Hypertensive left ventricular hypertrophy: relation to beta-adrenergic receptor kinase-1 (betaARK1) in peripheral lymphocytes

J Hypertens. 2004 May;22(5):1025-32. doi: 10.1097/00004872-200405000-00026.

Abstract

Background: Left ventricular hypertrophy (LVH) is associated with increased cardiovascular risk and altered sympathetic regulation in hypertension.

Objectives: To determine whether the level of beta-adrenergic receptor kinase-1 (betaARK1) in lymphocytes is related to LVH in patients with hypertension.

Methods: Forty-nine patients with untreated essential hypertension were recruited to the study and classified into two groups: left ventricular hypertrophy (LVH: left ventricular mass index > or =134 g/m in men and > or =110 g/m in women; ages 52.4 +/- 12.8 years, n = 25) and non-LVH (NLVH: left ventricular mass index < 134 g/m in men and < 110 g/m in women; ages 50.8 +/- 13.1 years, n = 24). Lymphocytes were isolated from patients and quantitative-competitive reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting were used to estimate the expression of betaARK1 in the lymphocytes. G-protein-coupled receptor kinase activity was assessed by rhodopsin phosphorylation assay.

Results: The expression of betaARK1 in lymphocytes was greater in the LVH group than in the NLVH group (0.0069 +/- 0.002 ng compared with 0.0048 +/- 0.0017 ng, P < 0.01) and correlated well with left ventricular mass index (r = 0.527, P < 0.001) and relative wall thickness (r = 0.627, P < 0.001). The concentration of betaARK1 protein in lymphocytes from individuals with LVH was increased two-fold compared with that in the NLVH group (both n = 7). Lymphocyte G-protein-coupled receptor kinase activity from LVH was enhanced 1.7-fold compared with NLVH (1.03 +/- 2.16 and 1.79 +/- 1.87 pmol phosphate/min per mg protein, respectively; P < 0.05, n = 7 for each group).

Conclusions: The concentration of betaARK1 in lymphocytes is greater in hypertensive individuals with LVH than in those without LVH and parallels the degree of hypertrophy. Generalized alterations in beta-adrenergic signalling, including betaARK1, could be a major contributory factor in the development of LVH in hypertension, and the concentration of betaARK1 in lymphocytes can reflect the development of LVH in a patient with hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cyclic AMP-Dependent Protein Kinases / genetics*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Echocardiography
  • Enzyme Activation / immunology
  • Female
  • G-Protein-Coupled Receptor Kinase 2
  • Humans
  • Hypertension / complications*
  • Hypertrophy, Left Ventricular / diagnostic imaging
  • Hypertrophy, Left Ventricular / immunology*
  • Hypertrophy, Left Ventricular / metabolism*
  • Lymphocytes / enzymology*
  • Male
  • Middle Aged
  • beta-Adrenergic Receptor Kinases

Substances

  • Cyclic AMP-Dependent Protein Kinases
  • GRK2 protein, human
  • beta-Adrenergic Receptor Kinases
  • G-Protein-Coupled Receptor Kinase 2