title: Nitric oxide delays atrial tachycardia-induced electrical remodelling in a sheep model.
abstract: OBJECTIVE
  Rapid atrial pacing for 1 week leads to decreased expression of endocardial nitric oxide (NO)-synthase and decreased NO concentrations. We hypothesized that increasing NO bioavailability may reduce electrical remodelling induced by atrial tachycardia.
  
  
  RESULTS
  We examined the effect of molsidomine, a NO donor, and N(ω)-nitro-l-arginine methylester (l-NAME), a NO-synthase inhibitor, on electrical remodelling occurring during 4 h of rapid atrial pacing in sheep. Haemodynamic and electrophysiological parameters were measured at baseline, 1 h after the start of the infusion and before the start of pacing, and 2 and 4 h after pacing. We measured the effect of molsidomine on atrial monophasic action potentials (MAPs) in non-instrumented sheep and on l-type Ca(2+) currents and intracellular Ca(2+) concentration ([Ca(2+)](i)) transients in right atrial cells, isolated from control sheep. In control sheep, rapid atrial pacing shortened the atrial effective refractory period (AERP) by 12 ± 0.18% after 4 h, an effect that was unaffected by l-NAME. Infusion of molsidomine increased AERP at baseline (+13.4 ± 1.04%) and transiently attenuated pacing-induced AERP shortening (13.6 ± 0.1% at 2 h). Molsidomine tended to increase MAP duration by 20.7 ± 13.4 ms. Incubation of isolated atrial myocytes with NO donor 3-morpholino-sydnonimine (SIN-1) increased significantly l-type Ca(2+) current and [Ca(2+)](i) transients.
  
  
  CONCLUSIONS
  Infusion of molsidomine, a NO donor, delayed shortening of the action potential during short-term rapid atrial pacing, by increasing [Ca(2+)](i). Whereas the former could be protective against repetitive short episodes of atrial fibrillation, the latter might be detrimental in the long term.
authors.affiliation: Department of Cardiovascular Medicine, University of Leuven, Leuven, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Lenaerts
authors.forename: Patricia
authors.initials: P
authors.lastname: Holemans
authors.forename: Peter
authors.initials: P
authors.lastname: Pokreisz
authors.forename: Karin R
authors.initials: KR
authors.lastname: Sipido
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens
authors.forename: Hein
authors.initials: H
authors.lastname: Heidbüchel
authors.forename: Rik
authors.initials: R
authors.lastname: Willems
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D008981:Molsidomine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects / Q000502:physiology; D012756:Sheep; D013612:Tachycardia, Ectopic Atrial / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
chemical_list: D020746:Calcium Channels, L-Type; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D008981:Molsidomine; D002118:Calcium