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 methyl ester (L-NAME) on haemodynamic parameters and cGMP and cAMP content was studied in rat tissues. L-NAME in both 20 mg/kg/day and 40 mg/kg/day doses significantly increased systolic blood pressure by 28% and 30% and decreased the heart rate by 14% and 23%, respectively, after the first week. These changes persisted during the following three weeks. Left ventricular weight/body weight (LVW/BW) ratio was significantly elevated in both L-NAME-treated groups by 19% and 29%, respectively. Radioimmunoassay was used to determine the cGMP and cAMP content. Cyclic GMP content in animals treated by L-NAME (20 mg/kg/day and 40 mg/kg/day) decreased significantly by 13% and 22% in the left ventricle, by 28% and 62% in the aorta, by 20% and 34% in the brain, and by 10% and 15% in the kidney, respectively. On the other hand, the 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 majority of studied tissues during NO-deficient hypertension.