Cardioprotection after angiotensin II type 1 blockade involves angiotensin II type 2 receptor expression and activation of protein kinase C-ε in acutely reperfused myocardial infarction in the dog
Restricted accessOtherFirst published online June, 2000
Cardioprotection after angiotensin II type 1 blockade involves angiotensin II type 2 receptor expression and activation of protein kinase C-ε in acutely reperfused myocardial infarction in the dog
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-ε (PKCε) 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 PKCε 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 PKCε 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, PKCε and cGMP.
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