Abstract:
BACKGROUND:Ryanodine receptor (RyR) dysfunction in skeletal muscle (RyR1) leads to malignant hyperthermia, and in cardiac muscle (RyR2) triggers cardiac arrhythmias. We hypothesized that RyR dysfunction in vascular smooth muscle could increase vascular resistance and hypertension, and may contribute to increased atrial fibrillation (AF) in hypertension. Thus, stabilizing RyR function with chronic dantrolene treatment may attenuate hypertension and AF inducibility in spontaneously hypertensive rats (SHR). METHODS:Male SHR (16 weeks old) were randomized into vehicle- (n = 10) and dantrolene-treated (10 mg/kg/day, n = 10) groups for 4 weeks. Wistar Kyoto (WKY, n = 11) rats served as controls. Blood pressures (BP) were monitored before and during the 4-week treatment. After 4-week treatment, direct BP, echocardiography, and hemodynamics were recorded. AF inducibility tests were performed in vivo at baseline and repeated under sympathetic stimulation (SS). RESULTS:Compared with WKY, SHR had significantly higher BP throughout the experimental period. Dantrolene treatment had no effect on BP levels in SHR (final systolic BP 212 ± 9 mm Hg in vehicle group vs. 208 ± 16 mm Hg in dantrolene group, P > 0.05). AF inducibility was very low and not significantly different between 5-month-old WKY and SHR at baseline. However, under SS, AF inducibility and duration were significantly increased in SHR (20% in WKY vs. 60% in SHR-vehicle, P<0.05). Dantrolene treatment significantly attenuated AF inducibility under SS in SHR (60% in vehicle vs. 20% in dantrolene, P < 0.05). CONCLUSIONS:Stabilizing RyR with chronic dantrolene treatment does not affect hypertension development in SHR. SHR has increased vulnerability to AF induction under SS, which can be attenuated with dantrolene treatment.
journal_name
Am J Hypertensjournal_title
American journal of hypertensionauthors
Lee JS,Greco L,Migirov A,Li Y,Gerdes AM,Zhang Ydoi
10.1093/ajh/hpaa021subject
Has Abstractpub_date
2020-04-29 00:00:00pages
407-413issue
5eissn
0895-7061issn
1941-7225pii
5736361journal_volume
33pub_type
杂志文章abstract:BACKGROUND:Components of the renin-angiotensin-aldosterone system (RAAS) and a prothrombotic state are predictors of cardiovascular events in hypertensive patients. A relationship between the RAAS and the coagulation/fibrinolytic systems has been demonstrated, but its clinical relevance in hypertension is unclear. We i...
journal_title:American journal of hypertension
pub_type: 杂志文章
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journal_title:American journal of hypertension
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journal_title:American journal of hypertension
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journal_title:American journal of hypertension
pub_type: 杂志文章,随机对照试验
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更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:Peripheral endothelial dysfunction has been demonstrated in hypertension. However, its relationship to blood pressure (BP) load, vascular structure, and metabolic disturbances in patients with long-standing, previously treated hypertension is unclear. METHODS:A total of 41 patients with stage I to III essen...
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abstract::The "totality" of hypertension clinical trial endpoint data has shown that the absolute benefit of pharmacological blood pressure (BP) lowering is directly related to the BP level and baseline cardiovascular risk, albeit with attenuation of the relative risk reduction per unit of BP lowering in patients with diabetes ...
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journal_title:American journal of hypertension
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journal_title:American journal of hypertension
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journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:
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journal_title:American journal of hypertension
pub_type: 杂志文章
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journal_title:American journal of hypertension
pub_type: 杂志文章,评审
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更新日期:2008-10-01 00:00:00
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doi:10.1016/0895-7061(96)00023-4
更新日期:1996-07-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章,评审
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更新日期:2000-06-01 00:00:00
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pub_type: 杂志文章
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pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:American journal of hypertension
pub_type: 杂志文章,meta分析
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更新日期:1994-08-01 00:00:00
abstract::Hypertension is a common finding among obstructive sleep apnea (OSA) patients, and is thought to be caused by sympathetic hyperactivity. The present study compares the contributions of the respiratory disturbance index (RDI) as a reflection of sleep fragmentation, and the magnitude of oxygen desaturation, to sympathet...
journal_title:American journal of hypertension
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pub_type: 杂志文章,评审
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更新日期:1993-05-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
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更新日期:2002-11-01 00:00:00
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更新日期:2019-11-15 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/0895-7061(95)00219-F
更新日期:1995-09-01 00:00:00
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pub_type: 杂志文章
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