Endogenous heme oxygenase prevents impairment of cerebral vascular functions caused by seizures
Endogenous heme oxygenase prevents impairment of cerebral vascular functions caused by seizures
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DOI：
10.1152/ajpheart.00091.2003
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发表时间：
2003-09-01
影响因子：
4.8
通讯作者：
Parfenova, H
中科院分区：
文献类型：
--
作者：
Carratu, P;Pourcyrous, M;Parfenova, H
在新生猪中，癫痫发作引起的脑充血的机制涉及一氧化碳（CO），一氧化碳是血红素加氧酶（HO）分解代谢的血管舒张产物。我们假设当 HO 活性受到抑制时，癫痫发作会导致脑血管功能障碍。通过使用颅窗技术，我们在盐水对照和用 HO 抑制剂锡原卟啉 (SnPP) 预处理的动物中，检查了荷包牡丹碱诱发的癫痫发作恢复过程中，脑血管对内皮依赖性（高碳酸血症和缓激肽）和内皮非依赖性（异丙肾上腺素和硝普钠）扩张剂的反应。 SnPP（3 mg/kg iv）可阻止血红素扩张，并降低皮质蛛网膜周围脑脊液中的 CO 水平，表明 H2O 抑制大脑微循环。在盐水对照仔猪中，癫痫发作增加了 CO 水平，这与时间依赖性脑血管舒张相关。在恢复期间（癫痫发作诱导后 2 小时），对所有血管扩张剂的反应均得以保留。在接受 SnPP 治疗的动物中，脑血管舒张和 CO 对癫痫发作的反应大大降低，并且在恢复过程中脑血管反应性严重受损。这些发现表明，大脑微循环中的 H2O 在癫痫发作期间迅速激活，并提供内源性保护以防止癫痫引起的血管损伤。
In newborn pigs, the mechanism of seizure-induced cerebral hyperemia involves carbon monoxide ( CO), the vasodilator product of heme catabolism by heme oxygenase (HO). We hypothesized that seizures cause cerebral vascular dysfunction when HO activity is inhibited. With the use of cranial window techniques, we examined cerebral vascular responses to endothelium-dependent ( hypercapnia and bradykinin) and endothelium-independent ( isoproterenol and sodium nitroprusside) dilators during the recovery from bicuculline-induced seizures in saline controls and in animals pretreated with a HO inhibitor, tin protoporphyrin ( SnPP). SnPP ( 3 mg/kg iv) blocked dilation to heme and reduced the CO level in cortical periarachnoid cerebrospinal fluid, indicating HO inhibition in the cerebral microcirculation. In saline control piglets, seizures increased the CO level, which correlated with the time-dependent cerebral vasodilation; during the recovery ( 2 h after seizure induction), responses to all vasodilators were preserved. In SnPP-treated animals, cerebral vasodilation and the CO responses to seizures were greatly reduced, and cerebral vascular reactivity was severely impaired during the recovery. These findings suggest that HO in the cerebral microcirculation is rapidly activated during seizures and provides endogenous protection against seizure-induced vascular injury.