Vascular pro-oxidant effects related to the autoxidation of dopamine.
Dopamine autoxidation in an oxygenated physiological salt solution (37 degrees C, pH=7.4) mostly occurred in a 2.5 h time period. H(2)O(2) and dopamine quinones were produced during dopamine autoxidation. In partially pre-contracted rat aortic rings, 10-100 microm dopamine induced endothelium-independent contractions and 0.3-1 mm dopamine induced complete, slow-developing endothelium-independent relaxations. Indomethacin and catalase suppressed the endothelium-independent dopamine contractions. Catalase strongly reduced the endothelium-independent dopamine relaxations. Furthermore, 1 mm dopamine for 60 min followed by a 90 min washout period induced the release of lactate dehydrogenase and the complete impairment of ring reactivity to phenylephrine and KCl. Pre-treatment with catalase or glutathione prevented dopamine-induced deleterious effects so that further concentration-response curves to phenylephrine and KCl could be obtained. The phenylephrine potency was maintained in rings pre-treated with glutathione but not in rings pre-treated with catalase.


CONCLUSIONS
(1) dopamine is rapidly and non-enzymatically oxidized in physiological solutions, generating H(2)O(2) and quinones; (2) low H(2)O(2) levels increase vascular tone by activating cyclooxygenase; (3) high H(2)O(2) levels cause irreversible relaxations due to unspecific cellular damage; and (4) dopamine quinones cause a specific alteration in the phenylephrine response.
Fernández-Ferreiro
Alvaro
A
Department of Pharmacology, Universidade de Santiago de Compostela, Spain.
Gil-Longo
José
J
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002374:Catalase / Q000494:pharmacology; D004298:Dopamine / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D016877:Oxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D013056:Spectrophotometry, Ultraviolet
D016877:Oxidants; D011189:Potassium Chloride; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D004298:Dopamine; D007213:Indomethacin