Peroxynitrite decreases dopamine's vasoconstrictive activity.
Peroxynitrite (ONOO(-1)) reacts with dopamine to form an oxidized derivative. To investigate the vasoconstrictive activity of this derivative, we performed functional examinations with dopamine treated with ONOO(-1) or 3-morpholinosydonimine-N-ethyl-carbamine (SIN-1; an ONOO(-1) producer) on isolated strips of rat thoracic aorta. To exclude the direct effect of ONOO(-1), the strips were pretreated with methylene blue, a guanylyl cyclase inhibitor. Dopamine induced concentration-dependent contraction, but dopamine pretreated with ONOO(-1) decreased the contraction in an ONOO(-1)-concentration-dependent manner. Both maximum contractions and 50% effective concentration values for dopamine-induced vasocontraction were significantly decreased by pretreatment with ONOO(-1). Dopamine incubated with SIN-1 also decreased the contraction, the decrease being dependent on the incubation time. ONOO(-1) formation is a favored reaction and occurs easily when cellular production of both nitric oxide and superoxide increases, as in septic shock. These results may, at least in part, account for dopamine's limitation as a vasoconstrictor in septic shock.


CONCLUSIONS
Peroxynitrite (ONOO(-1)) reacts with dopamine to form an oxidized derivative. We investigated the vasoconstrictive activity of this derivative with functional examinations using rat thoracic aorta and found the activity decreased. As ONOO(-1) formation increases in septic shock, our results may account for dopamine's limitation as a vasoconstrictor in septic shock.
*Department of Anesthesiology, Asahi University, Hozumi, Gifu; and †Department of Anesthesiology and Reanimatology, Fukui Medical University, Matsuoka, Japan.
Ko
K
Takakura
Wen
W
Xiaohong
Kenji
K
Takeuchi
Satoru
S
Fukuda
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects*
D018492:Dopamine Antagonists; D030421:Peroxynitrous Acid; C002385:linsidomine; D008981:Molsidomine; D004298:Dopamine