Developmental changes in ne-induced contraction, [alpha]1
-adrenergic receptors, and ins(1,4,5)p3 responses in cerebral
arteries.
Longo, Lawrence D., Nobumi Ueno, Yu Zhao, William J. Pearce, and Lubo
Zhang.
Center for Perinatal Biology, Departments of Physiology,
Pharmacology, and Obstetrics and Gynecology, Loma Linda University
School of Medicine, Loma Linda, CA 92350
APStracts 3:0229H, 1996.
Background. Cerebral arteries show significant developmental and
artery-specific changes in noradrenergic-mediated contraction. To
test the hypothesis that these changes result from differences in the
density of [alpha]1-adrenergic receptors ([alpha]1-AR) and/or
norepinephrine (NE)-induced inositol 1,4,5-trisphosphate
(Ins(1,4,5)P3) synthesis, we quantified these variables and the NE
-induced contraction in common carotid (COM), circle of Willis (WIL),
and anterior, middle, and posterior (AMP) cerebral arteries, from
term fetal (_140 gestational day) and newborn (2-5 day) sheep, and
compared these values to the adult. Results. In fetal and newborn
COM, maximal contractions to NE (% of K+ maximum), were 132+/-14% and
118+/-9%, respectively, as compared to adult of 92+/-7%. For fetal
and newborn MCA, these values were 34+/-10% and 43+/-7%,
respectively, as compared to 24 +/-7% for adult. For each age group
the values of COM were significantly greater than those of AMP.
[alpha]1-AR density values (Bmax, fmol/mg protein) in COM of fetal
and newborn sheep were 113+/-18 and 106+/-4, respectively. These
values contrast with the adult value of 54+/-3. For the AMP cerebral
arteries Bmax values were 47+/-2 and 24+/-3, respectively, and
compare to the adult value of 23+/-3. In WIL vessels of each age
group, [alpha]1AR were not detectable. In term fetal and newborn AMP
cerebral arteries, NE produced dose-dependent increases in
Ins(1,4,5)P3, the maximal increases above basal values being 245+/
-40% and 189+/-16%, respectively. These compare with the adult value
of 254+/-35 above baseline. Neither fetus nor newborn COM or WIL
showed significant Ins(1,4,5) P3 responses to NE. Conclusions. 1) In
fetal and newborn COM and AMP cerebral arteries, [alpha]1-AR density
and NE-induced Ins(1,4,5)P3 response varied as a function of
developmental age and specific vessel. However, these variations did
not correlate with NE-induced maximum contraction. Thus, we reject
the hypothesis that age-dependent and vessel specific differences of
cerebral artery adrenergic-mediated contraction are a function of
[alpha]1-AR density or Ins(1,4,5)P3 response. Rather, the differences
would appear to result from other factors, such as non-Ins(1,4,5)P3
mediated calcium activation and/or sensitivity to Ins(1,4,5)P3. 2)
The studies also suggest considerable potential for maturational
modulation of pharmaco-mechanical coupling and homeostatic regulation
of cerebrovascular tone.
Received 19 January 1996; accepted in final form 14 May 1996.
APS Manuscript Number H44-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96