Mechanism of structural remodelling of the rat aorta during long-term NG-nitro-L-arginine methyl ester treatment

Jpn J Pharmacol. 1999 Sep;81(1):99-106. doi: 10.1254/jjp.81.99.

Abstract

The aim of the present study was to determine whether decreased nitric oxide (NO) synthase production or rather N(G)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / anatomy & histology
  • Aorta, Thoracic / drug effects*
  • Aorta, Thoracic / enzymology
  • Aorta, Thoracic / metabolism
  • Blood Pressure / drug effects
  • Carbon Radioisotopes
  • Cyclic AMP / metabolism
  • DNA / metabolism
  • Enzyme Inhibitors / toxicity*
  • Leucine / metabolism
  • Male
  • NG-Nitroarginine Methyl Ester / toxicity*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Rats
  • Rats, Wistar

Substances

  • Carbon Radioisotopes
  • Enzyme Inhibitors
  • Nitric Oxide
  • DNA
  • Cyclic AMP
  • Nitric Oxide Synthase
  • Leucine
  • NG-Nitroarginine Methyl Ester