Nauli, S.M., Williams, J.M., Gerthoffer, W.T., Pearce. W.J.. "Chronic Hypoxia Modulates Relations Among Calcium, Myosin Light Chain Phosphorylation, and Force Differently in Fetal and Adult Ovine Basilar Arteries." Journal of Applied Physiology 99. (2005): 120-127. ( 1/2005 )
The present study tests the hypothesis that age-related differences in the contractility of cerebral arteries from hypoxic animals involve changes in myofilament Ca++ sensitivity. Basilar arteries from term fetal and non-pregnant adult sheep maintained 110 days at 3820 m were used for measurements of [Ca++]i, myosin light chain phosphorylation, and contractile tensions induced by graded concentrations of K+ or 5HT. Slopes relating [Ca++]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 5HT-contractions. For both K+ and 5HT- contractions, these relations were left-shifted in fetal compared to adult arteries, indicating greater Ca++ sensitivity in fetal arteries. In contrast, slopes relating [Ca++]i to %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 5HT-contractions the slope of the [Ca++]i-phosphorylation relation was similar in fetal (0.33±0.09) and adult (0.33±0.23) arteries, indicating that 5HT depressed [Ca++]i-induced myosin phosphorylation in adult arteries. For slopes relating %myosin phosphorylation to tension, fetal values (K+:1.52±0.22, 5HT:7.66±1.70) were less than adult values (K+:2.13±0.30, 5HT:8.29±2.40) for both K+ and 5HT-induced contractions, although again fetal curves were left-shifted relative to the adult. Thus, in hypoxia-acclimatized basilar arteries, a downregulated ability of Ca++ to promote myosin phosphorylation is offset by an upregulated ability of phosphorylated myosin to produce force yielding an increased fetal myofilament Ca++ sensitivity. Postnatal maturation reprioritizes the mechanisms regulating hypoxic contractility through changes in the source of activator Ca++, the pathways governing myosin light chain phosphorylation, and its interaction with actin.