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

被引:43
作者
Tsai, Chia-Ti [2 ]
Lai, Ling-Ping [1 ,3 ]
Hwang, Juey-Jen [3 ]
Chen, Wen-Pin [1 ]
Chiang, Fu-Tien [2 ,4 ]
Hsu, Kuan-Lih [2 ]
Tseng, Chuen-Den [2 ]
Tseng, Yung-Zu [2 ]
Lin, Jiunn-Lee [2 ]
机构
[1] Natl Taiwan Univ, Inst Pharmacol, Taipei 100, Taiwan
[2] Natl Taiwan Univ Hosp, Dept Internal Med, Div Cardiol, Taipei 100, Taiwan
[3] Natl Taiwan Univ Hosp, Dept Internal Med, Yun Lin Branch, Taipei 100, Taiwan
[4] Natl Taiwan Univ Hosp, Dept Lab Med, Taipei, Taiwan
关键词
angiotensin II; atrial fibrillation; atrial fibroblast; atrial myocyte; rapid depolarization; rapid pacing; renin-angiotensin system;
D O I
10.1097/HJH.0b013e3282f34a4a
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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 (10Hz) 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-3]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.
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收藏
页码:570 / 582
页数:13
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