The inhibitory effect of trimetazidine on detrusor contractility - a potential repositioning of trimetazidine for the treatment of overactive bladder
Küçük Resim Yok
Tarih
2022
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Oxford Univ Press
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Objectives This study aimed to identify the effect of trimetazidine (TMZ), an antianginal drug, on detrusor smooth muscle (DSM) contractility and its possible mechanisms of action. Methods We performed in-vitro contractility studies on isolated mouse DSM strips and investigated the effect of TMZ on Ca2+ levels in fura-2-loaded A7r5 cells. Key findings TMZ (300 or 1000 mu M) inhibited carbachol (CCh)- and KCl-induced contractions and produced a concentration-dependent (10-1000 mu M) relaxation in KCl-precontracted DSM strips. TMZ-induced relaxation was markedly decreased by BaCl2, an inward-rectifying K+ channel blocker, but was not altered by preincubation with tetraethylammonium, glibenclamide, 4-aminopyridine, propranolol, L-NAME or methylene blue. TMZ (300 or 1000 mu M) reduced both the CaCl2-induced contraction of depolarized DSM strips under Ca2+-free conditions and the CCh-induced contraction of DSM strips preincubated with nifedipine in Ca2+-containing Krebs solution. Furthermore, TMZ (1000 mu M) significantly decreased the Ca2+ levels in fura-2-loaded A7r5 cells. Conclusions TMZ decreased DSM contractility and caused a concentration-dependent relaxation of the tissue possibly through its actions on Ca2+ transients and K+ channels. Our results provide preclinical evidence that TMZ would be a potential candidate to treat disorders related to the overactivity of the bladder.
Açıklama
Anahtar Kelimeler
calcium, detrusor, ion channels, isolated tissue bath, fura-2, trimetazidine, Ion-Channel Gene, Nitric-Oxide, Smooth-Muscle, Ca2+ Influx, Relaxation, Pathophysiology, Physiology, Entry, Pig
Kaynak
Journal of Pharmacy and Pharmacology
WoS Q Değeri
Q2
Scopus Q Değeri
Q1
Cilt
74
Sayı
1
