Chronic low-dose L-NAME treatment increases nitric oxide production and vasorelaxation in normotensive rats

Physiol Res. 2007:56 Suppl 2:S17-S24. doi: 10.33549/physiolres.931393. Epub 2007 Sep 5.

Abstract

N(G)-nitro-L-arginine methyl ester (L-NAME) is a non-specific nitric oxide (NO) synthase inhibitor, commonly used for the induction of NO-deficient hypertension. The aim of this study was to investigate the effect of chronic low-dose administration of L-NAME on NO production, vascular function and structure of the heart and selected arteries of rats. Adult male Wistar rats were treated with L-NAME in the dose of approximately 1.5 mg/kg/day in drinking water for 8 weeks. Basal blood pressure (BP) of rats (determined by tail-cuff) was 112+/-3 mm Hg. The low-dose administration of L-NAME significantly elevated BP measured on the third and sixth week of treatment vs. controls by approximately 9 % and 12 %, respectively. After this period, BP of L-NAME-treated rats returned to the control values. The relative left ventricular mass, heart fibrosis and collagen III/collagen I ratio were not affected by L-NAME. Similarly, there were no alterations in the cross-sectional area and wall thickness/diameter ratio of the aorta and the femoral artery of L-NAME-treated rats. NO synthase activity (determined by conversion of [(3)H]-L-arginine to [(3)H]-L-citrulline) was not altered in the hypothalamus of L-NAME-treated rats. Interestingly, chronic low-dose L-NAME treatment significantly elevated NO synthase activity in the left ventricle and aorta, increased endothelium-dependent acetylcholine-induced vasorelaxation and reduced serotonin-induced vasoconstriction of the femoral artery. The data suggest that chronic low-dose L-NAME treatment can increase NO production and vasorelaxation in normotensive rats without negative structural changes in the cardiovascular system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Administration, Oral
  • Animals
  • Aorta / drug effects
  • Aorta / enzymology
  • Blood Pressure / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology*
  • Femoral Artery / drug effects
  • Heart Ventricles / drug effects
  • Heart Ventricles / enzymology
  • Hypothalamus / drug effects
  • Hypothalamus / enzymology
  • Male
  • NG-Nitroarginine Methyl Ester / administration & dosage
  • NG-Nitroarginine Methyl Ester / pharmacology*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase / metabolism
  • Rats
  • Rats, Wistar
  • Serotonin / pharmacology
  • Time Factors
  • Up-Regulation
  • Vasoconstrictor Agents / pharmacology
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology

Substances

  • Enzyme Inhibitors
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Nitric Oxide
  • Serotonin
  • Nitric Oxide Synthase
  • Acetylcholine
  • NG-Nitroarginine Methyl Ester