Formation of the NO donors glyceryl mononitrate and glyceryl mononitrite from the reaction of peroxynitrite with glycerol.
Peroxynitrite (ONOO-), formed from the rapid reaction of superoxide (O2-.) with NO, is known to generate stable compounds capable of donating NO on reaction with thiols and molecules containing hydroxy groups. Using glycerol as a model compound for the reactions of ONOO- with biomolecules containing hydroxy groups, we separated the products and identified them by HPLC/MS. It was shown that both glyceryl mononitrate and glyceryl mononitrite were formed and released NO on incubation with copper and l-cysteine. The compounds were stable over a period of 4h when shielded from light and kept on ice. Slow spontaneous decomposition occurred in the buffer used for the bioassay, but this was not sufficient to explain the vasorelaxing properties of these NO donors. It is concluded that the stable organic nitrate and nitrite have the capacity to be metabolized by vascular tissues, resulting in vasorelaxation.
White
C R
CR
Department of Medicine, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294-0019, USA.
Moellering
D
D
Patel
R P
RP
Kirk
M
M
Barnes
S
S
Darley-Usmar
V M
VM
D000818:Animals; D001011:Aorta / Q000187:drug effects; D005990:Glycerol / Q000737:chemistry*; D009566:Nitrates / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry*; D009573:Nitrites / Q000737:chemistry* / Q000494:pharmacology; D005996:Nitroglycerin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D016877:Oxidants / Q000737:chemistry; D011817:Rabbits; D014665:Vasodilator Agents / Q000737:chemistry*
D009566:Nitrates; D009573:Nitrites; D016877:Oxidants; D014665:Vasodilator Agents; C039642:peroxynitric acid; C014686:mononitroglycerol; D009569:Nitric Oxide; D005996:Nitroglycerin; D005990:Glycerol