Mechanism of Structural Remodelling of the Rat Aorta During Long-Term N^G-Nitro-_L-arginine Methyl Ester Treatment

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The aim of the present study was to determine whether decreased nitric oxide (NO) synthase production or rather NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension was responsible for metabolic and structural remodelling of the rat aorta during four-week L-NAME treatment. Three groups of male Wistar rats were investigated: control, treated with 20 mg/kg per day L-NAME (L-NAME20), and treated with 40 mg/kg per day L-NAME (L-NAME40). Systolic blood pressure significantly increased in L-NAME20 to 146% and in L-NAME40 to 149% of the control value. NO synthase activity in the aorta significantly decreased in L-NAME20 and L-NAME40 to 86% and 65% of the control values, respectively. Proteosynthesis was significantly elevated in both L-NAME groups, while nuclear DNA concentration was significantly elevated only in the L-NAME40 group. Cyclic GMP concentration significantly decreased in L-NAME20 to 73% and in L-NAME40 to 46% of the control. Cyclic AMP concentration significantly increased in L-NAME20 and L-NAME40 to 128% and 145% of the control value, respectively. The diameter and wall thickness-to-diameter ratio were significantly elevated only in the L-NAME40 group. We conclude that remodelling of the aorta in L-NAME-treated rats was rather associated with NO deficiency than L-NAME-induced hypertension.
公益社団法人日本薬理学会の論文
1999-09-00