Pacap and vip differentially preserve neurovascular reactivity after global cerebral ischemia in newborn pigs.

Lenti, L. and Zimmermann, A. and Kis, Dávid and Oláh, Orsolya and Tóth, Gábor and Hegyi, Orsolya and Bari, Ferenc and Domoki, Ferenc (2009) Pacap and vip differentially preserve neurovascular reactivity after global cerebral ischemia in newborn pigs. BRAIN RESEARCH, 1283. pp. 50-57. ISSN 0006-8993

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Abstract

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. Wetestedwhether 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, dosedependent vasodilation of 16±3%, 33±6%⁎, and 70±8%⁎. The response was unaffected by all drugs, except that the vasodilation to 10−8MVIP 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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