Peroxynitrite but not nitric oxide donors destroys epinephrine: HPLC measurement and rat aorta contractility.
Nitric oxide (NO) and peroxynitrite (ONOO) have been reported to destroy catecholamines. We compared the ability of NO donors and peroxynitrite to decompose epinephrine in both chemical and pharmacological experiments. Epinephrine (1 microM) was incubated with NO donors (SNAP and MAHMA NONOate) and ONOO at a concentration of 0.1 mM in phosphate buffer (pH 7.4; 0.1 M) or Krebs solution for 10 minutes at 37 degrees C. HPLC revealed that the concentration of epinephrine in the presence of NO donors was unaltered. In contrast, peroxynitrite decreased epinephrine concentration more than 20 fold. Similar relationships were obtained in the study of rat thoracic aorta ring contraction. The contractile activity (EC50) of epinephrine in control solutions and after incubation of NE with NO donors did not change. EC50 was measured at 8-10 nM in control solutions and after preincubation with NO donors. However when epinephrine was preincubated with peroxynitrite, no contractile effect was evoked. Therefore, under these experimental conditions peroxynitrite, but not NO donors, was capable of destroying epinephrine.
Shelkovnikov
Stanislav
S
Nephrology Section, Medical and Research Services, Veteran Affairs Greater, Los Angeles Healthcare System at West Los Angeles, Los Angeles, CA 90073, USA. shelkovnikov@pcmagic.net
Gonick
Harvey C
HC
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D020030:Nitric Oxide Donors; D030421:Peroxynitrous Acid; D004837:Epinephrine