Abstract
In the present study, we tested the hypothesis that norepinephrine by modulating myocardial voltage‐dependent anion channel (VDAC)/mitoKATP channels can affect the release of cytochrome C and regulate intrinsic apoptotic cascade. Male Sprague‐Dawley rats (350‐400g) were made septic using 200mg/kg cecal inoculum, ip. Sham animals received 5% dextrose water, ip. VDAC mRNA and protein expression was determined in the myocardium and isolated single adult rat ventricular myocytes (ARVMs) obtained from sham and septic rats. In addition, mitochondria and cytosolic fractions were isolated from ARVM treated with norepinephrine (NE, 10ìmoles) in the presence and absence of 5‐Hydroxydecanoic acid (5HD; 100ìmoles), a selective mitoKATP channel blocker. Sepsis produced a significant down‐regulation of VDAC mRNA and protein along with upregulation of Bax in both myocardium and ARVMs. Pretreatment of septic ARVMs with 5HD blocked NE‐induced decrease in VDAC expression and the release of cytochrome C. These results suggest that sepsis downregulates myocardial VDAC expression. It appears that NE modulates mitoKATP channels and increases the release of cytochrome C, which may play a crucial role in sepsis‐induced cardiomyocyte dysfunction.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
