Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 282, Issue 1, Pages R131-R138Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00318.2001
Keywords
cerebral circulation; norepinephrine; vascular smooth muscle; intracellular calcium; PN200-110; Bay K 8644; fetus; newborn
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Funding
- NICHD NIH HHS [HD/HL-03807, P01-HD-31226] Funding Source: Medline
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [P01HD031226, R01HD003807] Funding Source: NIH RePORTER
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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 H-3-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 (B-max) in the cerebral arteries, common carotid artery (CCA), and descending aortae of fetal (similar to 140 gestation days), newborn (7-10 days), and adult sheep. In the cerebral and common carotid arteries, B-max 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.
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