Chronic treatment with an ACE inhibitor, temocapril, lowers the threshold for the infarct size-limiting effect of ischemic preconditioning.
This study examined whether chronic inhibition of the angiotensin-converting enzyme (ACE) lowers the threshold of preconditioning (PC) and potentiates cardio-protection of subthreshold PC. Rabbits were orally administered either 0.5 mg/kg/day temocapril or placebo for 14 days and were randomly subjected to subthreshold PC (i.e., PC with 2 minutes ischemia/5 minutes reperfusion) or no PC before a 30-minute coronary artery occlusion and a 3-hour reperfusion. The size of the infarct was determined by tetrazolium staining and was expressed as the percent of the area at risk (%IS/AR). At the end of the experiment, the lungs were sampled for a tissue ACE activity assay. There was no significant difference in %IS/AR among the rabbits given placebo alone, placebo plus 2 minutes PC, and temocapril alone (%IS/AR = 59.5 +/- 5.8%, 43.6 +/- 3.7%, and 56.7 +/- 7.1%, respectively). However, %IS/AR was significantly reduced in the group that received temocapril and 2 minutes PC before infarction (%IS/AR = 35.4 +/- 4.8%, P < 0.05 vs. placebo control and temocapril control). The lung tissue ACE activity did not differ in the placebo-treated rabbits with and without PC (12.6 +/- 2.8 vs. 13.7 +/- 2.0 nmol/g protein/min) but was suppressed in temocapril-treated rabbits despite 2 minutes PC (0.9 +/- 0.1 vs. 1.5 +/- 0.2 nmol/g protein/min, both P < 0.05 vs. placebo-treated groups). The present results suggest that chronic inhibition of ACE is beneficial for potentiating the anti-infarct effect of subthreshold PC.
Nozawa
Y
Y
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Miura
T
T
Tsuchida
A
A
Kita
H
H
Fukuma
T
T
Shimamoto
K
K
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D008168:Lung / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D011817:Rabbits; D016037:Single-Blind Method; D013841:Thiazepines / Q000627:therapeutic use*; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D013841:Thiazepines; C055603:temocapril hydrochloride