Role of the angiotensin II type 1 receptor in preconditioning against infarction.
OBJECTIVE
To assess the role of angiotensin II type 1 (AT1) receptor in the mechanism of limitation of infarct size by preconditioning.


METHODS
Myocardial infarction was induced by 30 min coronary artery occlusion and 3 h reperfusion in the rabbit. The infarct size was determined by tetrazolium staining and expressed as a percentage of the area at risk (%ISAR). Rabbits were subjected to one of the following four treatments: no drug (i.e. control); administration of 1 mg/kg CV-11,974, a specific AT1 receptor antagonist, 20 min before ischemia; preconditioning with 5 min ischemia and then 5 min reperfusion; and administration of CV-11,974 plus preconditioning.


RESULTS
It was confirmed that the same dose of CV-11,974 (i.e. 1 mg/kg) could block the pressor response to injection of 0.5 microgram/kg angiotensin II completely for 60 min. The %ISAR for the untreated control group was 45.1 +/- 3.9%, and administration of CV-11,974 alone did not modify the %ISAR (47.5 +/- 5.9%). The %ISAR for the group administered both CV-11,974 and subjected to preconditioning (30.4 +/- 3.5%) was modestly smaller than that for the controls, but was significantly larger than for the preconditioned group (12.0 +/- 1.8%). The angiotensin II level in arterial plasma did not differ before and after the 5 min preconditioning. It was shown with separate groups of rabbits that a modest protection conferred by preconditioning with 3 min ischemia was also attenuated by administration of CV-11,974 (%ISAR 28.4 +/- 4.3 with CV-11,974 versus 19.3 +/- 1.7% without CV-11,974, P < 0.05).


CONCLUSIONS
These results suggest that activation of AT1 receptors by angiotensin II produced locally in the heart contributes to the limitation of infarct size by preconditioning.
Nakano
A
A
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Miura
T
T
Ura
N
N
Suzuki
K
K
Shimamoto
K
K
D000804:Angiotensin II / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000503:physiopathology*; D011817:Rabbits; D011863:Radioimmunoassay; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C081643:candesartan