrics, Georgetown University of School of Medicine, Washington, DC (Z.W.); Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China (C.Z.); Chongqing Institute of Cardiology, Chongqing, P.R. China; Division of Nephrology, Department of Medicine (V.A.M.V., X.W., L.D.A., J.E.J., Y.Y., M.R.W., I.A., P.A.J.) and Department of Physiology (P.A.J.), University of Maryland School of Medicine, Baltimore, MD; Department of Physiology and Pharmacology, University of Georgia, Athens, GA (S.-Y.C.); Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan (H.S.); Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville (R.A.F.); Department of Medicine, Georgetown University Medical Center, Washington, DC (G.M.E.); Division of Renal Diseases and Hypertension, Department of Medicine (P.A.J.) and Department of Physiology (P.A.J.), The George Washington University School of Medicine and Health Sciences, Washington, DC.
Matthew R WeirFrom the Division of Pediatric Nephrology, Department of Pediatrics, Georgetown University of School of Medicine, Washington, DC (Z.W.); Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China (C.Z.); Chongqing Institute of Cardiology, Chongqing, P.R. China; Division of Nephrology, Department of Medicine (V.A.M.V., X.W., L.D.A., J.E.J., Y.Y., M.R.W., I.A., P.A.J.) and Department of Physiology (P.A.J.), University of Maryland School of Medicine, Baltimore, MD; Department of Physiology and Pharmacology, University of Georgia, Athens, GA (S.-Y.C.); Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan (H.S.); Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville (R.A.F.); Department of Medicine, Georgetown University Medical Center, Washington, DC (G.M.E.); Division of Renal Diseases and Hypertension, Department of Medicine (P.A.J.) and Department of Physiology (P.A.J.), The George Washington University School of Medicine and Health Sciences, Washington, DC.
Ines ArmandoFrom the Division of Pediatric Nephrology, Department of Pediatrics, Georgetown University of School of Medicine, Washington, DC (Z.W.); Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China (C.Z.); Chongqing Institute of Cardiology, Chongqing, P.R. China; Division of Nephrology, Department of Medicine (V.A.M.V., X.W., L.D.A., J.E.J., Y.Y., M.R.W., I.A., P.A.J.) and Department of Physiology (P.A.J.), University of Maryland School of Medicine, Baltimore, MD; Department of Physiology and Pharmacology, University of Georgia, Athens, GA (S.-Y.C.); Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan (H.S.); Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville (R.A.F.); Department of Medicine, Georgetown University Medical Center, Washington, DC (G.M.E.); Division of Renal Diseases and Hypertension, Department of Medicine (P.A.J.) and Department of Physiology (P.A.J.), The George Washington University School of Medicine and Health Sciences, Washington, DC.
Pedro A JoseFrom the Division of Pediatric Nephrology, Department of Pediatrics, Georgetown University of School of Medicine, Washington, DC (Z.W.); Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China (C.Z.); Chongqing Institute of Cardiology, Chongqing, P.R. China; Division of Nephrology, Department of Medicine (V.A.M.V., X.W., L.D.A., J.E.J., Y.Y., M.R.W., I.A., P.A.J.) and Department of Physiology (P.A.J.), University of Maryland School of Medicine, Baltimore, MD; Department of Physiology and Pharmacology, University of Georgia, Athens, GA (S.-Y.C.); Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan (H.S.); Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville (R.A.F.); Department of Medicine, Georgetown University Medical Center, Washington, DC (G.M.E.); Division of Renal Diseases and Hypertension, Department of Medicine (P.A.J.) and Department of Physiology (P.A.J.), The George Washington University School of Medicine and Health Sciences, Washington, DC. pjose@mfa.gwu.edu.
Georgetown University · USGeorgetown University Medical Center · USUniversity of Virginia · USArmy Medical University · CNDaping Hospital · CNUniversity of Georgia · US
Funding
Spatiotemporal transregulation of D1-like angiotensin receptors in genetically...P01HL074940 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI CAREY, ROBERT MUNSON · 2004 to 2020
$31.8MRenal Vascular Oxidative Stress in HypertensionP01HL068686 · NHLBI · GEORGETOWN UNIVERSITY · PI JOSE, PEDRO A., SANDBERG, KATHRYN L · 2001 to 2017
$28.8MRENAL DOPAMINE-1 RECEPTOR DEFECT IN HYPERTENSIONR01DK039308 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI JOSE, PEDRO A. · 1987 to 2020
$7.4MRenal Dopamine Receptor & RegulationR37HL023081 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI JOSE, PEDRO A. · 2007 to 2016
$4.3MNovel mechanism of smooth muscle phenotypic modulation and vascular remodelingR01HL119053 · NHLBI · UNIVERSITY OF MISSOURI-COLUMBIA · PI CHEN, SHIYOU · 2014 to 2023
$3.8MGRK4 & Development of Salt SensitivityR01HL092196 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI ARMANDO, INES, JOSE, PEDRO A. · 2008 to 2017
$3.6MRole of Dopamine D2 Receptor in Renal Inflammation and InjuryR01DK090918 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI ARMANDO, INES · 2011 to 2015
$1.7MNHLBI NIH HHS P01 HL068686NHLBI NIH HHS P01HL068686NHLBI NIH HHS P01 HL074940NHLBI NIH HHS P01HL074940NHLBI NIH HHS R01 HL092196NHLBI NIH HHS R01HL092196NHLBI NIH HHS R01 HL119053NHLBI NIH HHS R37 HL023081NHLBI NIH HHS R37HL023081NIDDK NIH HHS DK090918NIDDK NIH HHS R01 DK039308NIDDK NIH HHS R01DK039308NIDDK NIH HHS R01 DK090918
Abstract
The influence of a single gene on the pathogenesis of essential hypertension may be difficult to ascertain, unless the gene interacts with other genes that are germane to blood pressure regulation. G-protein-coupled receptor kinase type 4 (GRK4) is one such gene. We have reported that the expression of its variant hGRK4γ(142V) in mice results in hypertension because of impaired dopamine D1 receptor. Signaling through dopamine D1 receptor and angiotensin II type I receptor (AT1R) reciprocally modulates renal sodium excretion and blood pressure. Here, we demonstrate the ability of the hGRK4γ(142V) to increase the expression and activity of the AT1R. We show that hGRK4γ(142V) phosphorylates histone deacetylase type 1 and promotes its nuclear export to the cytoplasm, resulting in increased AT1R expression and greater pressor response to angiotensin II. AT1R blockade and the deletion of the Agtr1a gene normalize the hypertension in hGRK4γ(142V) mice. These findings illustrate the unique role of GRK4 by targeting receptors with opposite physiological activity for the same goal of maintaining blood pressure homeostasis, and thus making the GRK4 a relevant therapeutic target to control blood pressure.
Indexed as
Gene Expression RegulationAngiotensin II Type 1 Receptor BlockersAnimalsBenzimidazolesBiphenyl CompoundsBlood PressureDisease Models, AnimalEssential HypertensionFemaleG-Protein-Coupled Receptor Kinase 4HEK293 CellsHistone Deacetylase 1HumansHypertensionImmunoblottingKidneyAngiotensin II Type 1 Receptor BlockersBenzimidazolesBiphenyl CompoundscandesartanG-Protein-Coupled Receptor Kinase 4GRK4 protein, humanHistone Deacetylase 1Receptor, Angiotensin, Type 1RNATetrazolesangiotensin II type 1 receptordopamine D1 receptorsG-protein–coupled receptor kinase 4histone deacetylasehypertensionknockout mice
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