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.
Pechánová
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Institute of Normal and Pathological Physiology Slovak, Academy of Sciences, Bratislava, Slovak Republic.
Bernátová
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D000818:Animals; D001011:Aorta / Q000378:metabolism; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D004791:Enzyme Inhibitors; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester