Permissive and obligatory roles of NO in cerebrovascular responses to hypercapnia and acetylcholine
Permissive and obligatory roles of NO in cerebrovascular responses to hypercapnia and acetylcholine
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DOI：
10.1152/ajpregu.1996.271.4.r990
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发表时间：
1996-10-01
影响因子：
2.8
通讯作者：
Zhang, FY
中科院分区：
文献类型：
--
作者：
Iadecola, C;Zhang, FY
一氧化氮 (NO) 合成的抑制可减弱乙酰胆碱 (ACh) 产生的高碳酸血症脑血管舒张或脑血流量 (CBF) 的增加，乙酰胆碱 (ACh) 可以局部应用，也可以通过刺激基底前脑胆碱能系统在新皮质中内源性释放。我们研究了使用 NO 供体外源给予 NO 是否可以逆转 NO 合酶 (NOS) 抑制剂对这些反应的减弱作用。在氟烷麻醉、通气的大鼠中，暴露额顶皮质并用林格液灌注。通过激光多普勒血流计监测灌注部位的 CBF。用立体定向植入的微电极刺激基底前脑（100μA；50Hz）。灌输 NOS 抑制剂 NG-硝基-L-精氨酸（L-NNA；1 mM）可减少静息 CBF（-38 +/- 2%；平均值 +/- SE），并减弱高碳酸血症（PCO2，50-60 mmHg；-79 +/- 3%）、ACh（10 mu M；-83 +/- 7%）或基础前脑刺激引起的血管舒张(-44 +/- 2%)（P < 0.05，方差分析和 Tukey 检验）。 L-NNA 后，局部应用 3-吗啉代亚胺 (SIN-1) (n = 7)、S-亚硝基-N-乙酰青霉胺 (SNAP) (n = 6) 或 8-溴鸟苷 3',5'-单磷酸 (8-BrcGMP，n = 4) 重建静息 CBF（P > 0.05，林格氏分析）并逆转对 L-NNA 的反应衰减。高碳酸血症（Ringer P > 0.05）。然而，SIN-1 或 SNAP 未能逆转对基础前脑刺激或局部 ACh 的反应衰减（与 L-NNA 相比，P > 0.05）。 L-NNA 后，NO 依赖性血管扩张剂罂粟碱 (= 4) 重建了静息 CBF（P > 0.05，根据林格法），但未能恢复高碳酸血症血管舒张（P > 0.05，根据 L-NNA）。神经元 NOS 抑制剂 7-硝基吲唑对高碳酸血症反应的减弱仅被 SIN-1 (n = 4) 或 8-BrcGMP (n = 4) 部分抵消。数据支持这样的假设：高碳酸血症引起的血管舒张需要静息水平的 NO 才能表达，而对内源性或外源性 ACh 的反应取决于激动剂诱导的 NOS 激活。在高碳酸血症中，NO 可能通过促进其他血管扩张剂的作用而充当允许因子，而在由 ACh 引发的血管反应中，NO 可能是平滑肌松弛的主要介质。
Inhibition of nitric oxide (NO) synthesis attenuates the hypercapnic cerebrovasodilation or the increases in cerebral blood flow (CBF) produced by acetylcholine (ACh), either topically applied or endogenously released in neocortex by stimulation of the basal forebrain cholinergic system. We investigated whether exogenous administration of NO, using NO donors, can reverse the attenuation of these responses by NO synthase (NOS) inhibitors. In halothane-anesthetized, ventilated rats the frontoparietal cortex was exposed and superfused with Ringer. CBF was monitored at the superfusion site by laser-Doppler flowmetry. The basal forebrain was stimulated (100 mu A; 50 Hz) with microelectrodes stereotaxically implanted. Superfusion with the NOS inhibitor NG-nitro-L-arginine (L-NNA; 1 mM) reduced resting CBF (-38 +/- 2%; mean +/- SE) and attenuated the vasodilation elicited by hypercapnia (PCO2, 50-60 mmHg; -79 +/- 3%), ACh (10 mu M; -83 +/- 7%), or basal forebrain stimulation (-44 +/- 2%) (P < 0.05, analysis of variance and Tukey's test). After L-NNA, topical application of 3-morpholinosydnonimine (SIN-1) (n = 7), S-nitroso-N-acetylpenicillamine (SNAP) (n = 6), or 8-bromoguanosine 3',5'-monophosphate (8-BrcGMP, n = 4) reestablished resting CBF (P > 0.05 from Ringer) and reversed the attenuation of the response to hypercapnia (P > 0.05 from Ringer). However SIN-1 or SNAP failed to reverse the attenuation of the response to basal forebrain stimulation or topical ACh (P > 0.05 from L-NNA). After L-NNA, the NO-independent vasodilator papaverine in. = 4) reestablished resting CBF (P > 0.05 from Ringer) but failed to restore the hypercapnic vasodilation (P > 0.05 from L-NNA). The attenuation of hypercapnic response by the neuronal NOS inhibitor 7-nitroindazole was counteracted only partially by SIN-1 (n = 4) or 8-BrcGMP (n = 4). The data support the hypothesis that the vasodilation elicited by hypercapnia requires resting levels of NO for its expression, whereas the response to endogenous or exogenous ACh depends on agonist-induced NOS activation. In hypercapnia NO may act as a permissive factor by facilitating the action of other vasodilators, whereas in the vascular response initiated by ACh NO is Likely to be the major mediator of smooth muscle relaxation.