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• W2140466093 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 increase in cross-sectional area of cardiomyocytes after 8 weeks. Amlodipine, benidipine, or hydralazine equally attenuated the increase in SBP induced by L-NAME. However, both amlodipine and benidipine but not hydralazine attenuated the increase in LVW by L-NAME (789+/-27, 825+/-20 mg, P<0.01, and 1118+/-29 mg, NS, respectively), also confirmed by histological analysis. L-NAME caused a 2.2-fold/1.8-fold increase in p70S6K/ERK activity in myocardium compared with the control, both of which were attenuated by both amlodipine and benidipine but not hydralazine. Both rapamycin and PD98059 attenuated cardiac hypertrophy in this model. Thus, long-acting dihydropyridine calcium channel blockers inhibited cardiac hypertrophy induced by chronic inhibition of NO synthesis by inhibiting both p70S6K and ERK in vivo." @default.
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• W2140466093 date "2003-04-01" @default.
• W2140466093 modified "2023-10-03" @default.
• W2140466093 title "Long-Acting Ca ²⁺ Blockers Prevent Myocardial Remodeling Induced by Chronic NO Inhibition in Rats" @default.
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• W2140466093 doi "https://doi.org/10.1161/01.hyp.0000062881.36813.7a" @default.
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