Aims: 

N^G-Nitro-L-arginine methyl ester (L-NAME) is a non-specific nitric oxide (NO) synthase inhibitor, commonly used for the development 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.

Methods: 

Adult male Wistar rats were treated with L-NAME in the dose of 1.5 mg/kg/ day in drinking water for 8 weeks.

Results: 

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 [³H]-L-arginine to [³H]-L-citrulline) was significantly elevated in the left ventricle and aorta of L-NAME treated rats by approximately 45 and 43%, respectively. Endothelium-dependent acetylcholine-induced vasorelaxation of the femoral artery (determined using wire myograph) was significantly increased and serotonin-induced vasoconstriction was reduced.

Conclusion: 

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.

This study was supported by APVT-51-018004 and VEGA 2/7064/27.