Elevations in C-reactive protein and endothelin-1 system activity in humans.

Abstract:

AIMS:C-reactive protein (CRP) is an inflammatory cytokine that has been shown to be an independent predictor of future atherothrombotic events. Hyperactivity of endothelin-1 (ET-1), a potent vasoconstrictor peptide produced by the endothelium, is linked with cardiovascular disease development and progression. ET-1 is sensitive to inflammatory stimuli, though the influence of CRP on ET-1 system activity is unknown. We tested the hypothesis that ET-1-mediated vasoconstrictor tone is enhanced in adults with elevated plasma CRP concentrations. MATERIALS AND METHODS:Sixty non-obese adults (43-70years) were studied: 20 with hsCRP<1.0mg/L (low CRP; 0.5±0.1mg/L); 20 with hsCRP 1.0-3.0mg/L (moderate CRP; 2.0±0.1mg/L); and 20 with hsCRP>3.0mg/L (high CRP; 6.3±0.5mg/L). Forearm blood flow (FBF; plethysmography) was determined in response to intra-arterial infusions of ET-1 (5pmol/min for 20min) and selective ETA receptor blockade (BQ-123, 100nmol/min for 60min). KEY FINDINGS:In response to ET-1, FBF decreased ~10% in the low (-10.0±2.3%), moderate (-10.7±4.0%), and high (-6.6±5.2%) CRP groups, with no significant differences between groups. Additionally, all groups demonstrated a marginal, though significant (~10%), vasodilator response to BQ-123; however, there were no differences in the FBF response to BQ-123 across CRP groups. There were no significant correlations between plasma CRP concentrations and peak FBF response to either ET-1 or BQ-123. SIGNIFICANCE:These results indicate that ET-1 system activity is not influenced by elevations in CRP. Enhanced ET-1 system activity may not be involved in the increased cardiovascular disease risk associated with elevations in plasma CRP concentrations.

journal_name

Life Sci

journal_title

Life sciences

authors

Dow CA,Templeton DL,Lincenberg GM,Greiner JJ,Stauffer BL,DeSouza CA

doi

10.1016/j.lfs.2015.12.030

subject

Has Abstract

pub_date

2016-08-15 00:00:00

pages

66-70

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(15)30123-5

journal_volume

159

pub_type

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