This Article Free Full Text (Free PDF) Free References 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 HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by De Mello, W. C Search for Related Content PubMed PubMed Citation Articles by De Mello, W. C Social Bookmarking                   What's this?

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

Department of Pharmacology, Medical Sciences Campus, UPR San Juan, USA, wmello{at}rcm.upr.edu

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

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).

Key Words: myocardial • ischaemia • reperfusion • angiotensin (1-7) • refractoriness impulse propagation

Journal of Renin-Angiotensin-Aldosterone System, Vol. 5, No. 4, 203-208 (2004)
DOI: 10.3317/jraas.2004.041


CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. J. Trask, D. B. Averill, D. Ganten, M. C. Chappell, and C. M. Ferrario Primary role of angiotensin-converting enzyme-2 in cardiac production of angiotensin-(1-7) in transgenic Ren-2 hypertensive rats Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H3019 - H3024. [Abstract] [Full Text] [PDF]

				R. A.S. Santos, C. H. Castro, E. Gava, S. V.B. Pinheiro, A. P. Almeida, R. D. de Paula, J. S. Cruz, A. S. Ramos, K. T. Rosa, M. C. Irigoyen, et al. Impairment of In Vitro and In Vivo Heart Function in Angiotensin-(1-7) Receptor Mas Knockout Mice Hypertension, May 1, 2006; 47(5): 996 - 1002. [Abstract] [Full Text] [PDF]

				C. M. Ferrario, A. J. Trask, and J. A. Jessup Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1-7) in regulation of cardiovascular function Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2281 - H2290. [Abstract] [Full Text] [PDF]