Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · May 2006
Statins blunt thrombin-induced down-regulation of endothelial nitric oxide synthase expression in human endothelial cells.
Thrombin plays a pivotal role in the pathophysiology of acute coronary syndromes by mediating thrombus formation and endothelium-dependent vasomotor dysfunction. In human endothelial cells, prolonged incubation with thrombin down-regulates endothelial nitric oxide synthase (eNOS) expression via activation of Rho. Statins are effective in patients with acute coronary syndromes. ⋯ Simvastatin (10 micromol/L) and cerivastatin (10 micromol/L) significantly decreased thrombin-induced membrane translocation of Rho A. Therefore, statins blunt thrombin-induced down-regulation of eNOS expression in human endothelial cells. This finding provides a novel mechanism of the pleiotropic effects of statins, which may be beneficial for patients with acute coronary syndromes.
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J. Cardiovasc. Pharmacol. · May 2006
Nicorandil but not ISDN upregulates endothelial nitric oxide synthase expression, preventing left ventricular remodeling and degradation of cardiac function in Dahl salt-sensitive hypertensive rats with congestive heart failure.
Cardiac endothelial nitric oxide synthase (ecNOS) was suppressed and inducible NOS (iNOS) enhanced at the decompensated heart failure stage in 18-week-old Dahl salt-sensitive (DS) hypertensive rats to which a high-salt diet had been administered from the age of 6 weeks. Nicorandil (NIC) enhanced ecNOS by activating Adenosine triphosphate-sensitive potassium channels (K-ATP channels) in the normal rat left ventricle. In this study, left ventricular hypertrophy, remodeling, function, cardiac ecNOS, and iNOS were compared between NIC and isosorbide dinitrate (ISDN) treatments in DS hypertensive rats with congestive heart failure. ⋯ However, no intragroup differences in iNOS mRNA or protein levels were observed for the 3 groups. More significant improvements in cardiac function and LV hypertrophy regression were observed in an NIC group than in an ISDN group of DS hypertensive rats. Activation of the K-ATP channel seems to induce this beneficial effect, which may be mediated in part by enhanced ecNOS expression in the heart in DS hypertensive congestive heart failure rat model.