
February 2003 From Journal of Clinical Investigation Keeping blood pressure in check Hypertension - the presence of persistently high blood pressure – is a leading mortality risk factor in Western populations. More than half of Americans over 50 years of age have hypertension and almost one quarter of the US population (about 50 million people) experience hypertension to some degree.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: [email protected] View the PDF of this article at: https://www.the-jci.org/press/15598.pdf 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: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/17836.pdf |