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.

Trophic action of sympathetic nerves reduces arterial smooth muscle Ca2+sensitivity during early post-natal development in rats

“…These findings are supported by earlier reports and extend them to a vascular bed not studied before. Such a change of Ca 2+ sensitivity has been observed in ovine and rabbit cerebral arteries (Akopov et al 1997, Sandoval et al 2007), rat portal vein (Bruce & Nixon 1997), rabbit elastic-type femoral artery (Akopov et al 1998) and some other vascular preparations. However, we show here, for the first time, that a greater Ca 2+ sensitivity is also typical for developing muscular-type arteries from the peripheral circulation.…”

Maturation depresses mouse cerebrovascular tone through endothelium-dependent mechanisms

“…Some postnatal changes involve shifts in artery hydration, protein content, and structure, whereas others affect receptor density, calcium metabolism, or endothelial function (1,29,30,33). Much of what is known about the vascular consequences of postnatal maturation, however, has been learned through studies of large resistance-sized cerebral arteries with diameters greater than 350 m. Arteries smaller than 150 m in diameter also contribute to vascular resistance and blood flow distribution but have yet to be examined in vitro from neonatal animals.…”

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). Postnatal maturation also modulates the types and populations of receptors expressed in cerebral arteries (26,47) and enhances reactivity to stimulation of perivascular adrenergic nerves (37).…”