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Substance P Receptor Antagonism: A Potential Novel Treatment Option for Viral-Myocarditis
Joint Authors
Firozgary, Bahrom
Bulsara, Tushar
Taffet, George E.
Engineer, Nikita
Khumbatta, Mitra
Reynolds, Corey
Pham, Thuy
Robinson, Prema
Firozgary, Gohar
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-03-02
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Viral-myocarditis is an important cause of heart failure for which no specific treatment is available.
We previously showed the neuropeptide substance P (SP) is associated with the pathogenesis of murine myocarditis caused by encephalomyocarditis virus (EMCV).
The current studies determined if pharmacological inhibition of SP-signaling via its high affinity receptor, NK1R and downstream G-protein, Ras homolog gene family, member-A (RhoA), will be beneficial in viral-myocarditis.
Aprepitant (1.2 mg/kg), a SP-receptor antagonist, or fasudil (10 mg/kg), a RhoA inhibitor, or saline control was administered daily to mice orally for 3 days, prior to, or 5 days following, intraperitoneal infection with and without 50 PFU of EMCV, following which disease assessment studies, including echocardiogram and cardiac Doppler were performed in day 14 after infection.
Pretreatment and posttreatment with aprepitant significantly reduced mortality, heart and cardiomyocyte size, and cardiac viral RNA levels ( P < 0.05 all, ANOVA).
Only aprepitant pretreatment improved heart functions; it significantly decreased end systolic diameter, improved fractional shortening, and increased peak aortic flow velocity ( P < 0.05 all, ANOVA).
Pre- or posttreatment with fasudil did not significantly impact disease manifestations.
These findings indicate that SP contributes to cardiac-remodeling and dysfunction following ECMV infection via its high affinity receptor, but not through the Rho-A pathway.
These studies suggest that SP-receptor antagonism may be a novel therapeutic-option for patients with viral-myocarditis.
American Psychological Association (APA)
Robinson, Prema& Taffet, George E.& Engineer, Nikita& Khumbatta, Mitra& Firozgary, Bahrom& Reynolds, Corey…[et al.]. 2015. Substance P Receptor Antagonism: A Potential Novel Treatment Option for Viral-Myocarditis. BioMed Research International،Vol. 2015, no. 2015, pp.1-12.
https://search.emarefa.net/detail/BIM-1056262
Modern Language Association (MLA)
Robinson, Prema…[et al.]. Substance P Receptor Antagonism: A Potential Novel Treatment Option for Viral-Myocarditis. BioMed Research International No. 2015 (2015), pp.1-12.
https://search.emarefa.net/detail/BIM-1056262
American Medical Association (AMA)
Robinson, Prema& Taffet, George E.& Engineer, Nikita& Khumbatta, Mitra& Firozgary, Bahrom& Reynolds, Corey…[et al.]. Substance P Receptor Antagonism: A Potential Novel Treatment Option for Viral-Myocarditis. BioMed Research International. 2015. Vol. 2015, no. 2015, pp.1-12.
https://search.emarefa.net/detail/BIM-1056262
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1056262