Thompson B G, Pluta R M, Girton M E, Oldfield E H
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
J Neurosurg. 1996 Jan;84(1):71-8. doi: 10.3171/jns.1996.84.1.0071.
The authors sought to develop a model for assessing in vivo regulation of cerebral vasoregulation by nitric oxide (NO), originally described as endothelial-derived relaxing factor, and to use this model to establish the role of NO in the regulation of cerebral blood flow (CBF) in primates. By using regional intraarterial perfusion, the function of NO in cerebral vasoregulation was examined without producing confounding systemic physiological effects. Issues examined were: whether resting vasomotor tone requires NO; whether NO mediates vasodilation during chemoregulation and autoregulation of CBF; and whether there is a relationship between the degree of hypercapnia and hypotension and NO production. Twelve anesthetized (0.5% isoflurane) cynomolgus monkeys were monitored continuously for cortical CBF, PaCO2, and mean arterial pressure (MAP), which were systematically altered to provide control and experimental curves of chemoregulation (CBF vs. PaCO2) and autoregulation (CBF vs. MAP) during continuous intracarotid infusion of 1) saline and 2) an NO synthase inhibitor (NOSI), either L-n-monomethyl arginine or nitro L-arginine. During basal conditions (PaCO2 of 38-42 mm Hg) NOSI infusion of internal carotid artery (ICA) reduced cortical CBF from 62 (saline) to 53 ml/100 g/per minute (p<0.01), although there was no effect on MAP. Increased CBF in response to hypercapnia was completely blocked by ICA NOSI. The difference in regional (r)CBF between ICA saline and NOSI infusion increased linearly with PaCO2 when PaCO2 was greater than 40 mm Hg, indicating a graded relationship of NO production, increasing PaCO2, and increasing CBF. Diminution of CBF with NOSI infusion was reversed by simultaneous ICA infusion of L-arginine, indicating a direct role of NO synthesis in the chemoregulation of CBF. Hypotension and hypertension were induced with trimethaphan camsylate (Arfonad) and phenylephrine at constant PaCO2 (40 +/- 1 mm Hg). Autoregulation in response to changes in MAP from 50 to 140 mm Hg was unaffected by ICA infusion of NOSI. In primates, cerebral vascular tone is modulated in vivo by NO; continuous release of NO is necessary to maintain homeostatic cerebral vasodilation; vasodilation during chemoregulation of CBF is mediated directly by NO production; autoregulatory vasodilation with hypertension is not mediated by NO; and increasing PaCO2 induces increased NO production.
作者试图建立一种模型，用于评估一氧化氮（NO，最初被描述为内皮源性舒张因子）对脑血管调节的体内调控作用，并利用该模型确定NO在灵长类动物脑血流量（CBF）调节中的作用。通过局部动脉内灌注，在不产生混淆性全身生理效应的情况下，研究了NO在脑血管调节中的功能。研究的问题包括：静息血管舒缩张力是否需要NO；在CBF的化学调节和自动调节过程中，NO是否介导血管舒张；以及高碳酸血症和低血压程度与NO生成之间是否存在关系。对12只麻醉（0.5%异氟烷）的食蟹猴持续监测皮质CBF、动脉血二氧化碳分压（PaCO2）和平均动脉压（MAP），在持续颈内动脉输注1）生理盐水和2）一种NO合酶抑制剂（NOSI，L - n - 单甲基精氨酸或硝基L - 精氨酸）期间，系统地改变这些参数，以提供化学调节（CBF与PaCO2）和自动调节（CBF与MAP）的对照和实验曲线。在基础条件下（PaCO2为38 - 42 mmHg），颈内动脉（ICA）输注NOSI使皮质CBF从62（生理盐水）降至53 ml/100 g/分钟（p<0.01），尽管对MAP没有影响。ICA输注NOSI完全阻断了因高碳酸血症引起的CBF增加。当PaCO2大于40 mmHg时，ICA输注生理盐水和NOSI时局部（r）CBF的差异随PaCO2呈线性增加，表明NO生成、PaCO2增加和CBF增加之间存在分级关系。同时ICA输注L - 精氨酸可逆转NOSI输注引起的CBF降低，表明NO合成在CBF的化学调节中起直接作用。在恒定PaCO2（40±1 mmHg）下，用樟磺咪芬（阿方那特）和去氧肾上腺素诱导低血压和高血压。ICA输注NOSI不影响MAP从50至140 mmHg变化时的自动调节。在灵长类动物中，脑血管张力在体内受NO调节；持续释放NO对于维持稳态脑血管舒张是必要的；CBF化学调节期间的血管舒张直接由NO生成介导；高血压时的自动调节血管舒张不由NO介导；并且PaCO2增加诱导NO生成增加。
