PACAP and VIP differentially preserve neurovascular reactivity after global cerebral ischemia in newborn pigs.
PACAP and VIP differentially preserve neurovascular reactivity after global cerebral ischemia in newborn pigs.
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DOI：
10.1016/j.brainres.2009.06.021
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发表时间：
2009-08-04
期刊：
影响因子：
2.9
通讯作者：
Domoki F
中科院分区：
文献类型：
--
作者：
Lenti L;Zimmermann A;Kis D;Oláh O;Tóth GK;Hegyi O;Busija DW;Bari F;Domoki F
腺苷酸环化酶激活多肽（PACAP）和血管活性肠肽（VIP）在许多模型中具有神经保护作用。脑血管反应性（CR）的损害有助于缺血/再灌注（I/R）诱导的神经元损伤。我们测试了PACAP和/或VIP是否保留依赖于内皮和/或神经元功能的I/R敏感性扩张反应的CR。因此，在麻醉/通气仔猪中，通过活体显微镜检查确定I/R前后软膜小动脉直径对高碳酸血症（5- 10%CO2通气）或局部N-甲基-d-天冬氨酸（NMDA，10-4 M）的反应变化。用非血管活性剂量的PACAP（10-8 M）和VIP（10-9 M）局部预处理可防止缺血后CR衰减为高碳酸血症;对于10% CO2，CR值为27±8% vs 92±5%* vs 8 - 8 ±13%*（溶剂vs PACAP 38 vs VIP，CR表示为I/R前反应的百分比，平均值±SEM，n=8-8，*p<0.05）。I/R后，PACAP而非VIP保留了对NMDA的CR，CR值为31±10% vs 87±8%* vs 35±12%（载体vs PACAP 38 vs VIP，n=6-6）。与PACAP不同，VIP诱导的血管舒张尚未在仔猪中进行研究。我们测试VIP诱导的小动脉扩张是否对环氧合酶（考克斯）-1（SC-560，1 mg/kg）、考克斯-2（NS-398，1 mg/kg）、吲哚美辛（5 mg/kg）和一氧化氮合酶（L-NAME，15 mg/kg）的抑制剂敏感。VIP（10-8-10-7-10-6 M，n=8）可诱导16± 3%、33±6%* 和70±8%* 的可重现剂量依赖性血管舒张。除了SC-560和吲哚美辛消除对10-8 M VIP的血管舒张作用外，所有药物均不影响该反应。总之，PACAP和VIP差异保护缺血后CR;独立于其血管舒张作用。
Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are neuroprotective in numerous models. Impairment of cerebrovascular reactivity (CR) contributes to ischemia/reperfusion (I/R)-induced neuronal damage. We tested whether PACAP and/or VIP preserve CR to I/R-sensitive dilator responses dependent on endothelial and/or neuronal function. Accordingly, changes in pial arteriolar diameters in response to hypercapnia (5–10% CO2 ventilation) or topical N-methyl-d-aspartate (NMDA, 10–4 M) were determined before and after I/R via intravital microscopy in anesthetized/ventilated piglets. Local pretreatment with non-vasoactive doses of PACAP (10–8 M) and VIP (10–9 M) prevented the attenuation of postischemic CR to hypercapnia; to 10% CO2, the CR values were 27±8% vs 92±5%* vs 88±13%* (vehicle vs PACAP38 vs VIP, CR expressed as a percentage of the response before I/R, mean±SEM, n=8–8, *p<0.05). PACAP, but not VIP, preserved CR to NMDA after I/R, with CR values of 31±10% vs 87±8%* vs 35±12% (vehicle vs PACAP38 vs VIP, n=6–6). Unlike PACAP, VIP-induced vasodilation has not yet been investigated in the piglet. We tested whether VIP-induced arteriolar dilation was sensitive to inhibitors of cyclooxygenase (COX)-1 (SC-560, 1 mg/kg), COX-2 (NS-398, 1 mg/kg), indomethacin (5 mg/kg), and nitric oxide synthase (L-NAME, 15 mg/kg). VIP (10–8–10–7–10–6 M, n=8) induced reproducible, dose-dependent vasodilation of 16±3%, 33±6%*, and 70±8%*. The response was unaffected by all drugs, except that the vasodilation to 10–8 M VIP was abolished by SC-560 and indomethacin. In conclusion, PACAP and VIP differentially preserve postischemic CR; independent of their vasodilatory effect.
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影响因子：
25
作者：
Choi, YB;Tenneti, L;Lipton, SA
通讯作者：
Lipton, SA
影响因子：
3.6
作者：
LEFFLER, CW;MIRRO, R;ZUCKERMAN, S
通讯作者：
ZUCKERMAN, S
影响因子：
6.3
作者：
Grant, S;Lutz, EM;Wadsworth, RM
通讯作者：
Wadsworth, RM
影响因子：
8.3
作者：
Bari, F;Errico, RA;Busija, DW
通讯作者：
Busija, DW
DOI：
10.1152/ajpheart.00523.2001
发表时间：
2002-04-01
影响因子：
4.8
作者：
Domoki, F;Perciaccante, JV;Bari, F
通讯作者：
Bari, F