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Journal article
Regulation of Renal Hemodynamics and Function by RGS2
PloS one, v 10(7), pp e0132594-e0132594
20 Jul 2015
PMID: 26193676
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Regulator of G protein signaling 2 (RGS2) controls G protein coupled receptor (GPCR) signaling by acting as a GTPase-activating protein for heterotrimeric G proteins. Certain Rgs2 gene mutations have been linked to human hypertension. Renal RGS2 deficiency is sufficient to cause hypertension in mice; however, the pathological mechanisms are unknown. Here we determined how the loss of RGS2 affects renal function. We examined renal hemodynamics and tubular function by monitoring renal blood flow (RBF), glomerular filtration rate (GFR), epithelial sodium channel (ENaC) expression and localization, and pressure natriuresis in wild type (WT) and RGS2 null (RGS2-/-) mice. Pressure natriuresis was determined by stepwise increases in renal perfusion pressure (RPP) and blood flow, or by systemic blockade of nitric oxide synthase with L-NG-Nitroarginine methyl ester (L-NAME). Baseline GFR was markedly decreased in RGS2-/-mice compared to WT controls (5.0 +/- 0.8 vs. 2.5 +/- 0.1 mu l/min/g body weight, p<0.01). RBF was reduced (35.4 +/- 3.6 vs. 29.1 +/- 2.1 mu l/min/g body weight, p=0.08) while renal vascular resistance (RVR; 2.1 +/- 0.2 vs. 3.0 +/- 0.2 mmHg/mu l/min/g body weight, p<0.01) was elevated in RGS2-/-compared to WT mice. RGS2 deficiency caused decreased sensitivity and magnitude of changes in RVR and RBF after a step increase in RPP. The acute pressure-natriuresis curve was shifted rightward in RGS2-/-relative to WT mice. Sodium excretion rate following increased RPP by L-NAME was markedly decreased in RGS2-/-mice and accompanied by increased translocation of ENaC to the luminal wall. We conclude that RGS2 deficiency impairs renal function and autoregulation by increasing renal vascular resistance and reducing renal blood flow. These changes impair renal sodium handling by favoring sodium retention. The findings provide a new line of evidence for renal dysfunction as a primary cause of hypertension.
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Details
- Title
- Regulation of Renal Hemodynamics and Function by RGS2
- Creators
- Patrick Osei-Owusu - Drexel UniversityElizabeth A. Owens - Drexel UniversityLi Jie - Drexel UniversityJanaina S. Reis - Drexel UniversitySteven J. Forrester - Temple UniversityTatsuo Kawai - Temple UniversitySatoru Eguchi - Temple UniversityHarpreet Singh - Drexel UniversityKendall J. Blumer - Washington University in St. Louis
- Publication Details
- PloS one, v 10(7), pp e0132594-e0132594
- Publisher
- Public Library Science
- Number of pages
- 20
- Grant note
- R01HL075632 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) 13GRNT17060036 / American Heart Association HL075632; GM44592 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01GM044592 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) Washington University O'Brien Kidney Center
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000358546400033
- Scopus ID
- 2-s2.0-84941287208
- Other Identifier
- 991019167619804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Physiology