EFFECT OF LONG-TERM NO SYNTHASE INHIBITION ON CYCLIC-NUCLEOTIDE CONTENT IN RAT-TISSUES

The effect of 4 weeks' inhibition of NO synthase by nitro-L-arginine m ethyl ester (L-NAME) on haemodynamic parameters and cGMP and cAMP cont ent was studied in rat tissues L-NAME in both 20 mg/kg/day and 40 mg/k g/day doses significantly increased systolic blood pressure by 28 % an d 30 % and decreased the heart rate by 14 % and 23 %, respectively, af ter the first week. These changes persisted during the following three weeks Left ventricular weight/body weight (LVW/BW) ratio was signific antly elevated in both L-NAME-treated groups by 19 % and 29 %, respect ively. Radioimmunoassay was used to determine the cGMP and cAMP conten t. Cyclic GMP content in animals treated by L-NAME (20 mg/kg/day and 4 0 mg/kg/day) decreased significantly by 13 % and 22 % in the left vent ricle, by 28 % and 62 % in the aorta, by 20 % and 34 % in the brain, a nd by 10 % and 15 % in the kidney, respectively. On the other hand, th e cAMP content increased in both L-NAME treated groups by 8 % and 9 % in the left ventricle, by 28 % and 46 % in the aorta, and by 23 % and 32 % in the brain, respectively. There were no significant changes in kidney cAMP content as compared to control animals The results suggest a simultaneous decrease of cGMP and increase of cAMP content in the m ajority of studied tissues during NO-deficient hypertension.