Hypertension is a prevalent condition in the developed world and disease severity is directly correlated with additional cardiovascular complications. It is estimated that 30% of the adult population in the United States has hypertension, which is classified as a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg. A prolonged increase in afterload ultimately leads to congestive heart failure in the majority of cases. Currently, medication designed to treat hypertension is inadequate, thus new therapies need to be explored. Blood pressure is tightly regulated by blood vessel radius, which is established by hormones and/or peptides binding to GPCRs (G-protein-coupled receptors). Catecholamines and peptide hormones, such as AngII (angiotensin II), are elevated in hypertension and, therefore, signalling by these GPCRs is increased. Their signalling is tightly controlled by a class of proteins, the GRKs (GPCR kinases). Elevated levels of either GRK2 or GRK5 in both the lymphocytes and VSM (vascular smooth muscle) are associated with human hypertension and animal models of the disease. The focus of the present review is on the role GRKs, and their regulation of GPCRs, play in high blood pressure.
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August 2008
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Review Article|
July 02 2008
GPCR signalling in hypertension: role of GRKs
David M. Harris;
David M. Harris
1Eugene Feiner Laboratory for Vascular Biology and Thrombosis, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA 19107, U.S.A.
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Heather I. Cohn;
Heather I. Cohn
1Eugene Feiner Laboratory for Vascular Biology and Thrombosis, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA 19107, U.S.A.
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Stéphanie Pesant;
Stéphanie Pesant
1Eugene Feiner Laboratory for Vascular Biology and Thrombosis, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA 19107, U.S.A.
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Andrea D. Eckhart
1Eugene Feiner Laboratory for Vascular Biology and Thrombosis, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA 19107, U.S.A.
Correspondence: Dr Andrea D. Eckhart (andrea.eckhart@jefferson.edu).
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Publisher: Portland Press Ltd
Received:
December 11 2007
Revision Received:
January 17 2008
Accepted:
February 13 2008
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2008 Biochemical Society
2008
Clin Sci (Lond) (2008) 115 (3): 79–89.
Article history
Received:
December 11 2007
Revision Received:
January 17 2008
Accepted:
February 13 2008
Citation
David M. Harris, Heather I. Cohn, Stéphanie Pesant, Andrea D. Eckhart; GPCR signalling in hypertension: role of GRKs. Clin Sci (Lond) 1 August 2008; 115 (3): 79–89. doi: https://doi.org/10.1042/CS20070442
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