Document Detail


G protein-coupled receptor kinase 2 expression and activity are associated with blood pressure in black Americans.
MedLine Citation:
PMID:  19487588     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypertension occurs with higher prevalence and morbidity in black Americans compared with other groups. Alterations in the signal transduction pathways of 7-transmembrane spanning receptors are found in hypertensive patients. G protein-coupled receptor kinases (GRKs) play an important role in regulating this receptor signaling. The 2 most abundantly expressed GRKs in the cardiovascular system are GRK2 and GRK5, and each has unique substrates. Understanding changes in expression may give us insight into activated receptors in the pathophysiological progression of hypertension. In heart failure and white hypertensives, increased GRK2 expression arises because of neurohormonal stimulation of particular receptors. GRK2 subsequently desensitizes specific receptors, including beta-adrenergic receptors. In blood pressure control, beta-adrenergic receptor desensitization could lead to increased blood pressure. GRK2 and GRK5 mRNA were evaluated in lymphocytes of black Americans via quantitative real-time PCR. GRK2 mRNA expression directly correlated with systolic blood pressure and norepinephrine levels. GRK2 was elevated >30% among those with systolic blood pressure > or =130 mm Hg. No significant correlation between GRK5 mRNA expression and blood pressure or catecholamines was observed. Diabetic status, age, sex, and body mass index were also compared with GRK2 expression using univariate and multivariate analyses. GRK2 protein expression was elevated 2-fold in subjects with higher blood pressure, and GRK activity was increased >40%. Our data suggest that GRK2, but not GRK5, is correlated with increasing blood pressure in black Americans. Understanding the receptors stimulated by increased neurohormonal activation may give insight into the pathophysiology of hypertension in this at-risk population.
Authors:
Heather I Cohn; Yihuan Xi; Stephanie Pesant; David M Harris; Terry Hyslop; Bonita Falkner; Andrea D Eckhart
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-06-01
Journal Detail:
Title:  Hypertension     Volume:  54     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-18     Completed Date:  2009-09-16     Revised Date:  2012-06-07    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  71-6     Citation Subset:  IM    
Affiliation:
Center for Translational Medicine, Thomas Jefferson Hospital, Philadelphia, PA, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
African Americans / statistics & numerical data*
Aged
Blood Pressure / physiology*
Cohort Studies
Female
G-Protein-Coupled Receptor Kinase 2 / genetics,  metabolism*
G-Protein-Coupled Receptor Kinase 5 / genetics,  metabolism*
Gene Expression Regulation, Enzymologic
Humans
Hypertension / enzymology,  ethnology,  physiopathology
Immunoassay
Immunoblotting
Male
Middle Aged
Multivariate Analysis
Norepinephrine / blood
Prevalence
RNA, Messenger / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
United States / epidemiology
Young Adult
Grant Support
ID/Acronym/Agency:
R01 DK046107-08/DK/NIDDK NIH HHS; R01 DK046107-09/DK/NIDDK NIH HHS; R01 DK046107-10/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 51-41-2/Norepinephrine; EC 2.7.11.15/ADRBK1 protein, human; EC 2.7.11.15/G-Protein-Coupled Receptor Kinase 2; EC 2.7.11.16/G-Protein-Coupled Receptor Kinase 5; EC 2.7.11.16/GRK5 protein, human
Comments/Corrections
Comment In:
Hypertension. 2009 Jul;54(1):27-8   [PMID:  19487585 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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