Abstract
Neonatal vulnerability to intracranial hemorrhage is often attributed to a relative inability of immature cerebral arteries to contract. Because this depressed contractility may involve age-related differences in cerebrovascular calcium handling, the present study examined age-related differences in cerebral artery contractility and its dependence on extracellular calcium from 24 newborn lambs and 36 adult sheep. Contractile tensions and 45Ca uptakes were measured under baseline conditions and as a function of time during stimulation by both receptor-dependent (100 μM serotonin) and receptor-independent (122 mM K+) mechanisms of contraction in endothelium denuded newborn (N) and adult (A) ovine middle cerebral (MCA) and common carotid (COM) arteries. Maximum contractile responses to potassium averaged 4.5 ± 0.2 (N-COM), 5.8 ± 0.9 (A-COM), 3.0 ± 1.1 (N-MCA), and 3.1 ± 0.6 (A-MCA) g. Corresponding averages for responses to serotonin were 7.2 ± 0.8, 7.3 ± 1.1, 3.6 ± 0.1, and 3.6 ± 0.2; except for COM responses to potassium, contractile responses were little affected by maturation in either artery type. At baseline, uptakes averaged 0.39 ± 0.04 (N-MCA), 0.33 ± 0.04 (A-MCA), 0.25 ± 0.03 (N-COM), and 0.14 ± 0.01 (A-COM) μmol Ca/g dry weight/min. Maximum increases in calcium uptake produced by potassium depolarization averaged 231 ± 19% (N-MCA), 152 ± 13% (A-MCA), 156 ± 11% (N-COM), and 140 ± 14% (A-COM) above baseline. Corresponding increases produced by 100 μM serotonin averaged 201 ± 15% (N-MCA), 129 ± 23% (A-MCA), 143 ± 20% (N-COM), and 145 ± 18% (A-COM). Under all conditions examined, calcium uptakes were uniformly greater in newborn than adult arteries, and were greater in MCA than COM segments of the same age. For equivalent contractile tensions, newborn arteries required greater calcium uptakes than corresponding adult arteries. We attribute these differences largely to age-related variations in the activation of calcium entry through voltage-sensitive and receptor-operated membrane calcium channels.
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Zurcher, S., Pearce, W. Maturation Modulates Serotonin- and Potassium-Induced Calcium-45 Uptake in Ovine Carotid and Cerebral Arteries. Pediatr Res 38, 493–500 (1995). https://doi.org/10.1203/00006450-199510000-00004
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DOI: https://doi.org/10.1203/00006450-199510000-00004