Cardioprotective effect of the angiotensin II type 1 receptor antagonist TCV-116 on ischemia-reperfusion injury.
We investigated the protective effect of angiotensin II (Ang II) type 1 receptor antagonist on myocardial ischemia-reperfusion injury and the role of exogenous Ang II to this injury in perfused hearts. We orally administered TCV-116 (Ang II type 1 receptor antagonist) and delapril (angiotensin converting enzyme inhibitor) to Wistar rats for 1 week and measured the immunoreactive cardiac Ang II. Immunoreactive cardiac Ang II (pg/gm tissue) was 14.3 +/- 2.0 in control group, 11.8 +/- 0.8 in TCV-116-treated group, and 7.3 +/- 0.6 in delapril-treated group (p < 0.05 compared to TCV-116-treated group; p < 0.01 compared to control group). The 15 hearts (five rats in each group) were perfused by a langendorff method and global ischemia was maintained for 30 min. Both TCV-116 and delapril were found to improve postischemic cardiac function and decrease reperfusion creatine kinase (CK) release. Ang II injection before ischemia worsened postischemic cardiac function and increased reperfusion CK release. Only TCV-116 prevented this injury. These data indicated that TCV-116 Ang II type 1 receptor antagonist was effective against myocardial ischemia-reperfusion injury, and exogenous Ang II accelerated this injury through Ang II type 1 receptor.
Yoshiyama
M
M
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Kim
S
S
Yamagishi
H
H
Omura
T
T
Tani
T
T
Yanagi
S
S
Toda
I
I
Teragaki
M
M
Akioka
K
K
Takeuchi
K
K
D000804:Angiotensin II / Q000032:analysis / Q000037:antagonists & inhibitors / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003402:Creatine Kinase / Q000032:analysis; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000737:chemistry; D007189:Indans / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles; D017725:Ventricular Pressure / Q000187:drug effects / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007189:Indans; D013777:Tetrazoles; D000804:Angiotensin II; D003402:Creatine Kinase; C077793:candesartan cilexetil; C047759:delapril