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.
In conclusion: (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.