title: Chronic hypoxia modulates relations among calcium, myosin light chain phosphorylation, and force differently in fetal and adult ovine basilar arteries.
abstract: The present study tests the hypothesis that age-related differences in contractility of cerebral arteries from hypoxic animals involve changes in myofilament Ca2+ sensitivity. Basilar arteries from term fetal and nonpregnant adult sheep maintained 110 days at 3,820 m were used in measurements of cytosolic calcium concentration ([Ca2+]i), myosin light chain phosphorylation, and contractile tensions induced by graded concentrations of K+ or serotonin (5-HT). Slopes relating [Ca2+]i to tension were similar in fetal (0.83 +/- 0.07) and adult (1.02 +/- 0.08) arteries for K+ contractions but were significantly greater for fetal (3.77 +/- 0.64) than adult (2.00 +/- 0.13) arteries for 5-HT contractions. For both K+ and 5-HT contractions, these relations were left shifted in fetal compared with adult arteries, indicating greater Ca2+ sensitivity in fetal arteries. In contrast, slopes relating [Ca2+]i and %myosin phosphorylation for K+ contractions were less in fetal (0.37 +/- 0.08) than adult (0.81 +/- 0.07) arteries, and the fetal curves were right shifted. For 5-HT contractions, the slope of the Ca2+-phosphorylation relation was similar in fetal (0.33 +/- 0.09) and adult (0.33 +/- 0.23) arteries, indicating that 5-HT depressed Ca2+-induced myosin phosphorylation in adult arteries. For slopes relating %myosin phosphorylation and tension, fetal values (K+: 1.52 +/- 0.22, 5-HT: 7.66 +/- 1.70) were less than adult values (K+: 2.13 +/- 0.30, 5-HT: 8.29 +/- 2.40) for both K+- and 5-HT-induced contractions, although again fetal curves were left shifted relative to the adult. Thus, in hypoxia-acclimatized basilar arteries, a downregulated ability of Ca2+ to promote myosin phosphorylation is offset by an upregulated ability of phosphorylated myosin to produce force yielding an increased fetal myofilament Ca2+ sensitivity. Postnatal maturation reprioritizes the mechanisms regulating hypoxic contractility through changes in the source of activator Ca2+, the pathways governing myosin light chain phosphorylation, and its interaction with actin.
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Surya M
authors.initials: SM
authors.lastname: Nauli
authors.forename: James M
authors.initials: JM
authors.lastname: Williams
authors.forename: William T
authors.initials: WT
authors.lastname: Gerthoffer
authors.forename: William J
authors.initials: WJ
authors.lastname: Pearce
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000375:Aging; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000196:embryology* / Q000503:physiopathology*; D002118:Calcium / Q000494:pharmacology*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000196:embryology / Q000503:physiopathology; D018994:Myosin Light Chains / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012756:Sheep; D013223:Statistics as Topic; D013314:Stress, Mechanical
chemical_list: D018994:Myosin Light Chains; D002118:Calcium