Angiotensin (1-7) re-establishes impulse conduction in cardiac muscle during ischaemia-reperfusion. The role of the sodium pump

Abstract

Introduction

The effect of angiotensin (1-7) (Ang 1-7) on membrane potential and excitability of rat heart muscle under ischaemia/reperfusion was investigated.

Materials and methods

The hearts of adult rats were removed under deep anaesthesia and perfused using the Langendorff method. After 40 minutes of global no-flow ischaemia, the heart was reperfused for five minutes and the right ventricle was dissected out and transferred to a transparent chamber, through which normal oxygenated Krebs solution flowed continuously (37°C). Measurements of membrane potential were performed using an intracellular microelectrode connected to a high impedance preamplifier. The muscle was stimulated with rectangular current pulses (3 ms duration; 0.6 Hz) generated by an electronic stimulator and isolation unit. To study the influence of Ang (1-7) on sodium pump current, isolated myocytes were voltageclamped at -40 mV and the current generated by the pump was recorded before and after the administration of Ang (1-7) (10 M)to the bath.

Results

Ang (1-7) (10^-8 M) hyperpolarised the ischaemic heart fibre and re-established impulse propagation. The increment of resting potential was related to the activation of the sodium pump. Indeed, Ang (1-7) (10^-8 M) enhanced the transient outward current generated by an electrogenic sodium pump. Both effects of Ang (1-7) on membrane potential and pump current were abolished by ouabain (10^-7 M). The cardiac refractoriness was also increased by Ang (1-7) (10^-8 M).

Conclusions

Ang (1-7) activates the sodium pump, hyperpolarises the heart cell and re-establishes the impulse conduction during ischaemia/reperfusion. These effects of Ang (1-7), and the increment of cardiac refractoriness, provide an explanation for the reduced incidence of arrhythmias during ischaemia/reperfusion in the presence of Ang (1-7).

Keywords

myocardial ischaemia reperfusion angiotensin (1-7)refractoriness impulse propagation

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