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Angiotensin (1-7) re-establishes impulse conduction in cardiac muscle during ischaemia-reperfusion. The role of the sodium pump
Walmor C De Mello
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
References
- Donahue M., Hsieh F., Baronas E. et al.A novel angiotensin-converting enzyme related carboxypeptidase (ACE2) converts angiotensin 1 to angiotensin (1-9). Circ Res 2000;87:E1-E9.[Web of Science][Medline]
[Order article via Infotrieve]
- Tipnis SR, Hooper NM, Hyde R. et al.A human homolog of angiotensin converting enzyme. Cloning and functional expression as a captopril insensitive carboxypeptidase. J Biol Chem 2000;275:33238-43.[Abstract/Free Full Text]
- Zisman LS, Keller RS,Weaver B. et al. Increased angiotensin (1-7) forming activity in failing human heart ventricles: evidence for upregulation of the angiotensin converting enzyme homolog,ACE2. Circulation 2003;108:1707-12.[Abstract/Free Full Text]
- Zisman LS ACE2: Its role in the counter regulatory response to heart failure; In: De Mello WC (ed.). Renin Angiotensin System and the Heart. London: John Wiley and Sons, 2004;119-32.
- McMurray J., Davie AP Angiotensin (1-7) attenuates the development of heart failure after myocardial infarction in rats. Circulation 2002;106:e147.[CrossRef][Medline]
[Order article via Infotrieve]
- Ferrario C., Chappell M.,Tallant EK et al. Counter regulatory actions of angiotensin (1-7). Hypertension 1997;30:535-41.[Abstract/Free Full Text]
- Averill DB, Ishiyama Y., Chapell MC, Ferrario CM Cardiac angiotensin (1-7) in ischaemic cardiomyopathy. Circulation 2003;108:2141-6.[Abstract/Free Full Text]
- Loot AE, Rocks AJ, Henning RH et al. Angiotensin (1-7) attenuates the development of heart failure after myocardial infarction in rats. Circulation 2002;105:1548-50.[Abstract/Free Full Text]
- Ferreira AJ, Santos RA, Almeida AP Angiotensin (1-7): cardioprotective effect in myocardial ischaemia/reperfusion. Hypertension 2001;38:665-8.[Abstract/Free Full Text]
- Powell T., Twist T. A rapid technique for the isolation and purification of adult cardiac muscle cells having respiratory control and a tolerance to calcium. Biochem Biophys Res Commun 1976;72:327-33.[Web of Science][Medline]
[Order article via Infotrieve]
- Tanigushi Y., Kokubun S., Noma A., Hirisawa H. Spontaneously active cells isolated from the sinoatrial and atrioventricular node of the rabbit heart. Jpn J Physiol 1981;31: 547-58.[Web of Science][Medline]
[Order article via Infotrieve]
- Isenberg G., KloknerV. Glycocalyx is not required for slow inward current in isolated rat heart myocytes. Nature 1990;284:358-60.[CrossRef]
- Eisner DA, Lederer WJ,Vaughan-Jones RD Electrogenic Na pumping in cardiac muscle; simultaneous measurement of intracellular Na activity, membrane current and tension. J Physiol (London) 1980;300:42P.
- Gadsby DC Activation of electrogenic Na/K exchange by extracellular K in canine cardiac Purkinje fibers. Proc Natl Acad Sci USA 1980;77:4035-9.[Abstract/Free Full Text]
- Gadsby DC, Cranefield PF Direct measurements of changes in sodium pump current in canine Purkinje fibers. Proc Natl Acad Sci USA 1979;76:1783-7.[Abstract/Free Full Text]
- Eisner DC, Lederer WJ Characterisation of the electrogenic sodium pump in cardiac Purkinje fibers. J Physiol (London) 1980;303:441-74.[Abstract/Free Full Text]
- Buhagiar KA, Hansen PS, Gray PF, Mihailidou AS, Rasmussen HH Angiotensin regulates the selectivity of the sodium pump for intracellular Na+. Am J Physiol 1999;277: C461-C468.[Web of Science][Medline]
[Order article via Infotrieve]
- De Mello WC Electrical activity of the heart and angiotensin converting enzyme inhibitors; on the hyperpolarizing action of enalapril. J Human Hypertens 2002:16(suppl 1):S89-S92.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
Journal of Renin-Angiotensin-Aldosterone System, Vol. 5, No. 4,
203-208 (2004)
DOI: 10.3317/jraas.2004.041
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