Journal
BRAIN RESEARCH
Volume 1283, Issue -, Pages 50-57Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2009.06.021
Keywords
Piglet; Pial arteriole; Cranial window; NMDA; Hypercapnia
Categories
Funding
- National Institutes of Health [HL30260, HL65380, HL77731]
- Hungarian Health Science Board [194042006]
- National Scientific Research Fund of Hungary [K68976, K63401, IN69967]
- Hungarian Academy of Sciences
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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% CO(2) ventilation) or topical N-methyl-D-aspartate (NMDA, 10(-4) 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% CO(2), 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. (C) 2009 Elsevier B.V. All rights reserved.
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