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Laboratory for Research in Neonatal Physiology, Departments of Physiology and of Pediatrics, The University of Tennessee Health Science Center, Memphis, Tennessee 38163
Specific cerebrovascular
dilatory responses in newborn piglets are entirely prostanoid
dependent, but require both nitric oxide (NO) and prostanoids in
juveniles. We examined endothelial dependency and mechanisms of NO- and
prostanoid-mediated cerebrovascular responses in anesthetized newborn
and juvenile pigs implanted with closed cranial windows. Light/dye
endothelial injury inhibited newborn and juvenile hypercapnic and
bradykinin (BK) responses and inhibited dilation to acetylcholine in
juveniles. Iloprost and NO act permissively in restoring light/dye
inhibited newborn and juvenile responses, respectively. Differences in
sensitivity to iloprost and sodium nitroprusside were not observed.
Juvenile (not newborn) hypercapnic and BK cerebrovascular responses
were sensitive to soluble guanylyl cyclase inhibition. Pial arteriolar diameter and cortical production of prostacyclin, cAMP, and cGMP in
response to BK were measured under control conditions, after treatment
with indomethacin and/or
N
-nitro-L-arginine methyl ester
(L-NAME). Indomethacin inhibited BK responses in newborns.
Juvenile responses were inhibited by L-NAME, and mildly by
indomethacin. Cortical 6-keto-PGF1
, cAMP, and cGMP
increased in response to BK in both age groups. Newborn cerebrovascular
responses are largely NO independent, but NO becomes more important
with maturation.
cranial window; cerebral circulation; permissive; age; nitric oxide
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