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

DOI Web Site 被引用文献1件
  • Bodh I. Jugdutt
    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

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<jats:p> 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 (AT<jats:sub>2</jats:sub>R) protein, as well as 1,4,5-inositol trisphosphate type 2 receptor (IP<jats:sub>3</jats:sub>R) and protein kinase C <jats:sub>ε</jats:sub>, (PKC<jats:sub>ε</jats:sub>) proteins and cyclic guanosine 3',5' monophosphate (cGMP). </jats:p><jats:p> Methods and Results: We studied the effects of the AT<jats:sub>1</jats:sub>R 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 AT<jats:sub>1</jats:sub>R/AT<jats:sub>2</jats:sub>R, IP<jats:sub>3</jats:sub>R, and PKC<jats:sub>ε</jats:sub> 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 AT<jats:sub>2</jats:sub>R, IP<jats:sub>3</jats:sub>R, and PKC<jats:sub>ε</jats:sub> proteins in the infarct zone, but not the AT,R protein, and increased infarct more than noninfarct cGMP. </jats:p><jats:p> Conclusions: The overall results suggest that cardioprotective effects of AT<jats:sub>1</jats:sub>R blockade on acute IR injury might involve AT<jats:sub>2</jats:sub>R activation and downstream signaling via IP<jats:sub>3</jats:sub>R, PKC<jats:sub>ε</jats:sub>, and cGMP. </jats:p>

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