title: Renin-angiotensin system component expression in the HL-1 atrial cell line and in a pig model of atrial fibrillation.
abstract: OBJECTIVE
  Local atrial tissue angiotensin II (AngII) level is elevated in atrial fibrillation (AF), but the mechanism is unknown. We hypothesized that atrial myocytes express all components of the renin-angiotensin system (RAS) and investigated whether rapid depolarization alone is sufficient to increase paracrine AngII production by up-regulating RAS component expression.
  
  
  METHODS
  In the HL-1 atrial cell line, rapid depolarization was induced by rapid field electrical stimulation (RES) at 1.0 V/cm and 600/min (10 Hz) in atrial HL-1 cells. In a pig model of AF, AF was induced by atrial pacing at 600/min in 10 adult pigs and 10 sham-operated pigs for comparison.
  
  
  RESULTS
  In atrial myocytes, RES induced a sustained elevation of intracellular calcium, and up-regulation of angiotensin-converting enzyme (ACE), chymase and angiotensinogen, resulting in increased AngII production. RES-induced AngII production was attenuated by enalapril [ACE inhibitor (ACEI)] and chymostatin (chymase inhibitor). Conditioned medium from RES-stimulated atrial myocytes increased [3H]leucine uptake and atrial natriuretic peptide expression in atrial myocytes, and [3H]proline uptake and collagen type 1 alpha 1 expression in atrial fibroblasts. Both were attenuated by co-incubation with the AngII type 1 receptor blocker (ARB) losartan. In the porcine model, significant structural changes and a similar pattern of changes of RAS components were noted in AF pigs.
  
  
  CONCLUSIONS
  Atrial cells expressed all components of RAS and rapid depolarization alone was sufficient to up-regulate RAS components, increase paracrine AngII production and induce atrial structural changes, which are attenuated by ACEI, ARB and chymase inhibitor.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chia-Ti
authors.initials: CT
authors.lastname: Tsai
authors.forename: Ling-Ping
authors.initials: LP
authors.lastname: Lai
authors.forename: Juey-Jen
authors.initials: JJ
authors.lastname: Hwang
authors.forename: Wen-Pin
authors.initials: WP
authors.lastname: Chen
authors.forename: Fu-Tien
authors.initials: FT
authors.lastname: Chiang
authors.forename: Kuan-Lih
authors.initials: KL
authors.lastname: Hsu
authors.forename: Chuen-Den
authors.initials: CD
authors.lastname: Tseng
authors.forename: Yung-Zu
authors.initials: YZ
authors.lastname: Tseng
authors.forename: Jiunn-Lee
authors.initials: JL
authors.lastname: Lin
mesh_terms: D000804:Angiotensin II / Q000096:biosynthesis*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism / Q000503:physiopathology*; D002460:Cell Line; D004195:Disease Models, Animal; D004558:Electric Stimulation; D015870:Gene Expression; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000235:genetics*; D013552:Swine; D015854:Up-Regulation
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II