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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
To test the hypothesis
that sarcoplasmic reticulum (SR) Ca2+ stores play a key
role in norepinephrine (NE)-induced contraction of fetal and adult
cerebral arteries and that Ca2+ stores change with
development, we performed the following study. In main branch middle
cerebral arteries (MCA) from near-term fetal (~140 days) and
nonpregnant adult sheep, we measured NE-induced contraction and
intracellular Ca2+ concentration
([Ca2+]i) in the absence and presence of
different blockers. In adult MCA, after thapsigargin (10
6
M), the NE-induced responses of tension and
[Ca2+]i were 37 ± 5 and 47 ± 7%,
respectively, of control values (P < 0.01 for each).
In the fetal artery, in contrast, this treatment resulted in no
significant changes from control. When this was repeated in the absence
of extracellular Ca2+, adult MCA increases in tension and
[Ca2+]i were 32 ± 5 and 13 ± 3%,
respectively, of control. Fetal cerebral arteries, however, showed
essentially no response. Ryanodine (RYN, 3 × 106 to
105 M) resulted in increases in tension and
[Ca2+]i in both fetal and adult MCA similar
to that seen with NE. For both adult and fetal MCA, the increased
tension and [Ca2+]i responses to RYN were
essentially eliminated in the presence of zero extracellular
Ca2+. These findings provide evidence that in fetal MCA, in
contrast to those in the adult, SR Ca2+ stores are of less
importance in NE-induced contraction, with such contraction being
almost wholly dependent on Ca2+ flux via plasma membrane
L-type Ca2+ channels. In addition, they suggest that in
both adult and fetal MCA, the RYN receptor is coupled to the plasma
membrane Ca2+-activated K+ channel and/or
L-type Ca2+ channel.
cerebrovascular circulation; vascular smooth muscle; sympathetic nervous system; norepinephrine; intracellular calcium; thapsigargin; cyclopiazonic acid; ryanodine; L-type calcium channel; fetus; adult
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