Author: Diaz R.J. Wilson G.J.
Publisher: Academic Press
ISSN: 0022-2828
Source: Journal of Molecular and Cellular Cardiology, Vol.29, Iss.1, 1997-01, pp. : 129-139
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Abstract
The aim of the present study was to assess the participation of angiotensin II receptors in the triggering mechanism of ischemic preconditioning. Isolated buffer-perfused rabbit hearts were subjected to 40 min of regional ischemia (37#°C) followed by 60 min of reperfusion. Ischemic preconditioning was induced with three cycles of 5-min ischemia and 10-min reperfusion given prior to the 40-min ischemic period. Infarct size and ventricular function were assessed. Ischemic preconditioning reduced infarct size to 5.2±1.2% of the area at risk (mean± s.e.m. , P <0.001) when compared to controls (26.4±3.0%), but did not protect against ventricular dysfunction. Activation of angiotensin II receptors with angiotensin II (100 n m ) also limited infarct size (9.6±2.2%, P <0.01 v control group). Inhibition of angiotensin II receptors with [Sar 1 , Val 5 , Ala 8 ]-angiotensin II (saralasin, 1 & mu; m ) blocked the protection of ischemic preconditioning against necrosis (29.7±3.2%) while it did not increase infarct size in saralasin-treated control hearts (31.5±3.9%). Furthermore, inhibition of the AT 1 subtype of the angiotensin II receptor with losartan (20 & mu; m ), but not inhibition of the AT 2 subtype with PD-123,319 ditrifluoroacetate (10 & mu; m ), abolished the infarct size-limiting effect of ischemic preconditioning. We conclude that the AT 1 angiotensin II receptor participates in ischemic preconditioning. Thus, in the isolated rabbit heart, activation of AT 1 receptors must occur before prolonged ischemia for ischemic preconditioning to limit infarction.
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