The constriction and dilation of blood vessels is partially controlled by G protein–coupled receptors (GPCRs), which are activated by many important cardiovascular hormones. RGS proteins, a family of more than 20 regulators of GPCR signaling, promote the deactivation of GPCRs and therefore may have a role in the regulation of blood pressure.
Kendall Blumer and colleagues at the Washington University School of Medicine in St. Louis, Missouri, analyzed mice deficient in a specific member of this regulatory family - RGS2 - and found that these mice were strongly hypertensive and exhibited persistent vessel constriction. Pharmacological studies revealed that the loss of RGS2 slowed the termination of signals that induce blood vessel constriction. This suggests that abnormally prolonged GPCR signaling can contribute to the onset of high blood pressure. Genetic defects in humans that affect RGS2 function may therefore be novel risk factors for the development of hypertension.
In the same issue, Dr. Thomas Coffman from Duke University and the Veterans Administration Medical Center in Durham, North Carolina, states in his accompanying commentary that "the level of blood pressure elevation in the RGS2-deficient animals is quite striking". The researchers also found that even mice that retained one copy of the rgs2 gene were still unable to compensate for the loss of the RG2 protein, and presented with hypertension. "The presence of hypertension in these animals suggests that naturally occurring mutations that only incrementally affect the level of RGS2 protein may have a significant impact on blood pressure regulation. The studies clearly show that RGS2 is an important regulatory element", indicated Dr. Coffman. Identification of abnormalities in GPCR signaling may lead to new means of diagnosing genetic causes of hypertension and the development of suitable therapies.
CONTACT:
Kendall J. Blumer
Department of Cell Biology and Physiology
Washington University School of Medicine
660 S. Euclid Avenue
St. Louis, Missouri 63110
USA
PHONE: 314-362-1668
FAX: 314-362-7463
E-mail: kblumer@cellbio.wustl.edu
View the PDF of this article at: http://www.jci.org/cgi/content/full/111/4/445
ACCOMPANYING COMMENTARY:
RGS2: a "turn off" in hypertension
CONTACT:
Thomas M. Coffman
Durham Veterans Administration Medical Center
Building 6/Nephrology, Room 1100
508 Fulton Street
Durham, North Carolina 27705
USA
PHONE: 919-286-6947
FAX: 919-286-6879
E-mail: tcoffman@duke.edu
Journal of Clinical Investigation