ArticleClinical science (London, England : 1979)2020
GRK4-mediated adiponectin receptor-1 phosphorylative desensitization as a novel mechanism of reduced renal sodium excretion in hypertension.
Article in Clinical science (London, England : 1979), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 23 citations in OpenAlex.
- Effects of DASH diet with or without time-restricted eating in the management of stage 1 primary hypertension: a randomized controlled trial.Nutrition journal · 2024Trial
- Causal demonstration of adiposity-induced adipose-specific signaling derangements in the pathogenesis of the clinical features of the cardiovascular-kidney metabolic syndrome.Cardiovascular diabetology · 2026Review
- Uncovering Hippo pathway-related biomarkers in acute myocardial infarction via scRNA-seq binding transcriptomics.Scientific reports · 2025Article
- Selenium deficiency causes hypertension by increasing renal ATFree radical biology & medicine · 2023Article
- Dopamine Receptor DThe Yale journal of biology and medicine · 2023Review
- Adiponectin, Leptin and Resistin in Patients with Psoriasis.Journal of clinical medicine · 2023Article
- Role of Adiponectin in Cardiovascular Diseases Related to Glucose and Lipid Metabolism Disorders.International journal of molecular sciences · 2022Review
- Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics.Pharmacology & therapeutics · 2022Review
- Adiponectin System (Rescue Hormone): The Missing Link between Metabolic and Cardiovascular Diseases.Pharmaceutics · 2022Review
- Synergistic Effect of Uroguanylin and DJournal of the American Heart Association · 2022Article
- QR code model: a new possibility for GPCR phosphorylation recognition.Cell communication and signaling : CCS · 2022Review
- Paternal long-term PM2.5 exposure causes hypertension via increased renal AT1R expression and function in male offspring.Clinical science (London, England : 1979) · 2021Article
- Identification of key pathways and genes in polycystic ovary syndrome via integrated bioinformatics analysis and prediction of small therapeutic molecules.Reproductive biology and endocrinology : RB&E · 2021Article
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Hypertensive patients have impaired sodium excretion. However, the mechanisms are incompletely understood. Despite the established association between obesity/excess adiposity and hypertension, whether and how adiponectin, one of the adipokines, contributes to impaired sodium excretion in hypertension has not been previously investigated. The current study tested the hypothesis that adiponectin promotes natriuresis and diuresis in the normotensive state. However, impaired adiponectin-mediated natriuresis and diuresis are involved in pathogenesis of hypertension. We found that sodium excretion was reduced in adiponectin knockout (Adipo-/-) mice; intrarenal arterial infusion of adiponectin-induced natriuresis and diuresis in Wistar-Kyoto (WKY) rats. However, the natriuretic and diuretic effects of adiponectin were impaired in spontaneously hypertensive rats (SHRs), which were ascribed to the hyperphosphorylation of adiponectin receptor and subsequent uncoupling from Gαi. Inhibition of adiponectin receptor phosphorylation by a specific point mutation restored its coupling with Gαi and the adiponectin-mediated inhibition of Na+-K+-ATPase activity in renal proximal tubule (RPT) cells from SHRs. Finally, we identified G protein-coupled receptor kinase 4 (GRK4) as a mediator of adiponectin receptor hyperphosphorylation; mice transgenic for a hyperphosphorylating variant of GRK4 replicated the abnormal adiponectin function observed in SHRs, whereas down-regulation of GRK4 by renal ultrasound-directed small interfering RNA (siRNA) restored the adiponectin-mediated sodium excretion and reduced the blood pressure in SHRs. We conclude that the stimulatory effect of adiponectin on sodium excretion is impaired in hypertension, which is ascribed to the increased renal GRK4 expression and activity. Targeting GRK4 restores impaired adiponectin-mediated sodium excretion in hypertension, thus representing a novel strategy against hypertension.
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