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-con verting enzyme inhibitor captopril on cGMP and cAMP concentration in the le ft ventricle and aorta after NO synthase inhibition by 4-week-lasting N-G-n itro-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 compl etely prevented L-NAME-induced hypertension and LV hypertrophy development. Compared to the controls. cGMP concentration in the L-NAME 20 and L-NAME 4 0 groups was decreased by 13 % and 22 %, respectively, in the left ventricl e and by 27 % and 56 % hin the aorta, respectively. Captopril did not influ ence this decrease of cGMP concentration. Cyclic AMP concentration in the a orta of L-NAME 20 group increased by 17 %. In the L-NAME 40 group cAMP conc entration increased by 17% in the left ventricle and by 34 % in the aorta c ompared to controls. This increase was enhanced in rats given L-NAME togeth er 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.