Maturation Alters the Contractile Role of Calcium in Ovine Basilar Arteries

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.

Postnatal maturation attenuates pressure-evoked myogenic tone and stretch-induced increases in Ca2+in rat cerebral arteries

“…For example, initiation and maintenance of contraction is much more dependent on calcium influx in cerebral arteries of the fetus than those of the adult (3). In parallel, fetal cerebral arteries also exhibit greater augmentation of agonist-induced myofilament calcium sensitization than observed in corresponding adult arteries (2,4,5).…”

Fetal cerebrovascular acclimatization responses to high-altitude, long-term hypoxia: a model for prenatal programming of adult disease?

“…For many vessels, including cerebral arteries (51,55), calcium entry through L-type Ca 2ϩ channels constitutes the main fraction of contractile calcium, owing to sparse or poorly developed sarcoplasmic reticulum. This is particularly true for immature cerebral arteries, which are essentially totally dependent on Ca 2ϩ influx through L-type Ca 2ϩ channels for contraction (1,41,44).…”

Resuscitation of the Meconium-Stained Infant and Prevention of Meconium Aspiration Syndrome

“…Neonatal pulmonary vessels are known to exhibit greater vasoconstrictive responses than adult pulmonary arteries. 46 In addition, these vessels possess a unique ability to undergo rapid changes in architecture, particularly thickening of the media and the adventitia, distal extension of smooth muscle, 47 and increased tortuosity and muscularization of the alveolar septal arterioles. 48 The importance of this abnormal proliferation and excessive collagen synthesis by pulmonary vascular wall cells has been demonstrated by attenuation of the pulmonary hypertensive process by inhibitors of collagen synthesis in a rat model.…”