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Molecular and Cellular Biology, April 2008, p. 2590-2597, Vol. 28, No. 8
0270-7306/08/$08.00+0     doi:10.1128/MCB.01889-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Rgs5 Targeting Leads to Chronic Low Blood Pressure and a Lean Body Habitus{triangledown}

Hyeseon Cho,1* Chung Park,1 Il-Young Hwang,1 Sang-Bae Han,2 Dan Schimel,3 Daryl Despres,3 and John H. Kehrl1*

B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases,1 Mouse Imaging Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1876,3 College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea2

Received 18 October 2007/ Returned for modification 7 December 2007/ Accepted 29 January 2008

RGS5 is a potent GTPase-activating protein for Gi{alpha} and Gq{alpha} that is expressed strongly in pericytes and is present in vascular smooth muscle cells. To study the role of RGS5 in blood vessel physiology, we generated Rgs5-deficient mice. The Rgs5–/– mice developed normally, without obvious defects in cardiovascular development or function. Surprisingly, Rgs5–/– mice had persistently low blood pressure, lower in female mice than in male mice, without concomitant cardiac dysfunction, and a lean body habitus. The examination of the major blood vessels revealed that the aortas of Rgs5–/– mice were dilated compared to those of control mice, without altered wall thickness. Isolated aortic smooth muscle cells from the Rgs5–/– mice exhibited exaggerated levels of phosphorylation of vasodilator-stimulated phosphoprotein and extracellular signal-regulated kinase in response to stimulation with either sodium nitroprusside or sphingosine 1-phosphate. The results of this study, along with those of previous studies demonstrating that RGS5 stability is under the control of nitric oxide via the N-end rule pathway, suggest that RGS5 may balance vascular tone by attenuating vasodilatory signaling in vivo in opposition to RGS2, another RGS (regulator of G protein signaling) family member known to inhibit G protein-coupled receptor-mediated vasoconstrictor signaling. Blocking the function or the expression of RGS5 may provide an alternative approach to treat hypertension.

* Corresponding author. Mailing address: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 10, Room 11B08, 10 Center Dr. MSC 1876, Bethesda, MD 20892. Phone for Hyeseon Cho: (301) 496-6363. Fax: (301) 402-0070. E-mail: hcho{at}niaid.nih.gov. Phone for John H. Kehrl: (301) 443-6907. Fax: (301) 402-0070. E-mail: jkehrl{at}niaid.nih.gov

{triangledown} Published ahead of print on 11 February 2008.

Molecular and Cellular Biology, April 2008, p. 2590-2597, Vol. 28, No. 8
0270-7306/08/$08.00+0     doi:10.1128/MCB.01889-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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