beta-Adrenoceptor and nNOS-derived NO interactions modulate hypoglycemic pial arteriolar dilation in rats.
beta-Adrenoceptor and nNOS-derived NO interactions modulate hypoglycemic pial arteriolar dilation in rats.
复制标题
β-肾上腺素受体和 nNOS 衍生的 NO 相互作用调节大鼠低血糖软脑膜小动脉扩张。
DOI：
10.1152/ajpheart.2001.280.2.h562
复制
发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Pelligrino,DA
中科院分区：
文献类型：
--
作者：
Santizo,RA;Koenig,HM;Pelligrino,DA
我们研究了一氧化氮（NO）和儿茶酚胺能途径在低血糖（血糖≤ 1.4 mM）时促进脑小动脉扩张的相对贡献。为此，我们监测了β-肾上腺素受体（β-AR）阻滞剂普萘洛尔的作用（Pro，1.5 mg/kg iv），用7-硝基吲唑抑制神经元型一氧化氮合酶（nNOS）（7-NI，40 mg/kg ip）或ARR-17477（300 μM，局部给药），或联合静脉注射Pro + 7-NI或ARR-17477对胰岛素诱导低血糖的麻醉大鼠软脑膜小动脉直径变化的影响。采用局部应用TTX（1 μM）的其他实验探讨了软脑膜小动脉对低血糖的反应需要神经元传递的可能性。分别地，Pro和7-NI引起伴随低血糖的小动脉直径的正常10 - 40%增加的适度但统计学上不显著的10-20%减少。然而，组合的Pro-7-NI伴随着低血糖诱导的扩张减少>80%。另一方面，静脉注射Pro和局部ARR-17477的组合不影响低血糖反应。在TTX的存在下，软脑膜小动脉对低血糖的反应完全丧失。结果提示：1）β-ARs和nNOS源性NO在低血糖诱导的软脑膜小动脉扩张中相互作用;2）这种相互作用不在小动脉附近发生; 3）血管扩张信号通过神经元通路传递。
We examined the relative contributions from nitric oxide (NO) and catecholaminergic pathways in promoting cerebral arteriolar dilation during hypoglycemia (plasma glucose ≅ 1.4 mM). To that end, we monitored the effects of β-adrenoceptor (β-AR) blockade with propranolol (Pro, 1.5 mg/kg iv), neuronal nitric oxide synthase (nNOS) inhibition with 7-nitroindazole (7-NI, 40 mg/kg ip) or ARR-17477 (300 μM, via topical application), or combined intravenous Pro + 7-NI or ARR-17477 on pial arteriolar diameter changes in anesthetized rats subjected to insulin-induced hypoglycemia. Additional experiments, employing topically applied TTX (1 μM), addressed the possibility that the pial arteriolar response to hypoglycemia required neuronal transmission. Separately, Pro and 7-NI elicited modest but statistically insignificant 10–20% reductions in the normal ∼40% increase in arteriolar diameter accompanying hypoglycemia. However, combined Pro-7-NI was accompanied by a >80% reduction in the hypoglycemia-induced dilation. On the other hand, the combination of intravenous Pro and topical ARR-17477 did not affect the hypoglycemia response. In the presence of TTX, the pial arteriolar response to hypoglycemia was lost completely. These results suggest that1) β-ARs and nNOS-derived NO interact in contributing to hypoglycemia-induced pial arteriolar dilation;2) the interaction does not occur in the vicinity of the arteriole; and3) the vasodilating signal is transmitted via a neuronal pathway.