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 S ，Satoh K ，Kaneta S ，Ichihara K ... -  《-》

Cardioprotective effects of angiotensin II type 1 receptor blockade with olmesartan on reperfusion injury in a rat myocardial ischemia-reperfusion model.

Dai W ，Hale SL ，Kay GL ，Jyrala AJ ，Kloner RA ... -  《-》

Angiotensin II receptor blocker inhibits tumour necrosis factor-alpha-induced cell damage in human renal proximal tubular epithelial cells.

Kagawa T ，Takao T ，Horino T ，Matsumoto R ，Inoue K ，Morita T ，Hashimoto K ... -  《-》

Effects of captopril and angiotensin II receptor blockers (AT1, AT2) on myocardial ischemia-reperfusion induced infarct size.

The renin-angiotensin system (RAS) plays a major role in regulating the cardiovascular system, and disorders of the RAS contribute largely to the cardiac pathophysiology, including myocardial ischemia-reperfusion (MI/R) injury. Two subtypes of angiotensin II (Ang II) receptors have been defined on the basis of their differential pharmacological properties. The current study was undertaken to address the question as to whether the inhibition of the angiotensin converting enzyme (ACE) by captopril and the AT1 and AT2 receptor blockers losartan and PD123319 modulate MI/R-induced infarct size in an in vivo rat model. To produce necrosis, a branch of the descending left coronary artery was occluded for 30 min followed by two hours of reperfusion. ECG changes, blood pressure, and heart rate were measured during the experiment. Captopril (3 mg/kg), losartan (2 mg/kg), and PD123319 (20 μg/kg/min) were given in an IV 10 min before ischemia and were continued during the ischemic period. The infarcted area was measured by TTC staining. The volume of infarct and the risk zone was determined by planimetry. Compared to the control group (55.62±4.00%) both captopril and losartan significantly reduced the myocardial infarct size (30.50±3.26% and 37.75±4.44%), whereas neither PD123319 nor PD123319+losartan affected the infarct size volume (46.50±3.72% and 54.62±2.43%). Our data indicates that captopril and losartan exert cardioprotective activity after an MI/R injury. Also, infarct size reduction by losartan was halted by a blockade of the AT2 receptor. Therefore, the activation of AT2 receptors may be potentially protective and appear to oppose the effects mediated by the AT1 receptors.

Parlakpinar H ，Ozer MK ，Acet A 《-》

Role of angiotensin II type-1 and type-2 receptors on vascular smooth muscle cell growth and glucose metabolism in diabetic rats.

Igarashi M ，Hirata A ，Nozaki H ，Kadomoto-Antsuki Y ，Tominaga M ... -  《DIABETES RESEARCH AND CLINICAL PRACTICE》