Devine J O, Armstead W M
Department of Anesthesia, University of Pennsylvania, Philadelphia 19104, USA.
Brain Res. 1995 Mar 27;675(1-2):257-63. doi: 10.1016/0006-8993(95)00081-z.
The present study was designed to investigate the role of nitric oxide (NO) and the production of cGMP in the vasodilator response to opioid agonists in newborn pigs equipped with a closed cranial window. Methionine-enkephalin (10(-8), 10(-6) M), an endogenous mu opioid agonist, produced pial artery dilation that was attenuated by L-nitroarginine (LNA, 10(-6) M), an NO synthase inhibitor (10 +/- 1 vs. 4 +/- 1 and 16 +/- 1 vs. 7 +/- 1% for 10(-8), 10(-6) M methionine-enkephalin, respectively). Methionine-enkephalin-induced vasodilation was associated with increased cortical periarachnoid CSF cGMP and these changes in CSF cGMP were attenuated by LNA (354 +/- 11 and 596 +/- 32 vs. 278 +/- 13 and 266 +/- 19 fmol/ml for control and methionine-enkephalin 10(-6) M before and after LNA, respectively). Leucine enkephalin, an endogenous delta agonist, elicited similar changes in pial diameter and CSF cGMP while dynorphin, an endogenous k agonist, produced dilation associated with large increases in CSF cGMP (374 +/- 18 vs. 1054 +/- 45 fmol/ml for control and dynorphin 10(-6) M, respectively). Vascular and biochemical changes for these two opioids were similarly attenuated by LNA. The synthetic selective opioid receptor agonists, DAMGO, DPDPE, deltorphin, and U50,488H (10(-8), 10(-6) M) mu, delta 1, delta 2, and kappa agonists, respectively, also elicited increases in pial artery diameter and CSF cGMP that were similarly attenuated by LNA.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究旨在探讨一氧化氮（NO）的作用以及环磷酸鸟苷（cGMP）的产生在配备闭合式颅窗的新生猪对阿片类激动剂血管舒张反应中的作用。内源性μ阿片类激动剂甲硫氨酸脑啡肽（10^(-8)、10^(-6) M）可引起软脑膜动脉扩张，该作用可被一氧化氮合酶抑制剂L - 硝基精氨酸（LNA，10^(-6) M）减弱（对于10^(-8)、10^(-6) M甲硫氨酸脑啡肽，分别为10±1%对4±1%和16±1%对7±1%）。甲硫氨酸脑啡肽诱导的血管舒张与皮质蛛网膜下腔脑脊液cGMP增加有关，且脑脊液cGMP的这些变化可被LNA减弱（LNA处理前和处理后，对照和10^(-6) M甲硫氨酸脑啡肽的脑脊液cGMP分别为354±11和596±32对278±13和266±19 fmol/ml）。内源性δ激动剂亮氨酸脑啡肽引起软脑膜直径和脑脊液cGMP的类似变化，而内源性κ激动剂强啡肽产生的扩张与脑脊液cGMP大幅增加有关（对照和10^(-6) M强啡肽的脑脊液cGMP分别为374±18对1054±45 fmol/ml）。LNA同样减弱了这两种阿片类药物的血管和生化变化。合成的选择性阿片受体激动剂，DAMGO、DPDPE、Deltorphin和U50,488H（分别为10^(-8)、10^(-6) M的μ、δ1、δ2和κ激动剂）也引起软脑膜动脉直径和脑脊液cGMP增加，且这些变化同样被LNA减弱。（摘要截断于250字）
