title: Angiotensin (1-7) re-establishes impulse conduction in cardiac muscle during ischaemia-reperfusion. The role of the sodium pump.
abstract: BACKGROUND
  The effect of angiotensin (1-7) (Ang 1-7) on membrane potential and excitability of rat heart muscle under ischaemia/reperfusion was investigated.
  
  
  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 degrees 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 voltage-clamped at -40 mV and the current generated by the pump was recorded before and after the administration of Ang (1-7) (10-8 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).
authors.affiliation: Department of Pharmacology, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936-5067, USA. wmello@rcm.upr.edu
authors.forename: Walmor C
authors.initials: WC
authors.lastname: De Mello
mesh_terms: D000803:Angiotensin I; D000818:Animals; D004553:Electric Conductivity; D005260:Female; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D009431:Neural Conduction / Q000187:drug effects*; D010210:Papillary Muscles / Q000294:innervation*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments; D051381:Rats; D017207:Rats, Sprague-Dawley; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D000803:Angiotensin I; D000254:Sodium-Potassium-Exchanging ATPase; C118790:angiotensin I (1-7)