Maturation Modulates Serotonin- and Potassium-Induced Calcium-45 Uptake in Ovine Carotid and Cerebral Arteries

Zurcher, Shelley D; Pearce, William J.

doi:10.1203/00006450-199510000-00004

Cited by 20 publications

(18 citation statements)

References 39 publications

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“…In light of observations that hypoxia produces vasodilation at least in part by inhibiting calcium influx [2,19,22], this latter finding suggests that hypoxia more effectively inhibits calcium influx in neonatal than in adult arteries. This interpretation is reinforced by previous findings that neonatal arteries are more dependent on extracellular than on intracellular sources of calcium for the initiation and maintenance of contraction [32]. Interestingly, however, reductions in extracellular calcium concentration enhanced the magnitude of hypoxic relaxation more in adult than in newborn denuded arteries (fig.…”

Section: Discussionsupporting

confidence: 67%

Maturational Modification of Hypoxic Relaxation in Ovine Carotid and Cerebral Arteries: Role of Endothelium

Zurcher¹,

Ong-Veloso²,

Akopov³

et al. 1998

Neonatology

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In light of evidence that hypoxia inhibits cerebrovascular calcium influx and that the contractile importance of calcium influx is greater in neonatal than adult cerebral arteries, the present studies evaluate the hypothesis that the mechanisms involved in hypoxic cerebral vasodilation are different in newborn and adult cerebral arteries. Intact segments of ovine common carotid (COM) and middle cerebral (MCA) arteries from 3- to 7-day-old newborn lambs and nonpregnant adults were mounted in tissue baths, contracted with 1 µM 5-HT, and exposed to hypoxia for 20 min (P_O2 ≈ 12 Torr). In endothelium-intact arteries, the magnitude of relaxation was similar and near maximal in all groups (range 82–92%) and did not vary with either age or artery type. However, the magnitude of hypoxic relaxation after endothelium removal was attenuated more in adult (COM 37 ± 6%, MCA 53 ± 7%) than in newborn (COM 75 ± 5%, MCA 93 ± 1%) arteries. In addition, endothelium-dependent responses to A23187, which like hypoxia increases endothelial cell concentrations of calcium, were attenuated in immature compared to mature arteries. Reductions of extracellular calcium concentration from 1.6 to 0.8 mM eliminated all age-dependent differences in relaxation responses to hypoxia. Together these data demonstrate that in newborn arteries, the endothelium-dependent component of hypoxic vasodilation is minimal, especially in intracerebral arteries, and robust relaxant responses to hypoxia depend on the high sensitivity of immature smooth muscle cells to decreases in P_O2. In contrast, in adult arteries the smooth muscle sensitivity to decreases in P_O2 is minimal and the endothelial component of hypoxic relaxation is particularly important in responses to hypoxia.

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Section: Discussionsupporting

confidence: 67%

Maturational Modification of Hypoxic Relaxation in Ovine Carotid and Cerebral Arteries: Role of Endothelium

Zurcher¹,

Ong-Veloso²,

Akopov³

et al. 1998

Neonatology

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“…In several tissues, Ca 2ϩ influx has been shown to vary with developmental age. In cerebral arteries, KCl-dependent contraction was also reduced, but the L-type Ca 2ϩ channel contribution to agonist-induced contraction and Ca 2ϩ mobilization in fetal and newborn smooth muscle cells was higher than in the adult (24,43). Similarly, the neonatal myocardium is much more dependent on transmembrane Ca 2ϩ influx and less dependent on Ca 2ϩ release from intracellular storage sites than the adult myocardium (8,21).…”

Section: Discussionmentioning

confidence: 86%

Developmental changes in Ca²⁺ homeostasis and contractility in gallbladder smooth muscle

Camello-Almaraz¹,

Macias²,

Gomez‐Pinilla³

et al. 2009

American Journal of Physiology-Cell Physiology

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Relatively little is known about the contribution of Ca(2+)-dependent and -independent mechanisms in the contractility of neonatal gastrointestinal smooth muscle. We therefore studied Ca(2+) homeostasis and Ca(2+) sensitization mechanisms in 10-day-old and adult guinea pig gallbladder smooth muscle to elucidate developmental changes in these processes. Gallbladder contractility was evaluated by isometrical tension recordings from strips, intracellular Ca(2+) concentration was estimated by epifluorescence microscopy of fura-2-loaded isolated cells, and protein expression and phosphorylation were assessed by Western blot analysis. The neonatal gallbladder contracted significantly less to CCK than adult tissue, but this correlated with an increased Ca(2+) mobilization, suggesting immaturity of Ca(2+) sensitization mechanisms. The enhanced Ca(2+) release in the newborn gallbladder was the result of the increase in the size of the releasable Ca(2+) pool. Moreover, in neonatal smooth muscle cells, neither the plasma membrane Ca(2+) pump nor the Na(+)/Ca(2+) exchanger collaborate in the extrusion of Ca(2+). In contrast, in these cells, there is an increase in phospholamban phosphorylation, which could drive to an overactivity of the sarco(endo)plasmic reticulum Ca(2+)-ATPase pump. The reduced Ca(2+) sensitivity in neonatal tissues was demonstrated by the lack of effect to Y-27362, an inhibitor of Rho kinase (ROCK), and GF-109203X, an inhibitor of PKC, on agonist-induced contraction. In addition, the neonatal gallbladder showed lower levels of RhoA, ROCK, PKC, and two effectors [C-kinase-dependent inhibitor of 17 kDa (CPI-17) and myosin phosphatase targetting 1 (MYPT1)] as well as an absence of CPI-17 and MYPT1 phosphorylation in response to agonists. In conclusion, our results indicate that the main mechanisms involved in smooth muscle contractility are under developmental regulation.

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“…These findings also suggest the possibility that increased calcium sensitivity may in some way offset the greater dependence on extracellular calcium [33] and lower content of sarcoplasmic reticulum [34] characteristic of small, compared to large, arteries. From this perspective, the transition from small to large arteries may be associated with a parallel shift from dependence on increases in calcium sensitivity to increases in calcium concentration during the development of contractile tone.…”

Section: Discussionmentioning

confidence: 85%

Developmental Changes in the Calcium Sensitivity of Rabbit Cranial Arteries

Akopov

Zhang

Pearce³

1998

Neonatology

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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.

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Maturation Modulates Serotonin- and Potassium-Induced Calcium-45 Uptake in Ovine Carotid and Cerebral Arteries

Cited by 20 publications

References 39 publications

Maturational Modification of Hypoxic Relaxation in Ovine Carotid and Cerebral Arteries: Role of Endothelium

Maturational Modification of Hypoxic Relaxation in Ovine Carotid and Cerebral Arteries: Role of Endothelium

Developmental changes in Ca²⁺ homeostasis and contractility in gallbladder smooth muscle

Developmental Changes in the Calcium Sensitivity of Rabbit Cranial Arteries

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Maturation Modulates Serotonin- and Potassium-Induced Calcium-45 Uptake in Ovine Carotid and Cerebral Arteries

Cited by 20 publications

References 39 publications

Maturational Modification of Hypoxic Relaxation in Ovine Carotid and Cerebral Arteries: Role of Endothelium

Maturational Modification of Hypoxic Relaxation in Ovine Carotid and Cerebral Arteries: Role of Endothelium

Developmental changes in Ca2+ homeostasis and contractility in gallbladder smooth muscle

Developmental Changes in the Calcium Sensitivity of Rabbit Cranial Arteries

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Product

Resources

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Developmental changes in Ca²⁺ homeostasis and contractility in gallbladder smooth muscle