Maturation Alters the Contractile Role of Calcium in Ovine Basilar Arteries

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Abstract
The present studies examine how agonist-induced increases in cytosolic Ca2+ concentration and sensitivity vary with maturation. Basilar arteries from term fetal (138-141 d) and nonpregnant adult sheep were denuded of endothelium, mounted for measurements of contractile tension, and then loaded with Fura-2 to enable estimation of cytosolic Ca2+ responses to both potassium and serotonin (5-hydroxytryptamine, 5-HT). In response to potassium, normalized values of intracellular Ca2+ and tension increased in parallel in both fetal and adult preparations; no age-related differences were apparent. In contrast, 5-HT increased Ca2+ sensitivity significantly more in fetal than in adult arteries. In the absence of extracellular Ca2+, 5-HT increased cytosolic Ca2+ in adult but not fetal arteries. In addition, responses to repeated applications of 5-HT in the absence of extracellular Ca2+ were exhausted more rapidly in fetal than in adult arteries. We interpret these data to indicate that vascular maturation involves important shifts in the mechanisms mediating cerebrovascular pharmacomechanical coupling. Specifically, the data suggest that normal development involves a reduction in the Ca2+ sensitizing effects of agonists with parallel increases in the agonist-induced intracellular Ca2+ release. In so doing, these studies offer one possible reason why vascular reactivity varies dramatically with age. From a pathophysiologic perspective, these studies also advance the possibility that failure to shift from the increased Ca2+ sensitivity typical of immature arteries may lead to vascular hyperreactivity in adult arteries.