ACE inhibitors and cardiac ACE mRNA in volume overload-induced cardiac hypertrophy.
Quinapril, an angiotensin-converting enzyme (ACE) inhibitor with high affinity for cardiac ACE, prevents increases in both plasma and cardiac angiotensin II (ANG II) and development of cardiac hypertrophy after aortocaval shunt in rats. In contrast, enalapril, an ACE inhibitor with low affinity for cardiac ACE, only prevents the increase in plasma ANG II. In the present study, we assessed whether these differences between enalapril and quinapril reflect different inhibition of cardiac tissue ACE and local ANG II by measuring their effects on cardiac ACE mRNA. Treatment with enalapril (250 mg/l) and quinapril (200 mg/l in drinking water) was started 3 days before the shunt and sham surgery. After 1 wk of aortocaval shunt, the hearts were excised and the left ventricle and right ventricle were weighed and used for reverse transcriptase-polymerase chain reaction (RT-PCR) assays for ACE and phosphoglycerate kinase-1 (internal standard). Quinapril, but not enalapril, inhibited the development of cardiac hypertrophy by aortocaval shunt. The shunt increased ACE mRNA in both left and right ventricles about twofold. In animals with aortocaval shunt, quinapril markedly further upregulated ACE mRNA in both ventricles, whereas enalapril did not cause significant changes. In sham rats, both ACE inhibitors increased ACE mRNA, but the increase was more pronounced by treatment with quinapril. These studies show that in vivo ACE inhibitors with low (enalapril) vs. high (quinapril) affinity for cardiac ACE differ in their effects on cardiac ACE mRNA. This difference is more pronounced in volume overload-induced cardiac hypertrophy, presumably reflecting their different effects on cardiac ANG II.
Lear
W
W
Hypertension Unit, University of Ottawa Heart Institute, Ontario, Canada.
Ruzicka
M
M
Leenen
F H
FH
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D004656:Enalapril / Q000494:pharmacology; D006352:Heart Ventricles; D006940:Hyperemia / Q000150:complications*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D000077583:Quinapril; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D012333:RNA, Messenger; D044005:Tetrahydroisoquinolines; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A; D000077583:Quinapril