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Cardioprotection Induced by AT1R Blockade After Reperfused Myocardial Infarction: Association With Regional Increase in AT2R, IP3R and PKC Proteins and cGMP

From the Cardiology Division of the Department of Medicine. University of Alberta, Edmonton, Alberta, Canada

Yi Xu

From the Cardiology Division of the Department of Medicine. University of Alberta, Edmonton, Alberta, Canada

Mohammad Balghith

From the Cardiology Division of the Department of Medicine. University of Alberta, Edmonton, Alberta, Canada

Rohit Moudgil

From the Cardiology Division of the Department of Medicine. University of Alberta, Edmonton, Alberta, Canada

Vijayan Menon

From the Cardiology Division of the Department of Medicine. University of Alberta, Edmonton, Alberta, Canada

Background: We hypothesized that the cardioprotective effect of angiotensin II (AngII) type 1 receptor (AT,R) blockade during in vivo ischemia-reperfusion (IR) might be associated with an increase in AngII type 2 receptor (AT₂R) protein, as well as 1,4,5-inositol trisphosphate type 2 receptor (IP₃R) and protein kinase C, (PKC) proteins and cyclic guanosine 3',5' monophosphate (cGMP).

Methods and Results: We studied the effects of the AT₁R blocker, candesartan, on in vivo left ventricular (LV) systolic and diastolic function and remodeling (echocardiogram/Doppler) and hemodynamics during canine reperfused anterior infarction (90-minute ischemia, 120-minute reperfusion), and ex vivo infarct size and AT₁R/AT₂R, IP₃R, and PKC proteins (immunoblots), and cGMP (enzyme immunoassay). Compared with controls, candesartan (1 mg/kg intravenously over 30-minute preischemia) inhibited the AngII pressor response, decreased preload and afterload, improved LV systolic and diastolic function, limited LV remodeling, decreased infarct size (55% vs 27% risk; P < .000003), markedly increased AT₂R, IP₃R, and PKC proteins in the infarct zone, but not the AT,R protein, and increased infarct more than noninfarct cGMP.

Conclusions: The overall results suggest that cardioprotective effects of AT₁R blockade on acute IR injury might involve AT₂R activation and downstream signaling via IP₃R, PKC, and cGMP.

Key Words: candesartan • ventricular function • remodeling • ischemia-reperfusion.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 5, No. 4, 301-311 (2000)
DOI: 10.1054/JCPT.2000.19245


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				B. I Jugdutt, Yi Xu, M. Balghith, and V. Menon Cardioprotective effects of angiotensin II type 1 receptor blockade with candesartan after reperfused myocardial infarction: role of angiotensin II type 2 receptor Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1_suppl): S162 - S166. [Abstract] [PDF]