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• W2019475812 abstract "Peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear transcription factor, modulates the expression/activity of G protein-coupled receptors (GPCRs), but its role in GPCR signaling is not clear. Increased GPCR kinase-2 (GRK-2) activity and receptor desensitization have been reported in hypertension.In this study we investigated the role of GRK-2 in PPARgamma-mediated blood pressure regulation in hypertension. SHR or WKY rats were treated with GW1929, a selective PPARgamma ligand (0.5 mg/kg/day), or vehicle for 2 months. Systolic blood pressure (tail cuff plethysmography), whole kidney perfusion (laser scanner) and renal vascular reactivity (isolated perfused kidney) was determined.GW1929 significantly reduced blood pressure (20 +/- 1%) and increased renal perfusion (61 +/- 3%) in SHR compared to WKY rats. Vasoconstriction to phenylephrine (100 microg) in the isolated perfused kidney was greater in SHRs (29 +/- 1%) compared to WKY rats and this was abolished by GW1929. GW1929 enhanced acetylcholine-induced (30-300 microg) and sodium nitroprusside-induced vasodilatation in SHR by 46 +/- 2% (p < 0.05) and 33 +/- 2% (p < 0.05), respectively. Isoprenalin-induced (5-30 microg) vasodilatation was 43 +/- 2% lower in SHR compared to WKY and GW1929 enhanced this vasodilatation by 55 +/- 2%. In SHR kidney, GW1929 enhanced expression of PPARgamma mRNA (34 +/- 1%) but reduced that of GRK-2 (31 +/- 3%).We suggest that downregulation of PPARgamma but upregulation of GRK-2 increases blood pressure and impaired renal vascular reactivity in SHR and that PPARgamma-mediated improvement in hypertension may involve transcriptional regulation of GRK-2 function." @default.
• W2019475812 created "2016-06-24" @default.
• W2019475812 creator A5062614021 @default.
• W2019475812 creator A5070994148 @default.
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• W2019475812 date "2009-01-01" @default.
• W2019475812 modified "2023-10-14" @default.
• W2019475812 title "Role of G Protein-Coupled Receptor Kinase-2 in Peroxisome Proliferator-Activated Receptor Gamma-Mediated Modulation of Blood Pressure and Renal Vascular Reactivity in SHR" @default.
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• W2019475812 doi "https://doi.org/10.1159/000218061" @default.
• W2019475812 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2820323" @default.
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