Dihydropyridine calcium channel blockers inhibit free fatty acid-induced endothelial and rheological dysfunction.

Circulating free fatty acids (FFAs) from adipose tissue lipolysis lead to endothelial dysfunction and insulin resistance in patients with metabolic syndrome or type II diabetes mellitus. The aim of this study was to test the hypothesis that dihydropyridine calcium channel blockers prevent FFA-induced endothelial and hemo-rheological dysfunction independently of their antihypertensive properties. Using a double-blind, crossover study design, nifedipine, amlodipine, diltiazem or placebo were administered to 8 healthy subjects for 2 days before each study day. On study days, the following were assessed before and after infusion of lipid and heparin to raise serum FFA: endothelial function, by measuring forearm blood flow responses to acetylcholine (ACh); leukocyte activation, by ex vivo measurement of plasma myeloperoxidase levels, adherent leukocyte numbers and whole blood transit time through microchannels; and oxidative stress, by determining plasma levels of derivatives of reactive oxygen metabolites (d-ROMs). Effects of the calcium channel blockers on NFkB p65 phospholylation stimulated by FFA were assessed in cultured monocytic cells in vitro. Elevated FFA reduced the responses to ACh and significantly increased whole blood transit time, adherent leukocyte numbers and d-ROMs. Nifedipine and amlodipine, but not diltiazem, prevented FFA-induced endothelial dysfunction, leukocyte activation and enhancement of oxidative stress without affecting blood pressure, while all drugs ...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research