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Inhibition of the renin-angiotensin system: effects on tachycardia-induced early electrical remodelling in rabbit atrium.
J Renin Angiotensin Aldosterone Syst. 2008 Sep; 9(3):125-32.JR

Abstract

INTRODUCTION

Tachycardia-induced atrial remodelling (as an equivalent to atrial fibrillation) can be influenced by the renin-angiotensin system. Effects of a seven-day enalapril pre-treatment (EPT, 0.16 mg/kg body weight subcutaneously every 24 h) on ionic currents underlying tachycardia-induced early electrical remodelling after 24 h rapid atrial pacing (RAP, 600 beats/min) in rabbit atrium were studied.

MATERIALS AND METHODS

Animals were divided into four groups (n=4 each): control; paced only; enalapril only; and enalapril and paced, respectively. Using patch-clamp technique in whole-cell mode, current densities were measured in isolated atrial myocytes.

RESULTS

EPT nearly doubled L-type calcium current (ICa,L, -7.7+/-0.6 pA/pF [control] vs. f -12.3+/-1.2 pA/pF [enalapril only]). RAP reduced ICa,L to -3.6+/-0.7 pA/pF (paced only). Also after EPT, RAP led to a significant downregulation of ICa,L by 39% (-7.5+/-1.3 pA/pF [paced and enalapril]). RAP decreased transient outward potassium current (Ito, -45%, 51.5+/-3.9 pA/pF [control] vs. 28.5+/-4.5 pA/pF [paced only]). EPT did not alter Ito (44.2+/-8.1 pA/pF [enalapril only]). However, RAP did not affect Ito in enalapril-treated animals and averaged 50.4+/-9.8 pA/pF (paced and enalapril).

CONCLUSIONS

In summary, EPT has several effects on ion channels in rabbit atrium: 1) EPT increases ICa,L current density, but cannot prevent its downregulation due to RAP; 2) EPT has no influence on Ito current density, but can prevent its downregulation due to RAP. Although changes of single ion channels must be interpreted in context of the complex atrial electrophysiology as a whole, our results provide a possible explanation of the in vivo observation that angiotensin-converting enzyme inhibition is mainly beneficial on the early electrical remodelling due to the atrial fibrillation-equivalent RAP.

Authors+Show Affiliations

Department of Cardiology, University of Tübingen, Germany. roman.laszlo@med.uniNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18957382

Citation

Laszlo, Roman, et al. "Inhibition of the Renin-angiotensin System: Effects On Tachycardia-induced Early Electrical Remodelling in Rabbit Atrium." Journal of the Renin-angiotensin-aldosterone System : JRAAS, vol. 9, no. 3, 2008, pp. 125-32.
Laszlo R, Eick C, Rueb N, et al. Inhibition of the renin-angiotensin system: effects on tachycardia-induced early electrical remodelling in rabbit atrium. J Renin Angiotensin Aldosterone Syst. 2008;9(3):125-32.
Laszlo, R., Eick, C., Rueb, N., Weretka, S., Weig, H. J., Schreieck, J., & Bosch, R. F. (2008). Inhibition of the renin-angiotensin system: effects on tachycardia-induced early electrical remodelling in rabbit atrium. Journal of the Renin-angiotensin-aldosterone System : JRAAS, 9(3), 125-32. https://doi.org/10.1177/1470320308095262
Laszlo R, et al. Inhibition of the Renin-angiotensin System: Effects On Tachycardia-induced Early Electrical Remodelling in Rabbit Atrium. J Renin Angiotensin Aldosterone Syst. 2008;9(3):125-32. PubMed PMID: 18957382.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of the renin-angiotensin system: effects on tachycardia-induced early electrical remodelling in rabbit atrium. AU - Laszlo,Roman, AU - Eick,Christian, AU - Rueb,Norman, AU - Weretka,Slawomir, AU - Weig,Hans-Joerg, AU - Schreieck,Juergen, AU - Bosch,Ralph F, PY - 2008/10/30/pubmed PY - 2010/1/14/medline PY - 2008/10/30/entrez SP - 125 EP - 32 JF - Journal of the renin-angiotensin-aldosterone system : JRAAS JO - J Renin Angiotensin Aldosterone Syst VL - 9 IS - 3 N2 - INTRODUCTION: Tachycardia-induced atrial remodelling (as an equivalent to atrial fibrillation) can be influenced by the renin-angiotensin system. Effects of a seven-day enalapril pre-treatment (EPT, 0.16 mg/kg body weight subcutaneously every 24 h) on ionic currents underlying tachycardia-induced early electrical remodelling after 24 h rapid atrial pacing (RAP, 600 beats/min) in rabbit atrium were studied. MATERIALS AND METHODS: Animals were divided into four groups (n=4 each): control; paced only; enalapril only; and enalapril and paced, respectively. Using patch-clamp technique in whole-cell mode, current densities were measured in isolated atrial myocytes. RESULTS: EPT nearly doubled L-type calcium current (ICa,L, -7.7+/-0.6 pA/pF [control] vs. f -12.3+/-1.2 pA/pF [enalapril only]). RAP reduced ICa,L to -3.6+/-0.7 pA/pF (paced only). Also after EPT, RAP led to a significant downregulation of ICa,L by 39% (-7.5+/-1.3 pA/pF [paced and enalapril]). RAP decreased transient outward potassium current (Ito, -45%, 51.5+/-3.9 pA/pF [control] vs. 28.5+/-4.5 pA/pF [paced only]). EPT did not alter Ito (44.2+/-8.1 pA/pF [enalapril only]). However, RAP did not affect Ito in enalapril-treated animals and averaged 50.4+/-9.8 pA/pF (paced and enalapril). CONCLUSIONS: In summary, EPT has several effects on ion channels in rabbit atrium: 1) EPT increases ICa,L current density, but cannot prevent its downregulation due to RAP; 2) EPT has no influence on Ito current density, but can prevent its downregulation due to RAP. Although changes of single ion channels must be interpreted in context of the complex atrial electrophysiology as a whole, our results provide a possible explanation of the in vivo observation that angiotensin-converting enzyme inhibition is mainly beneficial on the early electrical remodelling due to the atrial fibrillation-equivalent RAP. SN - 1752-8976 UR - https://www.unboundmedicine.com/medline/citation/18957382/Inhibition_of_the_renin_angiotensin_system:_effects_on_tachycardia_induced_early_electrical_remodelling_in_rabbit_atrium_ L2 - https://journals.sagepub.com/doi/10.1177/1470320308095262?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -