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

• Published in: Physiological research Vol. 56 Suppl 2; pp. S17 - S24
• Main Authors: Bernátová, I, Kopincová, J, Púzserová, A, Janega, P, Babál, P
• Format: Journal Article
• Language: English
• Published: Czech Republic Institute of Physiology 2007
• Subjects: 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; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; Proteins; Rats; Rats, Wistar; Rodents; Serotonin - pharmacology; Studies; Time Factors; Up-Regulation; Vasoconstrictor Agents - pharmacology; Vasodilation - drug effects; Vasodilator Agents - pharmacology; Veins & arteries
• ISSN: 0862-8408; 1802-9973
• DOI: 10.33549/physiolres.931393

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.