The combination of dantrolene and nimodipine effectively reduces 5-HT-induced vasospasms in diabetic rats

Diabetics have a higher risk of developing cerebral vasospasms (CVSP) after subarachnoid hemorrhagic stroke than non-diabetics. Serotonin (5-HT) is one of the key vasoconstrictors released in the hemorrhagic blood and an important contributor to the etiology of CVSP. The combination of the ryanodine...

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Bibliographic Details
Published in:Scientific reports 2021-05, Vol.11 (1), p.9852-9852, Article 9852
Main Authors: Román, Marie, García, Laura, Morales, Myrna, Crespo, María J.
Format: Article
Language:English
Subjects:
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Aorta
Calcium
Diabetes
Diabetes mellitus
Etiology
Hemorrhage
Humanities and Social Sciences
multidisciplinary
Nimodipine
Phenylephrine
Rodents
Science
Science (multidisciplinary)
Serotonin
Stroke
Synergistic effect
Vasoconstrictors
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Summary:Diabetics have a higher risk of developing cerebral vasospasms (CVSP) after subarachnoid hemorrhagic stroke than non-diabetics. Serotonin (5-HT) is one of the key vasoconstrictors released in the hemorrhagic blood and an important contributor to the etiology of CVSP. The combination of the ryanodine receptor blocker dantrolene and the Ca2+ channel blocker nimodipine significantly reduces phenylephrine (PHE)-induced vascular contraction in both diabetic and nondiabetic rats, but the effectiveness of this drug combination in reducing 5-HT-induced contraction is unknown. Dose–response curves for the 5-HT-induced contraction (from 0.1 nM to 100 µM) were performed on aortic rings from diabetic and non-diabetic rats after a 30-min incubation period with dantrolene, nimodipine, and both drugs in combination. In diabetic rats, 10 μM of dantrolene alone failed to reduce 5-HT-induced maximal contraction (E max ), but 50 μM reduced this parameter by 34% (n = 7, p 
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-89338-6