Vascular pro-oxidant effects secondary to the autoxidation of gallic acid in rat aorta

摘要

Gallic acid autoxidation was monitored by absorption spectroscopy and HO production; vascular effects related to the autoxidation process were studied on intact and rubbed aortic rings from WKY rats. Gallic acid autoxidation in an oxygenated physiological salt solution (37pC, pH=7.4) mostly occurred in a 2-h time period. Superoxide anions, HO and gallic acid quinones were produced during gallic acid autoxidation. In rings partially precontracted with phenylephrine, 0.1-3 oM gallic acid induced marked and largely endothelium-dependent contractions, 10-30 oM gallic acid induced endothelium-independent contractions and 0.1-0.3 mM gallic acid induced complete, fast-developing, endothelium-independent relaxations. Superoxide dismutase (SOD) shifted the endothelium-dependent gallic acid contractions to the right, and N G-nitro-l-arginine abolished them. Indomethacin suppressed the endothelium-independent gallic acid contractions, and catalase abolished the endothelium-independent contractions and relaxations. Gallic acid (30 oM) inhibited the relaxant effects of acetylcholine and sodium nitroprusside. In rings maximally precontracted with KCl, 0.1-100 oM gallic acid did not modify the tone, whereas 0.3 mM induced complete, slow-developing, endothelium-independent relaxations. Moreover, 0.3 mM gallic acid induced an irreversible impairment of ring reactivity and the release of lactate dehydrogenase. Catalase and N-acetyl cysteine suppressed the deleterious effects induced by gallic acid in the rings. In conclusion: (a) gallic acid is rapidly and nonenzymatically oxidized in physiological solutions, generating superoxide anions, HO and quinones; (b) superoxide anions (by destroying NO) and low HO levels (by activating cyclooxygenase) both increase vascular tone; (c) moderate HO levels decrease vascular tone; (d) high HO and quinone levels cause irreversible relaxations due to cellular damage.