Improvement of stunned myocardium in dogs with olmesartan, an angiotensin II type 1 receptor antagonist, is independent of type 2 receptors.
Olmesartan is a selective angiotensin II type 1 receptor (AT1) antagonist. In pentobarbital-anesthetized open-chest dogs, ischemia/reperfusion was induced by ligating the left anterior descending coronary artery for 20 min and releasing it for 60 min, respectively. The myocardial contraction in the ischemic area decreased and returned towards its pre-ischemic level during reperfusion but incompletely. Olmesartan improved the recovery of myocardial contraction during reperfusion associated with restoration of myocardial ATP. Angiotensin II repelled by AT1 receptors occupied by olmesartan can reach and stimulate the angiotensin II type 2 (AT2) receptors, resulting in some beneficial effects on the ischemic myocardium. In fact, AT2 receptor mRNA was found in the adult dog myocardium. In addition, the plasma level of angiotensin II was significantly increased by olmesartan. PD123319, a selective AT2 receptor antagonist, however, did not modify the effect of olmesartan on the cardiac contraction. The hypertensive response to exogenous angiotensin II was completely inhibited by olmesartan, whereas PD123319 did not abolish the effect of olmesartan. In conclusion, olmesartan protects the ischemic/reperfused heart against ischemic injury through inhibition of AT1 receptors but not indirect activation of AT2 receptors.
Kano
Seiichiro
S
Division of Pharmacology, Hokkaido Pharmaceutical University, Otaru, Japan.
Satoh
Kumi
K
Kaneta
Shigeru
S
Ichihara
Kazuo
K
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D017682:Myocardial Stunning / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; C073402:PD 123319; C437965:olmesartan