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Pituitary adenylate cyclase activating polypeptide (PACAP) preserves pial arteriolar dilation to hypercapnia and N‐methyl‐D‐aspartate (NMDA) after global cerebral ischemia in piglets
Author(s) -
Lenti Laura,
Domoki Ferenc,
Kis David,
Zimmermann Aliz,
Toth Gabor,
Busija David W,
Bari Ferenc
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1151.15
Subject(s) - hypercapnia , neuroprotection , nmda receptor , ischemia , vasodilation , chemistry , anesthesia , endocrinology , medicine , dilator , pharmacology , receptor , acidosis
Impairment of cerebrovascular reactivity (CR) contributes to ischemia/reperfusion (I/R)‐induced neuronal damage. PACAP is neuroprotective in numerous experimental models, but a possible cerebrovascular component in its mechanism of action has not yet been assessed. We tested if PACAP isoforms (PACAP27 and 38) preserve CR to endothelium‐ or neuronal‐dependent I/R‐sensitive dilator responses in newborns. Pial arteriolar diameters (baseline ∼100 μ m) were determined via closed cranial window/intravital microscopy in anesthetized piglets in response to hypercapnia (5–10% CO2 ventilation) or topical NMDA (10 −4 M) before and after I/R. Prior to I/R, non‐vasoactive doses of PACAP27, 38 (10 −8 M, 30 min), or vehicle were applied onto the cortex. I/R attenuated hypercapnia‐ and NMDA‐induced vasodilation, that was preserved both by PACAP27 and 38. For instance, postischemic CR to NMDA (vehicle vs. PACAP38, CR expressed as % of response before I/R, mean±SEM, n=4–6) was 30±12 vs. 86±6, and CR to 10% CO2 was 45±9 vs. 90±7. In conclusion, PACAP‐induced neuroprotection is likely mediated in part by preservation of I/R‐sensitive cerebrovascular mechanisms. Supported by the OTKA (K68976 and K63401) and by the NIH (HL30260, HL65380, HL77731).