ACE-INHIBITORS AND CARDIAC ACE MESSENGER-RNA 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 cardia c angiotensin II (ANG II) and development of cardiac hypertrophy after aortocaval shunt in rats. In contrast, enalapril, an ACE inhibitor wi th low affinity for cardiac ACE, only prevents the increase in plasma ANG II. In the present study, we assessed whether these differences be tween 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 d rinking water) was started 3 days before the shunt and sham surgery. A fter 1 wk of aortocaval shunt, the hearts were excised and the left ve ntricle and right ventricle were weighed and used for reverse transcri ptase-polymerase chain reaction (RT-PCR) assays for ACE and phosphogly cerate kinase-l (internal standard). Quinapril, but not enalapril, inh ibited the development of cardiac hypertrophy by aortocaval shunt. The shunt increased ACE mRNA in both left and right ventricles about twof old. In animals with aortocaval shunt, quinapril markedly further upre gulated ACE mRNA in both ventricles, whereas enalapril did not cause s ignificant changes. In sham rats, both ACE inhibitors increased ACE mR NA, 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 overlo ad-induced cardiac hypertrophy, presumably reflecting their different effects on cardiac ANG II.