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Various inotropic effects of angiotensin II in post-ischaemic rat hearts depending on ischaemic time with possible involvement of protein kinase C

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Abstract:

Abstract Aims: 

The present study investigated if the inotropic effect of angiotensin II (AngII) is altered during post-ischaemic reperfusion in hearts subjected to mild and severe ischaemia. The possible involvement of protein kinase C (PKC) in the change in the inotropic effect was also investigated. Methods: 

Isolated Langendorff-perfused rat hearts were perfused under constant flow with oxygenated Krebs–Henseleit buffer and paced at 360 beats min−1. A saline-filled balloon catheter inserted into the left ventricle was used for measurement of contractile force. In the first series of experiments, hearts were subjected to continuous perfusion, 15- or 25-min global ischaemia followed by 45-min reperfusion. At the end of reperfusion, 0.1 mol L−1 AngII was infused for 5 min. In a second series of experiments, AngII was infused in hearts subjected to 25-min ischaemia followed by 45-min reperfusion in the absence or presence of the PKC inhibitor chelerythrine chloride (5 mol L−1). Results: 

The current study demonstrates that AngII exerts a positive inotropic effect in normoxic hearts with an increase of left ventricular developed pressure (LVDP) by 11% (P < 0.05 vs. prior to AngII infusion). In post-ischaemic hearts subjected to 15-min ischaemia no effect of AngII was observed. In hearts subjected to 25 min of ischaemia, however, AngII evoked a negative inotropic response with a decrease of LVDP by 18% (P < 0.05 vs. prior to AngII infusion). The negative inotropic effect of AngII was inhibited by the PKC inhibitor chelerythrine chloride. Conclusions: 

AngII exerts negative inotropic effect in severely injured post-ischaemic heart, possibly through the PKC pathway.

Keywords: angiotensin; heart; inotropy; ischaemia; rat

Document Type: Research Article

DOI: https://doi.org/10.1046/j.1365-201X.2003.01143.x

Affiliations: Department of Integrative Pharmacology, Astrazeneca R & D Mölndal, Mölndal, Sweden

Publication date: 2003-07-01

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