Volume 2, Number 2, June 2001

Enhanced regional AT₂-receptor and PKC_ε expression during cardioprotection induced by AT₁-receptor blockade after reperfused myocardial infarction
Bodh I Jugdutt, Mohammed Balghith

We assessed the effects of the angiotensin II (Ang II) type 1 receptor (AT₁-receptor) blocker, candesartan, (CN, 1 mg/kg i.v. over 30 minutes pre-ischaemia) alone or after intracoronary administration of Ang II type 2 receptor (AT₂-receptor) blocker (PD 123319), protein kinase C (PKC) inhibitor (chelerythrine), endothelial nitric oxide (NO) synthase inhibitor (N^G-monomethyl-L-arginine or L-NMMA), and bradykinin (BK) -B₂ receptor inhibitor (HOE140) on in vivo left ventricular (LV) function and remodelling (echocardiograms/ Doppler) and haemodynamics in 30 dogs with reperfused anterior infarction (90 minutes ischaemia, 120 minutes reperfusion), and ex vivo infarct size, AT₁-receptor/AT₂-receptor proteins and PKC_ε (immunoblots), and cyclic guanosine 3', 5' monophosphate (cGMP, immunoassay). Compared with controls, CN inhibited the Ang II pressor response, reduced LV preload, improved LV systolic and diastolic function, limited LV remodelling, decreased infarct size, and increased AT₂-receptor and PKC_ε proteins in the infarct zone (IZ), and these responses were abrogated by PD 123319, chelerythrine, L-NMMA and HOE140. In addition, the increase in LV cGMP with CN was attenuated by PD 123319, L-NMMA and HOE140. The overall results suggest that AT₂-receptor activation and signalling via BK, PKC_ε and cGMP contribute to cardioprotection associated with AT₁-receptor blockade during ischaemia-reperfusion injury.

JRAAS 2001;2:134-140.

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