Chronic Dantrolene Treatment Does Not Affect Hypertension, but Attenuates Sympathetic Stimulation Enhanced Atrial Fibrillation Inducibility in SHR.
Animals
Anti-Arrhythmia Agents
/ pharmacology
Atrial Fibrillation
/ etiology
Blood Pressure
Dantrolene
/ pharmacology
Disease Models, Animal
Heart
/ innervation
Heart Rate
/ drug effects
Hypertension
/ complications
Male
Rats, Inbred SHR
Rats, Inbred WKY
Ryanodine Receptor Calcium Release Channel
/ drug effects
Sympathetic Nervous System
/ drug effects
atrial fibrillation
blood pressure
dantrolene
hypertension
spontaneously hypertensive rats
Journal
American journal of hypertension
ISSN: 1941-7225
Titre abrégé: Am J Hypertens
Pays: United States
ID NLM: 8803676
Informations de publication
Date de publication:
29 04 2020
29 04 2020
Historique:
received:
22
08
2019
revised:
11
11
2019
accepted:
11
02
2020
pubmed:
16
2
2020
medline:
22
12
2020
entrez:
16
2
2020
Statut:
ppublish
Résumé
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). 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). 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 32060500
pii: 5736361
doi: 10.1093/ajh/hpaa021
doi:
Substances chimiques
Anti-Arrhythmia Agents
0
Ryanodine Receptor Calcium Release Channel
0
Dantrolene
F64QU97QCR
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
407-413Informations de copyright
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