Meng W, Colonna D M, Tobin J R, Busija D W
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1083, USA.
Am J Physiol. 1995 Jul;269(1 Pt 2):H176-81. doi: 10.1152/ajpheart.1995.269.1.H176.
We examined whether blockade of prostaglandin synthesis by indomethacin could attenuate the effect of nitric oxide synthase (NOS) inhibition on cerebral arteriolar dilation during cortical spreading depression (CSD). CSD was induced by microinjection of 5% (670 mM) KCl onto the cerebral cortex of anesthetized adult rabbits. A closed cranial window and intravital microscopy were used to measure pial arteriolar diameter, and NOS activity was determined by the conversion assay of [14C]arginine to [14C]citrulline. CSD dilated pial arterioles by 47 +/- 3% (baseline = 80-88 microns) (n = 21, P < 0.05), and inhibition of NOS by NG-nitro-L-arginine (L-NNA) (15 mg/kg iv) reduced dilation during CSD by over one-half (n = 8, P < 0.05) without altering the onset latency to CSD. After indomethacin administration (15 mg/kg iv), CSD dilated arterioles from 73 +/- 2 to 152 +/- 6 microns (n = 4, P < 0.05). However, after administration of both indomethacin and L-NNA (n = 5), CSD-induced arteriolar dilation was not different from the situation where indomethacin alone was given. Thus indomethacin completely abolished the inhibitory effect of L-NNA on CSD-induced dilation. Administration of L-NNA inhibited NOS activity in brain cortex almost completely (n = 8, P < 0.05), whereas indomethacin itself had no effect (n = 8). In addition, L-NNA inhibited topical acetylcholine (10(-5) M)-induced arteriolar dilation (n = 3, P < 0.05), and this effect was not altered by indomethacin (n = 4). In summary, L-NNA reduced arteriolar dilation during CSD. However, after administration of indomethacin, L-NNA does not reduce CSD-induced arteriolar dilation.
我们研究了吲哚美辛对前列腺素合成的阻断是否能减弱一氧化氮合酶（NOS）抑制对皮质扩散性抑制（CSD）期间脑小动脉扩张的影响。通过向麻醉的成年兔大脑皮层微量注射5%（670 mM）氯化钾诱导CSD。使用封闭的颅骨视窗和活体显微镜测量软脑膜小动脉直径，通过[14C]精氨酸向[14C]瓜氨酸的转化测定来确定NOS活性。CSD使软脑膜小动脉扩张47±3%（基线=80 - 88微米）（n = 21，P < 0.05），NG - 硝基 - L - 精氨酸（L - NNA）（15 mg/kg静脉注射）抑制NOS可使CSD期间的扩张减少一半以上（n = 8，P < 0.05），且不改变CSD的起始潜伏期。给予吲哚美辛（15 mg/kg静脉注射）后，CSD使小动脉从73±2微米扩张至152±6微米（n = 4，P < 0.05）。然而，给予吲哚美辛和L - NNA后（n = 5），CSD诱导的小动脉扩张与仅给予吲哚美辛的情况无差异。因此，吲哚美辛完全消除了L - NNA对CSD诱导扩张的抑制作用。给予L - NNA几乎完全抑制了大脑皮层中的NOS活性（n = 8，P < 0.05），而吲哚美辛本身无作用（n = 8）。此外，L - NNA抑制局部乙酰胆碱（10^(-5) M）诱导的小动脉扩张（n = 3，P < 0.05），且吲哚美辛未改变这种作用（n = 4）。总之，L - NNA减少了CSD期间的小动脉扩张。然而，给予吲哚美辛后，L - NNA不会减少CSD诱导的小动脉扩张。
