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• W2076403322 abstract "Accumulating evidence suggests that extracellular signal‐regulated kinases (ERK1/2) play a key role in regulating vascular tone. To test the hypotheses that ERK1/2 modulate cerebral artery agonist‐induced contraction, and that this changes with developmental age, we measured both total and phosphorylated ERK1/2 in adult and fetal ovine cerebral arteries. In middle cerebral arteries (MCA) we also examined tension and [Ca 2+ ] i responses to phenylephrine (PHE), in the absence and presence of the ERK1/2 inhibitor U‐0126 and the mitogen‐activated protein kinase kinase (MAPKK or MEK) inhibitor PD‐98059. In the fetus, but not adult, U‐0126 potentiated PHE‐induced contraction. In both age groups, inhibition by U‐0126, but not PD‐98059, decreased the PHE‐induced [Ca 2+ ] i increase; in fact for adult, this eliminated any significant [Ca 2+ ] i increase. In turn in the adult, but not fetus, protein kinase C (PKC) inhibition by staurosporine (3 × 10 −8 M) prior to ERK1/2 inhibition by U‐0126 (10 −5 M) prevented this elimination of [Ca 2+ ] i increase. In adult and fetal cerebral arteries basal total ERK1/2 levels were similar. However, in fetal arteries the basal phosphorylated ERK1/2 levels were significantly less than in adult. In fetal, but not adult, cerebral arteries, 10 −6 ‐10 −4 m PHE increased ERK1/2 phosphorylation in a concentration‐ and time‐dependent manner. The ERK1/2 inhibitor U‐0126, but not the MEK inhibitor PD‐98059, lowered basal activated ERK1/2 levels in vessels of both age groups. These results suggest that basal levels of phosphorylated ERK1/2 play an important role in suppressing Ca 2+ sensitivity, perhaps by PKC inhibition. The developmental increase in cerebral artery basal phosphorylated ERK levels from fetus to adult, suggests a transition in the regulation of contraction from Ca 2+ sensitivity in the fetal arteries to Ca 2+ concentration in the adult vessels." @default.
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• W2076403322 date "2003-09-01" @default.
• W2076403322 modified "2023-10-18" @default.
• W2076403322 title "Extracellular Signal‐Regulated Kinases and Contractile Responses in Ovine Adult and Fetal Cerebral Arteries" @default.
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• W2076403322 doi "https://doi.org/10.1113/jphysiol.2003.046128" @default.
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