Increased platelet-activating factor-induced periventricular brain microvascular constriction associated with immaturity.
Oxidant stress contributes to the pathogenesis of hypoxic-ischemic encephalopathies. Platelet-activating factor (PAF) is generated during oxidant stress. We studied the vasomotor mode of actions of PAF on periventricular (PV) microvessels of fetal ( approximately 75% of term), newborn (1-3 days), and adult pigs. PAF constricted PV microvessels from fetal (29.27 +/- 2.6%) and newborn (22.14 +/- 3.2%) pigs but was ineffective in adults (<2.5%). Specific [(3)H]PAF binding was greater in fetus and newborn than in adults; a concordant developmental PAF-induced inositol phosphate formation was observed. PAF-induced vasoconstriction was abrogated by thromboxane A(2) (TXA(2)) synthase and receptor inhibitors, calcium channel blockers, and by removal of endothelium; vasoconstriction to TXA(2) mimetic U-46619 did not differ with age. Immunoreactive TXA(2) synthase expression and PAF-evoked TXA(2) formation revealed a fetus> newborn>adult profile. Thus the greater PAF-induced PV microvascular constriction in younger subjects seems attributable to greater PAF receptor density and mostly secondary to TXA(2) formation from endothelium. The resulting decrease in blood flow may contribute to the increased vulnerability of the PV brain regions to oxidant stress-induced injury in immature subjects.
Hou
Xin
X
Centre de Recherche de l'Hôpital Sainte-Justine, Department of Pediatrics and Pharmacology, Université de Montréal, Montréal, H3T 1C5.
Gobeil
Fernand
F
Marrache
Anne Marilise
AM
Quiniou
Christiane
C
Brault
Sonia
S
Checchin
Daniella
D
Bernier
Sylvie G
SG
Sennlaub
Florian
F
Joyal
Jean-Sebastien
JS
Abran
Daniel
D
Peri
Krishna
K
Varma
Daya R
DR
Chemtob
Sylvain
S
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000098:blood supply* / Q000187:drug effects* / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005333:Fetus / Q000187:drug effects / Q000502:physiology; D007295:Inositol Phosphates / Q000378:metabolism; D016015:Logistic Models; D010972:Platelet Activating Factor / Q000494:pharmacology*; D013552:Swine / Q000502:physiology; D013929:Thromboxane B2 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D007295:Inositol Phosphates; D010972:Platelet Activating Factor; D013929:Thromboxane B2; D002118:Calcium