Effect of captopril on cyclic nucleotide concentrations during long-term NO synthase inhibition.
The aim of the present study was to determine the effect of angiotensin-converting enzyme inhibitor captopril on cGMP and cAMP concentration in the left ventricle and aorta after NO synthase inhibition by 4-week-lasting N(G)-nitro-L-arginine-methyl ester (L-NAME) treatment. Five groups of rats were investigated: controls, L-NAME in the dose 20 mg/kg/day (L-NAME 20), L-NAME in the dose 40 mg/kg/day (L-NAME 40), captopril in the dose 100 mg/kg/day, L-NAME 40 mg/kg/day together with captopril 100 mg/kg/day. Captopril completely prevented L-NAME-induced hypertension and LV hypertrophy development. Compared to the controls, cGMP concentration in the L-NAME 20 and L-NAME 40 groups was decreased by 13% and 22%, respectively, in the left ventricle and by 27% and 56% in the aorta, respectively. Captopril did not influence this decrease of cGMP concentration. Cyclic AMP concentration in the aorta of L-NAME 20 group increased by 17%. In the L-NAME 40 group, cAMP concentration increased by 17% in the left ventricle and by 34% in the aorta compared to controls. This increase was enhanced in rats given L-NAME together with captopril. Captopril alone had no effect on cAMP concentration. We conclude that captopril does not affect the concentration of cGMP, however, it has more than the additive effect on the cAMP concentration increase in the cardiovascular system during long-term NO synthase inhibition.
Pechánová
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O
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic. pechan@unpf.savba.sk
Bernátová
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I
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D002216:Captopril; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester