Effect of captopril in L-NAME-induced hypertension on the rat myocardium, aorta, brain and kidney.
Long-term administration of NG-nitro-L-arginine methyl ester (L-NAME) induces development of hypertension and hypertrophy of the left ventricle in rats. The aim of the present study was to demonstrate the effect of chronic L-NAME treatment on DNA and RNA concentration, and protein synthesis in the rat heart, aorta, brain and kidney and to determine the effect of angiotensin converting enzyme (ACE) inhibitor captopril on these potential alterations. Four groups of rats were investigated: control, L-NAME (40 mg kg-1 day-1), captopril (100 mg kg-1 day-1), and L-NAME (40 mg kg-1 day-1) + captopril (100 mg kg-1 day-1). NO synthase activity in the heart, aorta, brain and kidney was found to be decreased in the L-NAME group. In the group of rats treated with L-NAME + captopril, captopril did not affect NO synthase inhibition. Captopril, however, completely prevented development of hypertension and left ventricular hypertrophy in this group. In the L-NAME group, DNA and RNA concentrations, as well as [14C]leucine incorporation, were significantly increased in all the tissues investigated. In the L-NAME + captopril group, captopril completely prevented the enhancement of DNA and RNA concentrations and [14C]leucine incorporation in all tissues compared to the L-NAME group. Moreover, a significant decrease in RNA concentration and [14C]leucine incorporation below control values was found in the captopril group as well as the L-NAME + captopril group in all the tissues investigated. We conclude that captopril prevented the development of hypertension and increase in nucleic acid concentration and protein synthesis in the heart, aorta, brain and kidney in rats treated with L-NAME + captopril. However, this protective effect of captopril was not associated with increased NO synthase activity in this model of hypertension.
Bernátová
I
I
Department of Cardiovascular Physiology, Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic. bernat@unpf.savba.sk
Pechánová
O
O
Simko
F
F
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002216:Captopril / Q000494:pharmacology*; D006152:Cyclic GMP / Q000032:analysis; D004247:DNA / Q000032:analysis; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000378:metabolism; D014176:Protein Biosynthesis; D012313:RNA / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D012313:RNA; D004247:DNA; D002216:Captopril; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester