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1 Center for Perinatal Biology,
The present
studies examine the hypothesis that multiple adrenergic neuroeffector
mechanisms are not fully developed in fetal, compared with adult, ovine
middle cerebral arteries. In arteries denuded of endothelium and
pretreated with 1 µM atropine to block involvement of muscarinic
receptors, 10 µM capsaicin to deplete sensory peptidergic neurons,
and 10 µM nitro-L-arginine methyl ester
(L-NAME) to block possible
influences from nitric oxidergic innervation, transmural stimulation at
16 Hz increased contractile tensions to 9.5 ± 3.7%
(n = 6) of the potassium maximum in
adult arteries. Corresponding values in fetal arteries, however, were significantly less and averaged only 1.1 ± 0.6%
(n =10). However, postsynaptic
sensitivity to norepinephrine (NE) was similar in the two age groups;
NE pD2 values (
log
EC50) averaged 6.11 ± 0.12 (n = 6) and 6.33 ± 0.09 M
(n = 9) in fetal and adult arteries, respectively. Similarly, NE content measured via HPLC was
also similar in the two age groups and averaged 32.4 ± 5.0 (n = 17) and 32.5 ± 3.9 ng/ng wet
wt (n = 13) in fetal and adult middle cerebral arteries, respectively. In contrast, stimulation-induced NE
release was greater in fetal than in adult arteries, whether calculated
as total mass released [883 ± 184 (n = 17) vs. 416 ± 106 pg NE/mg
wet wt (n = 13)] or as
fractional release [51.1 ± 5.3 (n = 17) vs. 22.8 ± 3.8 pg/pg NE content per pulse × 10
6]. Measured as an
index of synaptic density, neuronal cocaine-sensitive NE uptake was
similar in fetal and adult arteries [1.55 ± 0.40 (n = 10) and 1.84 ± 0.51 pmol/mg wet wt (n = 7),
respectively]. Overall, age-related differences in postsynaptic
sensitivity to NE, NE release, and NE uptake capacity cannot explain
the corresponding age-related differences in response to stimulation.
The data thus suggest that total synaptic volume and cleft width, in
particular, are probably greater and/or that adrenergic corelease of
vasoactive substances other than NE is altered in fetal compared with
adult middle cerebral arteries.
adrenergic innervation; cerebrovascular circulation; norepinephrine; ontogeny; sheep
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