Regulation of Renal Hemodynamics and Function by RGS2

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 μl/min/g body weight, p<0.01). RBF was reduced (35.4 ± 3.6 vs. 29.1 ± 2.1 μl/min/g body weight, p=0.08) while renal vascular resistance (RVR; 2.1 ± 0.2 vs. 3.0 ± 0.2 mmHg/μl/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.

RGS 2 squelches vascular G i/o and G q signaling to modulate myogenic tone and promote uterine blood flow

“…; Osei‐Owusu et al. ). Therefore, we determined whether RGS2 deficiency affects uterine artery blood flow.…”

Proteolytic degradation of regulator of G protein signaling 2 facilitates temporal regulation of Gq/11 signaling and vascular contraction

“…RGS2 is a GAP that acts preferentially toward G q/11 class ␣-subunits relative to G i/o ␣-subunits (9 -12), and has several GAP-independent functions (8,13,14). RGS2 is expressed in many organs, tissues, and cell types where it participates in diverse physiological and disease processes including T cell activation (15), blood pressure regulation (16 -20), cardiac hypertrophy and heart failure (21)(22)(23), renal hemodynamics (20), anxiety (15,24), and certain cancers (25).…”

Optimization of Non-Thermal Plasma Treatment in an In Vivo Model Organism

“…Future work in this context will be to test individual components separately to determine the constituent causing the increasing in ROS in blood cells. However, based on previous work, we speculate that superoxide might be the major candidate for Drosophila blood cells given it is established that genetic depletion of superoxide dismutase enzyme increased ROS and differentiation [ 15 ].…”

“…The lymph gland were then mounted in PBS and immediately photographed under a Zeiss confocal microscope. ROS levels were quantified by measuring integrated intensities [ 15 ] from treated and untreated lymph glands.…”