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G protein-coupled receptor kinase 2 expression and activity are associated with blood pressure in black Americans.

ABSTRACT: 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.

SUBMITTER: Cohn HI

PROVIDER: S-EPMC2745090 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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G protein-coupled receptor kinase 2 expression and activity are associated with blood pressure in black Americans.

Cohn Heather I HI Xi Yihuan Y Pesant Stephanie S Harris David M DM Hyslop Terry T Falkner Bonita B Eckhart Andrea D AD

Hypertension (Dallas, Tex. : 1979) 20090601 1

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 insig ...[more]

PMID: 19487588

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Project description:BACKGROUND:We developed a new model of hypertension care for non-Hispanic black men that links health promotion by barbers to medication management by American Society of Hypertension-certified pharmacists and demonstrated efficacy in a 6-month cluster-randomized trial. The marked reduction in systolic blood pressure (BP) seen at 6 months warranted continuing the trial through 12 months to test sustainability, a necessary precondition for implementation research. METHODS:We enrolled a cohort of 319 black male patrons with systolic BP ?140 mm?Hg at baseline. Fifty-two Los Angeles County barbershops were assigned to either a pharmacist-led intervention or an active control group. In the intervention group, barbers promoted follow-up with pharmacists who prescribed BP medication under a collaborative practice agreement with patrons' primary care providers. In the control group, barbers promoted follow-up with primary care providers and lifestyle modification. After BP assessment at 6 months, the intervention continued with fewer in-person pharmacist visits to test whether the intervention effect could be sustained safely for 1 year while reducing pharmacist travel time. Final BP and safety outcomes were assessed in both groups at 12 months. RESULTS:At baseline, mean systolic BP was 152.4 mm?Hg in the intervention group and 154.6 mm?Hg in the control group. At 12 months, mean systolic BP fell by 28.6 mm?Hg (to 123.8 mm?Hg) in the intervention group and by 7.2 mm?Hg (to 147.4 mm?Hg) in the control group. The mean reduction was 20.8 mm?Hg greater in the intervention (95% CI, 13.9-27.7; P<0.0001). A BP <130/80 mm?Hg was achieved by 68.0% of the intervention group versus 11.0% of the control group ( P<0.02). These new 12-month efficacy data are statistically indistinguishable from our previously reported 6-month data. No treatment-related serious adverse events occurred in either group over 12 months. Cohort retention at 12 months was 90% in both groups. CONCLUSIONS:Among black male barbershop patrons with uncontrolled hypertension, health promotion by barbers resulted in large and sustained BP reduction over 12 months when coupled with medication management by American Society of Hypertension-certified pharmacists. Broad-scale implementation research is both justified and warranted. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov . Unique identifier: NCT 02321618.

Dataset Information

G protein-coupled receptor kinase 2 expression and activity are associated with blood pressure in black Americans.

Publications

G protein-coupled receptor kinase 2 expression and activity are associated with blood pressure in black Americans.

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