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Cardioprotection after angiotensin II type 1 blockade involves angiotensin II type 2 receptor expression and activation of protein kinase C- in acutely reperfused myocardial infarction in the dog

Effect of UP269-6 and losartan on AT1- and AT2-receptor expression and IP3 receptor and PKC proteins

Division of Cardiology, Department of Medicine and the Cardiovascular Research Group, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada

Vijayan Menon

Division of Cardiology, Department of Medicine and the Cardiovascular Research Group, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada

Bodh I Jugdutt

Division of Cardiology, Department of Medicine and the Cardiovascular Research Group, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada, bjugdutt{at}cha.ab.ca

To determine whether cardioprotection after chronic angiotensin II (Ang II) type 1 (AT₁) receptor blockade involves Ang II type 2 (AT₂) receptor expression and protein kinase C- (PKC) activation, we measured in vivo haemodynamics and left ventricular (LV) remodelling and dysfunction (echocardiogram/ Doppler) and ex vivo AT₁/AT₂-receptor expression, IP ₃R (1, 4, 5-inositol trisphosphate type 2 receptor) and PKC proteins in dogs with acutely reperfused (90 minutes ischaemia, 90 minutes reperfusion) myocardial infarction (MI) following seven days of AT₁-receptor blockade with oral losartan or UP269-6. The animals were randomised to sham; sham + losartan or UP269-6; MI alone; MI + losartan; MI + UP269-6. More marked AT₁-receptor blockade with UP269-6 (greater inhibition of Ang II pressor responses) was associated with a smaller increase in preload, less systolic and diastolic dysfunction, less infarct expansion, and smaller LV diastolic and systolic volumes. However, both AT₁-receptor antagonists decreased infarct size. Importantly, MI decreased AT₁-receptor and AT₂-receptor expression while MI after AT₁-receptor antagonism increased AT₁-receptor (mRNA, not protein) and AT ₂-receptor (mRNA and protein) expression as well as IP₃R and PKC proteins and cyclic guanosine 3', 5' monophosphate (cGMP). These results suggest that cardioprotection induced by chronic AT₁-receptor antagonism involves enhanced AT₂-receptor expression and possibly downstream signalling through IP₃R, PKC and cGMP.

Key Words: AT1-receptor • AT2-receptor • mRNA • PKC • IP3R receptor • ischaemia-reperfusion

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 1, No. 2, 184-195 (2000)
DOI: 10.3317/jraas.2000.024


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Yi Xu Articles by Jugdutt, B. I Search for Related Content PubMed PubMed Citation Articles by Yi Xu, Articles by Jugdutt, B. I Social Bookmarking                         What's this?