Long-Acting Ca 2+ Blockers Prevent Myocardial Remodeling Induced by Chronic NO Inhibition in Rats

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Abstract
Chronic inhibition of nitric oxide (NO) synthesis induces cardiac remodeling independent of systemic hemodynamic changes in rats. We examined whether long-acting dihydropyridine calcium channel blockers block myocardial remodeling and whether the activation of 70-kDa S6 kinase (p70S6K) and extracellular signal-regulated kinase (ERK) are involved. Ten groups of Wistar-Kyoto rats underwent 8 weeks of drug treatment consisting of a combination of NO synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME), an inactive isomer (D-NAME), amlodipine (1 or 3 mg/kg per day), or benidipine (3 or 10 mg/kg per day). In other groups, L-NAME was also used in combination with a p70S6K inhibitor (rapamycin), a MEK inhibitor (PD98059), and hydralazine. Systolic blood pressure (SBP), heart rate, and left ventricular weight (LVW) were measured, together with histological examinations and kinase assay. L-NAME increased SBP and LVW (1048±22 versus 780±18 mg, P<0.01) compared with the control, showing a significant increas...

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