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Center for Perinatal Biology, Departments of Physiology/Pharmacology and Obstetrics and Gynecology, School of Medicine, Loma Linda University, Loma Linda, California 92350
Recently, we reported that,
whereas in cerebral arteries of the adult a majority of norepinephrine
(NE)-induced increase in intracellular Ca2+ concentration
([Ca2+]i) comes from release of the
sarcoplasmic reticulum (SR) Ca2+ stores, in the fetus the
SR Ca2+ stores are relatively small, and NE-induced
increase in [Ca2+]i results mainly from
activation of plasma membrane L-type Ca2+ channels
(20). In an effort to establish further the role of L-type
Ca2+ channels in the developing cerebral arteries, we
tested the hypothesis that, in the fetus, increased reliance on
plasmalemmal L-type Ca2+ channels is mediated, in part, by
increased L-type Ca2+ channel density. We used
3H-labeled
(+)isopropyl-4-(2,1,3-benzoxadiazol-4-y1)-1,4-dihydro-(2,6-dimethyl-5-methoxycarbonyl)pyridine-3-carboxylate (PN200-110, isradipine) to measure L-type Ca2+ channel
density (Bmax) in the cerebral arteries, common carotid artery (CCA), and descending aortae of fetal (~140 gestation
days), newborn (7-10 days), and adult sheep. In the cerebral and
common carotid arteries, Bmax values (fmol/mg protein) of
fetuses and newborns were significantly greater than those of adults.
Western immunoblotting assay also revealed that the density of L-type Ca2+ channel protein in the cerebral arteries and CCA was
about twofold greater in the fetus than the adult. Finally, compared
with the adult, fetal cerebral arteries demonstrated a significantly
greater maximum tension and [Ca2+]i in
response to stimulation with the L-type Ca2+ channel
agonist Bay K 8644. In addition, Bay K 8644-stimulated fetal vessels
demonstrated a maximal tension and [Ca2+]i
similar to that observed in response to stimulation with
10
4 NE. These results support the idea that fetal
cerebrovascular smooth muscle relies more on extracellular
Ca2+ and L-type Ca2+ channels for contraction
than does the adult and that this increased reliance is mediated, in
part, by greater L-type Ca2+ channel density. This may have
important implications in the regulation of cerebral blood flow in the
developing organism.
cerebral circulation; norepinephrine; vascular smooth muscle; intracellular calcium; PN200-110; Bay K 8644; fetus; newborn
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