Amelioration of genetic hypertension by suppression of renal G protein-coupled receptor kinase type 4 expression

Hypertension
H SanadaPedro A Jose

Abstract

Abnormalities in D1 dopamine receptor function in the kidney are present in some types of human essential and rodent genetic hypertension. We hypothesize that increased activity of G protein-coupled receptor kinase type 4 (GRK4) causes the impaired renal D1 receptor function in hypertension. We measured renal GRK4 and D1 and serine-phosphorylated D1 receptors and determined the effect of decreasing renal GRK4 protein by the chronic renal cortical interstitial infusion (4 weeks) of GRK4 antisense oligodeoxynucleotides (As-Odns) in conscious- uninephrectomized spontaneously hypertensive rats (SHRs) and their normotensive controls, Wistar-Kyoto (WKY) rats. Basal GRK4 expression and serine-phosphorylated D1 receptors were &90% higher in SHRs than in WKY rats and were decreased to a greater extent in SHRs than in WKY rats with GRK4 As-Odns treatment. Basal renal D1 receptor protein was similar in both rat strains. GRK4 As-Odns, but not scrambled oligodeoxynucleotides, increased sodium excretion and urine volume, attenuated the increase in arterial blood pressure with age, and decreased protein excretion in SHRs, effects that were not observed in WKY rats. These studies provide direct evidence of a crucial role of renal GRK4 in the D...Continue Reading

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Citations

Jul 11, 2008·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Xiaoyan WangPedro A Jose
Mar 13, 2012·Current Hypertension Reports·Raymond C Harris, Ming-Zhi Zhang
Oct 27, 2006·Nature Clinical Practice. Nephrology·Robin A Felder, Pedro A Jose
Jun 13, 2009·The Journal of Biological Chemistry·Van Anthony M VillarPedro A Jose
Feb 6, 2010·Clinical and Experimental Pharmacology & Physiology·Yu-Rong Zhang, Zu-Yi Yuan
Feb 20, 2007·Annual Review of Physiology·Richard T Premont, Raul R Gainetdinov
Sep 4, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Crisanto S EscanoPedro A Jose
Feb 4, 2011·American Journal of Physiology. Renal Physiology·John J GildeaRobin A Felder
Oct 26, 2012·American Journal of Physiology. Renal Physiology·Gaurav ChughMohammad Asghar
Mar 19, 2008·Hypertension·Chunyu ZengPedro A Jose
Aug 20, 2008·Hypertension·Peter A Doris
Oct 30, 2008·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Junichi YatabePedro A Jose
Dec 18, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Chunyu ZengPedro A Jose
Oct 16, 2012·Trends in Cardiovascular Medicine·Fadia A KamalBurns C Blaxall
Sep 10, 2011·Pharmacology & Therapeutics·Eugenia V GurevichVsevolod V Gurevich
Nov 21, 2014·Clinical and Experimental Nephrology·Midori Sasaki YatabeTsuyoshi Watanabe
Feb 16, 2010·Biochimica Et Biophysica Acta·Pedro A JoseRobin A Felder
Nov 15, 2016·Journal of Hypertension·Brian L Rayner, J David Spence
Jul 9, 2016·Journal of the American Heart Association·Jian YangChunyu Zeng
Apr 15, 2015·Hypertension·Jian YangChunyu Zeng
Jan 31, 2019·Clinical and Experimental Hypertension : CHE·Dongdong SunChunyu Zeng
Jan 30, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Zheng WangPedro A Jose
Feb 7, 2014·American Journal of Physiology. Renal Physiology·Shaoxiong WangChunyu Zeng
Aug 7, 2017·Current Hypertension Reports·Andrew C TiuVan Anthony M Villar
Dec 1, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Van Anthony M VillarJohn E Jones
May 12, 2007·Clinical Science·Chunyu ZengPedro A Jose
May 1, 2020·Antioxidants & Redox Signaling·Jian YangChunyu Zeng
Jul 21, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yang YangYukai Liu
Dec 8, 2020·European Heart Journal·Rajika Roy, Walter J Koch

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