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Novel mitochondrial mechanisms mediate enhanced vasodilation of rat middle cerebral arteries to mitochondrial depolarization following ischemia‐reperfusion injury
Author(s) -
Rutkai Ibolya,
Wappler Edina A,
Katakam Prasad V.G.,
Liu Dan,
Busija David W
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1131.10
Subject(s) - depolarization , mitochondrion , mitochondrial fission , medicine , diazoxide , chemistry , ischemia , endocrinology , membrane potential , vasodilation , mitochondrial permeability transition pore , reperfusion injury , microbiology and biotechnology , anesthesia , biology , biochemistry , programmed cell death , apoptosis , insulin
Mitochondrial depolarization leads to vasodilation via activation of SR/ER Ca 2+ release. Our objective was to determine the role of mitochondria in vasodilation of middle cerebral arteries (MCA) following ischemia‐reperfusion injury (I‐RI). Male Sprague Dawley rats were subjected to 90 minutes MCA occlusion followed by 48 hours reperfusion. Vasodilation in response to bradykinin (BK), nitroprusside (NTP) and mitochondrial depolarization by diazoxide (DZ, a mitochondrial K ATP channel activator) was determined in isolated MCAs by videomicroscopy. Mitochondrial membrane potential (Ψm)was determined by fluorescence microscopy with specific fluoroprobe, TMRE. Western blots determined the expression of markers of mitochondrial biogenesis [Fusion: mitofusins 1 & 2 (MFNs) and Fission: dynamin‐related protein 1 (DRP1)], voltage‐dependent anion channels (VDAC), ER stress (phosphorylated eukaryotic initiation factor 2 α subunit (p‐eIF2α) and neuronal nitric oxide synthase (nNOS). DZ induced vasodilation was enhanced on ipsilateral MCA (iMCA) compared to contralateral (cMCA) whereas BK and NTP responses were similar. Mitochondrial in iMCA displayed increased baseline Ψm and enhanced depolarization to DZ compared to cMCA. Expression of MFNs and VDAC were unchanged, DRP1 was decreased and nNOS and p‐eIF2α were increased in iMCA. Thus, MCAs respond to I‐RI by reduced mitochondrial fission and increasing Ψm leading to increased ROS response to depolarization, ER Ca 2+ release and nNOS activation.