title: Developmental changes in alpha 1-adrenergic receptors, IP3 responses, and NE-induced contraction in cerebral arteries.
abstract: 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-ARs) and/or norepinephrine (NE)-induced inositol 1,4,5-trisphosphate [Ins(1,4,5)P3,IP3] synthesis, we quantified these variables and the NE-induced contraction in the common carotid artery (Com) and main branch cerebral arteries (MBC) from term fetal (approximately 140 gestational day) and newborn (2- to 5-day) sheep and compared them with adult values. In fetal and newborn Com, maximal contractions to NE (percent K+ maximum response) were 132 +/- 14 and 118 +/- 9%, respectively (adult = 92 +/- 7%). For fetal and newborn middle cerebral artery, these values were 34 +/- 10 and 43 +/- 7%, respectively (adult = 24 +/- 7%). alpha 1-AR density values in Com of fetal and newborn sheep were 113 +/- 18 and 106 +/- 4 fmol/mg protein, respectively (adult = 54 +/- 3 fmol/mg protein). For the MBC, density values were 47 +/- 2 and 24 +/- 3 fmol/mg protein, respectively (adult = 23 +/- 3 fmol/protein). In term fetal and newborn MBC, NE produced dose-dependent increases in Ins(1,4,5)P3, the maximal increases above basal values being 245 +/- 40 and 189 +/- 16%, respectively (adult = 254 +/- 35%). Neither fetus nor newborn Com showed significant Ins(1,4,5)P3 responses to NE. We concluded that in fetal and newborn Com and MBC, 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. The studies also suggest considerable potential for maturational modulation of pharmacomechanical coupling and homeostatic regulation of cerebrovascular tone.
authors.affiliation: Center for Perinatal Biology, Department of Physiology, Loma Linda University School of Medicine, California 92350, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: Longo
authors.forename: N
authors.initials: N
authors.lastname: Ueno
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: W J
authors.initials: WJ
authors.lastname: Pearce
authors.forename: L
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism / Q000502:physiology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D005314:Embryonic and Fetal Development; D005333:Fetus / Q000378:metabolism* / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012756:Sheep / Q000196:embryology; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D011942:Receptors, Adrenergic, alpha; D014662:Vasoconstrictor Agents; D015544:Inositol 1,4,5-Trisphosphate; D009638:Norepinephrine