Renal actions of RGS2 control blood pressure.
G protein-coupled receptors (GPCRs) have key roles in cardiovascular regulation and are important targets for the treatment of hypertension. GTPase-activating proteins, such as RGS2, modulate downstream signaling by GPCRs. RGS2 displays regulatory selectivity for the Gαq subclass of G proteins, and mice lacking RGS2 develop hypertension through incompletely understood mechanisms. Using total body RGS2-deficient mice, we used a kidney crosstransplantation strategy to examine separately the contributions of RGS2 actions in the kidney from those in extrarenal tissues with regard to BP regulation. Loss of renal RGS2 was sufficient to cause hypertension, whereas the absence of RGS2 from all extrarenal tissues including the peripheral vasculature did not significantly alter BP. Accordingly, these results suggest that RGS2 acts within the kidney to modulate BP and prevent hypertension. These data support a critical role for the renal epithelium and/or vasculature as the final determinants of the intra-arterial pressure in hypertension.
Gurley
Susan B
SB
Department of Medicine, Division of Nephrology, Duke University Medical Center, Durham, NC 27710, USA.
Griffiths
Robert C
RC
Mendelsohn
Michael E
ME
Karas
Richard H
RH
Coffman
Thomas M
TM
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000502:physiology*; D016030:Kidney Transplantation / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020710:RGS Proteins / Q000235:genetics / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology
D020710:RGS Proteins; D043562:Receptors, G-Protein-Coupled; C105345:Rgs2 protein, mouse