title: The Effect Of NO Donor on Calcium Uptake and Reactive Nitrogen Species Production in Mitochondria.
abstract: OBJECTIVE
  NO and reactive nitrogen species (RNS) are thought to be physiologically important effectors of mitochondrial calcium transport, but this issue was not studied in a living organism. According to literature, the modulation of Ca2+ uptake could influence RNS production via the action on mitochondrial NO synthase (mtNOS). The aim of this work was to study the effect of in vivo administration of NO donor nitroglycerine (NG) on matrix Ca2+ accumulation, RNS production and mtNOS activity.
  
  
  METHODS
  Ca2+ uptake was studied spectrophotometrically with arsenazo-III. The amounts of stable RNS (nitrite, nitrate and nitrosothiols) and L-citrulline, the product of enzymatic NOS activity, were determined analytically.
  
  
  RESULTS
  NG administration resulted in dose-dependent short-term increase in Ca2+-uptake accompanied by essential rise in L-citrulline and RNS content in mitochondria. In parallel, dose-dependent elevation of hydroperoxide production was detected. Ca2+-uniporter activity was not affected, but mitochondrial permeability transition pore (MPTP) was effectively blocked by NO.
  
  
  CONCLUSIONS
  Our results indicate that MPTP blockage by NO was the primary cause for the increase in calcium uptake which eventually resulted in the activation of mtNOS and RNS production. Improved Ca2+ accumulation in mitochondria, together with MPTP blockage, may contribute to well-known cardioprotective effects of pharmacological donors of nitric oxide.
authors.affiliation: Circulation department, Bogomoletz Institute of Physiology, NAS of Ukraine, Kiev, Ukraine.
authors.forename: Olga
authors.initials: O
authors.lastname: Akopova
authors.forename: Anatoly
authors.initials: A
authors.lastname: Kotsiuruba
authors.forename: Yulia
authors.initials: Y
authors.lastname: Korkach
authors.forename: Liudmila
authors.initials: L
authors.lastname: Kolchinskaya
authors.forename: Valentina
authors.initials: V
authors.lastname: Nosar
authors.forename: Bronislav
authors.initials: B
authors.lastname: Gavenauskas
authors.forename: Zoya
authors.initials: Z
authors.lastname: Serebrovska
authors.forename: Iryna
authors.initials: I
authors.lastname: Mankovska
authors.forename: Vadim
authors.initials: V
authors.lastname: Sagach
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D002956:Citrulline / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009566:Nitrates / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology*; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000096:biosynthesis*; D026403:S-Nitrosothiols / Q000378:metabolism
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D026361:Reactive Nitrogen Species; D026403:S-Nitrosothiols; D002956:Citrulline; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; D002118:Calcium