Developmental Changes in the Calcium Sensitivity of Rabbit Cranial Arteries

Abstract

The present experiments examine developmental changes in cerebrovascular Ca²⁺ sensitivity. Common carotid (COM), basilar (BAS) and femoral (FA) arteries from adult (n = 16), 8- to 9-day-old (n = 15) and 24- to 25-day-old rabbits (n = 12) were denuded of the endothelium and permeabilized with β-escin. Bath calcium concentrations were controlled via EGTA-Ca²⁺ buffer solutions. Adult pCa-force relations were right-shifted relative to those of 8- to 9-day-old rabbits but were similar to those of 24- to 25-day-olds. Adult pD₂ (–log ED₅₀) values for Ca²⁺ averaged 6.36 ± 0.03 (COM), 6.77 ± 0.04 (BAS) and 6.40 ± 0.04 (FA). Corresponding 8- to 9-day-old values were 6.85 ± 0.03, 7.08 ± 0.08 and 6.76 ± 0.05. In all arteries studied, the addition of 5-hydroxytryptamine (5-HT) subsequent to contraction by a constant submaximal (EC₃₀) concentration of Ca²⁺ produced a dose-dependent and GDPβS-sensitive increase in tension attributable to an increase in Ca²⁺ sensitivity. The magnitudes of 5-HT-induced increases in Ca²⁺ sensitivity were significantly greatest in 8- to 9-day-old rabbits, intermediate in 24- to 25-day-old rabbits, and least in adults. GTPγS mimicked the effects of 5-HT and prevented further increases in Ca²⁺ sensitivity induced by 5-HT in all arteries from all age groups. GDPβS completely reversed all effects of 5-HT on Ca²⁺ sensitivity. From these data we conclude that baseline Ca²⁺ sensitivity is elevated in newborn relative to adult rabbits, at least in femoral, common carotid and basilar arteries. In these arteries, 5-HT can increase Ca²⁺ sensitivity via a G-protein-dependent mechanism which is more effective in neonatal than adult arteries. These effects of maturation on vascular Ca²⁺ sensitivity may play an important role in developmental changes in vascular reactivity.