Key result
Valsartan and candesartan completely prevented Ang II-induced increases in endothelin, PAI-1, and MMP-1 precursor in human coronary artery endothelial cells at 10 microM concentrations.
Why the study?
Do valsartan and candesartan inhibit deteriorating effects of angiotensin II on coronary endothelial function in human coronary artery endothelial cell cultures?
Do valsartan and candesartan inhibit deteriorating effects of angiotensin II on coronary endothelial function in human coronary artery endothelial cell cultures?
Valsartan and candesartan prevent Ang II-induced increases in endothelin, PAI-1, and MMP-1 in human coronary endothelial cells, suggesting potential benefits in preventing atherogenesis and plaque instability.
Hypothesis-generating for ARB endothelial protection; leaves open clinical translation to atheroprotection.
The angiotensin II (Ang II) AT1-receptor antagonists, valsartan and candesartan, were compared with regard to their effect on Ang II-mediated changes in parameters of coronary endothelial function. Ang II (10 microM) induced increased concentrations of the vasoconstrictor endothelin, the procoagulatory substance plasminogen-activator-inhibitor-1 (PAI-1) and the precursor of the matrix-metalloproteinase 1 (MMP-1) in endothelial cell cultures from human coronary arteries. These increases were completely prevented by the addition of 10 microM valsartan or candesartan and partially by the addition of lower concentrations of these drugs, i.e. 1 microM and 0.1 microM. No significant difference between the effect of the two AT1-receptor antagonists was observed. These results suggest that AT1-receptor antagonists not only can reduce blood pressure by blocking the action of Ang II, but might also contribute to the prevention of atherogenesis and plaque instability.
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Seeger et al. (2001) studied Endothelial cell cultures from human coronary arteries. Valsartan and candesartan vs. Angiotensin II alone was evaluated on Ang II-mediated changes in parameters of coronary endothelial function (endothelin, PAI-1, MMP-1 precursor). Valsartan and candesartan completely prevented Ang II-induced increases in endothelin, PAI-1, and MMP-1 precursor in human coronary artery endothelial cells at 10 microM concentrations.
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