We previously found that endothelin-1(1-31) (ET-1(1-31)) exhibited a pro-arrhythmogenic effect in isolated rat hearts. In this study, we further investigated the effects of ET-1(1-31) on a cell viability and observed [Ca(2+)](i) in cultured cardiomyocytes. Cultured neonatal rat cardiomyocytes were treated with 0.1, 1, and 10 nM ET-1(1-31) for 24h in the presence or absence of ET(A) receptor antagonist (BQ(123)) or phosphoramidon, a NEP/ECE inhibitor. Cell injury was evaluated by supernatant lactate dehydrogenase (LDH) assay, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content. Cell viability was assessed by MTT assay. [Ca(2+)](i) was measured with Fluo-3/AM under a laser confocal microscope. 1) ET-1(1-31) dose-dependently increased LDH release and decreased cell viability. 2) LDH and MDA levels were significantly elevated and SOD activity decreased after administration of 1 nM ET-1(1-31) for 24h, and these changes were markedly attenuated by 1 uM BQ(123). 3) Exposure to 10 nM ET 1(1-31) caused a continuous increase in [Ca(2+)](i) to cultured beating cardiomyocytes and termination of [Ca(2+)](i) transient within 6 min, and this change was reversed by 1 uM BQ(123) and attenuated by 0.5 mM phosphoramidon. These results suggest that ET-1(1-31) could cause cell injury, and that the effect of ET-1(1-31) on [Ca(2+)](i) transients is mainly mediated by ET(A) receptor and partially attributed to the conversion of ET-1(1-31) to ET-1(1-21).

• MeSH
• antagonisté endotelinového receptoru A MeSH
• aspartátové endopeptidasy antagonisté a inhibitory   metabolismus   MeSH
• časové faktory MeSH
• cyklické peptidy farmakologie   MeSH
• endotelin-1 analogy a deriváty   farmakologie   MeSH
• financování organizované MeSH
• glykopeptidy farmakologie   MeSH
• inhibitory proteas farmakologie   MeSH
• kardiomyocyty enzymologie   metabolismus   účinky léků   MeSH
• konfokální mikroskopie MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• L-laktátdehydrogenasa metabolismus   MeSH
• malondialdehyd metabolismus   MeSH
• metaloendopeptidasy antagonisté a inhibitory   metabolismus   MeSH
• novorozená zvířata MeSH
• peptidové fragmenty farmakologie   MeSH
• potkani Sprague-Dawley MeSH
• receptor endotelinu A metabolismus   MeSH
• superoxiddismutasa metabolismus   MeSH
• vápníková signalizace účinky léků   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH