Hypertension and Prolonged Vasoconstrictor Signaling in RGS2-deficient Mice

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2003 Feb 18

PMID 12588882

Citations 96

Authors

Scott P Heximer

Russell H Knutsen

Xiaoguang Sun

Kevin M Kaltenbronn

Man-Hee Rhee

Ning Peng

Antonio Oliveira-Dos-Santos

Josef M Penninger

Anthony J Muslin

Thomas H Steinberg

J Michael Wyss

Robert P Mecham

Kendall J Blumer

Affiliations

Soon will be listed here.

Abstract

Signaling by hormones and neurotransmitters that activate G protein-coupled receptors (GPCRs) maintains blood pressure within the normal range despite large changes in cardiac output that can occur within seconds. This implies that blood pressure regulation requires precise kinetic control of GPCR signaling. To test this hypothesis, we analyzed mice deficient in RGS2, a GTPase-activating protein that greatly accelerates the deactivation rate of heterotrimeric G proteins in vitro. Both rgs2+/- and rgs2-/- mice exhibited a strong hypertensive phenotype, renovascular abnormalities, persistent constriction of the resistance vasculature, and prolonged response of the vasculature to vasoconstrictors in vivo. Analysis of P2Y receptor-mediated Ca2+ signaling in vascular smooth muscle cells in vitro indicated that loss of RGS2 increased agonist potency and efficacy and slowed the kinetics of signal termination. These results establish that abnormally prolonged signaling by G protein-coupled vasoconstrictor receptors can contribute to the onset of hypertension, and they suggest that genetic defects affecting the function or expression of RGS2 may be novel risk factors for development of hypertension in humans.

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