Cardioprotective effect of orally administered angiotensin-converting enzyme inhibitor against ischemia. Reperfusion injury in the isolated rat heart.
Angiotensin-converting enzyme inhibitors are reported to be cardioprotective against ischemia/reperfusion injury. Few studies have been made, however, on the cardioprotectiveness of orally administered angiotensin-conrerting enzyne inhibitors. Wistar rats were pretreated with oral delapril--30 mg/kg/day in the low-dose group and 90 mg/kg/day in the high-dose group--for one week. Cardiac function recovery was assessed after ischemia/reperfusion in the isolated working heart model. Rat hearts in the high-dose group were also reperfused with a solution containing nitro-L-arginine methyl ester, a nitric-oxide synthase inhibitor. Oral pretreatment of delapril did not affect baseline cardiac function. The percentage of cardiac output recovery for controls was 22 +/- 4.5%, for the low-dose group 44 +/- 6.5% (P < 0.05 versus controls), and for the high-dose group 76 +/- 5.3% (P < 0.001 versus controls and low-dose). Although coronary vascular resistance at the end of reperfusion showed no difference, mean coronary vascular resistance early after reperfusion was significantly lower (P < 0.0001) in both delapril groups than in control. In the high-dose group, reperfusion with L-NAME significantly increased coronary vascular resistance after ischemia/reperfusion and attenuated the cardioprotectiveness of delapril (P < 0.05 versus without nitro-L-arginine methyl ester). We thus found that oral administration of delapril was cardioprotective dose-dependently against ischemia/reperfusion injury. Nitric oxide appeared to be involved in the mechanism behind this cardioprotective effect.
Hata
M
M
Department of Thoracic and Cardiovascular Surgery, Tohoku University School of Medicine, Sendai, Japan.
Iguchi
A
A
Li
Y
Y
Watanabe
S
S
Kamada
M
M
Ohmi
M
M
Tabayashi
K
K
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007189:Indans / Q000008:administration & dosage*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D007189:Indans; D019331:NG-Nitroarginine Methyl Ester; C047759:delapril