Renin-angiotensin system component expression in the HL-1 atrial cell line and in a pig model of atrial fibrillation

Chia Ti Tsai, Ling Ping Lai, Juey Jen Hwang, Wen Pin Chen, Fu Tien Chiang, Kuan Lih Hsu, Chuen Den Tseng, Yung Zu Tseng, Jiunn Lee Lin

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37 Citations (Scopus)

Abstract

OBJECTIVES: 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 [H]leucine uptake and atrial natriuretic peptide expression in atrial myocytes, and [H]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.

Original languageEnglish
Pages (from-to)570-582
Number of pages13
JournalJournal of Hypertension
Volume26
Issue number3
DOIs
Publication statusPublished - Mar 1 2008
Externally publishedYes

Keywords

  • Angiotensin II
  • Atrial fibrillation
  • Atrial fibroblast
  • Atrial myocyte
  • Rapid depolarization
  • Rapid pacing
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

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  • Cite this

    Tsai, C. T., Lai, L. P., Hwang, J. J., Chen, W. P., Chiang, F. T., Hsu, K. L., Tseng, C. D., Tseng, Y. Z., & Lin, J. L. (2008). Renin-angiotensin system component expression in the HL-1 atrial cell line and in a pig model of atrial fibrillation. Journal of Hypertension, 26(3), 570-582. https://doi.org/10.1097/HJH.0b013e3282f34a4a