Hemodynamic effects of metalloporphyrin catalytic antioxidants: structure-activity relationships and species specificity.
Hemodynamic effects of metalloporphyrin catalytic antioxidants: structure-activity relationships and species specificity.
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DOI：
10.1016/s0891-5849(02)01140-1
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发表时间：
2002-12
影响因子：
7.4
通讯作者：
A. D. Ross;H. Sheng;D. Warner;C. Piantadosi;I. Batinic-Haberle;B. Day;J. Crapo
中科院分区：
文献类型：
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作者：
A. D. Ross;H. Sheng;D. Warner;C. Piantadosi;I. Batinic-Haberle;B. Day;J. Crapo
超氧化物在某些血管疾病的血压调节中起作用，然而，其参与调节基础血压是不确定的。血管超氧化物浓度受到细胞外超氧化物歧化酶（EC-SOD）的限制，EC-SOD在大多数动物的血管系统中高度表达。金属卟啉是一种低分子量、合成的、具有氧化还原活性的催化抗氧化剂，可作为SOD模拟物。我们评估了金属卟啉对不同动物血压的影响。金属卟啉AEOL 10113（5-10 μg/kg iv），而不是天然或聚乙二醇-CuZnSOD，引起麻醉大鼠血压的剂量依赖性降低。AEOL 10113对小鼠（野生型或EC-SOD敲除）、豚鼠、狗或狒狒的血压没有影响，剂量高达5 mg/kg iv。结构-活性研究表明，具有高SOD活性的金属卟啉比低活性类似物更有效地降低大鼠血压。AEOL 10113的血压效应不归因于锰的释放，也不受一氧化氮合酶（L-NAME）和鸟苷酸环化酶（ODQ、8-溴-cGMP和亚甲蓝）抑制剂或一氧化氮清除剂（HbAo）的影响。扑尔敏减弱了这种效应，提示大鼠的血压反应与组胺释放有关，而不是一氧化氮的保护作用。
Superoxide plays a role in blood pressure regulation in certain vascular diseases, however, its involvement in regulating basal blood pressure is uncertain. Vascular superoxide concentrations are limited by extracellular superoxide dismutase (EC-SOD), which is highly expressed in the vasculature of most animal species. Metalloporphyrins are low molecular weight, synthetic, redox-active, catalytic antioxidants that act as SOD mimetics. We evaluated the effects of metalloporphyrins on blood pressure in different animal species. The metalloporphyrin AEOL10113 (5–10 μg/kg iv), but not native or polyethylene glycol-CuZnSOD, caused a dose-dependent reduction in blood pressure in anesthetized rats. AEOL10113 had no effect on blood pressure in mice (wild-type or EC-SOD knockouts), guinea pigs, dogs, or baboons at doses up to 5 mg/kg iv Structure-activity studies indicated that metalloporphyrins with high SOD activity were more effective in lowering rat blood pressure than low-activity analogs. The blood pressure effect of AEOL10113 was not attributable to the release of manganese, nor was it affected by inhibitors of nitric oxide synthase (L-NAME) and guanylate cyclase (ODQ, 8-bromo-cGMP, and methylene blue) or nitric oxide scavengers (HbAo). Chlorpheniramine attenuated the effect, suggesting that the blood pressure response in rats is related to histamine release rather than the protection of nitric oxide.