G protein-coupled receptor kinase 2 expression and activity are associated with blood pressure in black Americans.
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.
Cohn
Heather I
HI
Center for Translational Medicine, Thomas Jefferson Hospital, Philadelphia, PA, USA.
Xi
Yihuan
Y
Pesant
Stephanie
S
Harris
David M
DM
Hyslop
Terry
T
Falkner
Bonita
B
Eckhart
Andrea D
AD
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data*; D000368:Aged; D001794:Blood Pressure / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics / Q000378:metabolism*; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000208:ethnology / Q000503:physiopathology; D007118:Immunoassay; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009638:Norepinephrine / Q000097:blood; D015995:Prevalence; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014481:United States / Q000453:epidemiology; D055815:Young Adult
D012333:RNA, Messenger; C496567:GRK2 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2; D054774:G-Protein-Coupled Receptor Kinase 5; C517898:GRK5 protein, human; D009638:Norepinephrine