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

Zurcher, Shelley D; Ong-Veloso, Gleen L.; Akopov, Sergey E.; Pearce, William J.

doi:10.1159/000014028

Cited by 8 publications

(9 citation statements)

References 25 publications

(51 reference statements)

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“…Thus the reduction of contractile force during acute hypoxia does not seem to be caused by the release of EDRFs like NO, prostaglandins, and hyperpolarizing factors. This is in agreement with studies that demonstrate that the role of the endothelium in hypoxic relaxation only becomes evident in mature carotid and cerebral ovine arteries (48). Persistence of hypoxia-induced decrease of contraction in the presence of Bay-K8644 demonstrates that inactivation of voltage-operated Ca 2ϩ channels is not involved in the response either.…”

Section: Effects Of Acute Hypoxia On Contractionsupporting

confidence: 92%

“…32). The relative importance of these processes in arteries of chicken embryos is currently unknown but may be of interest to study because acute hypoxia has been shown to modulate the intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i )-force relationship (5,37,40) in adult mammalian arteries and may interfere with the ability of D-myo-inositol 1,4,5-trisphosphate to induce contraction in fetal arteries (2) and possibly with Ca 2ϩ handling in arteries of neonates (48). Studies in sheep suggest that fetal cerebral arteries display increased Ca 2ϩ sensitivity compared with those of the adult (20).…”

Section: Effects Of Acute Hypoxia On Contractionmentioning

confidence: 99%

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Direct effects of acute hypoxia on the reactivity of peripheral arteries of the chicken embryo

Ruijtenbeek

Kessels

Villamor

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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. Direct effects of acute hypoxia on the reactivity of peripheral arteries of the chicken embryo. Am J Physiol Regulatory Integrative Comp Physiol 283: R331-R338, 2002. First published April 4, 2002 10.1152/ajpregu.00675.2001.-In the chicken embryo, acute hypoxemia results in cardiovascular responses, including an increased peripheral resistance. We investigated whether local direct effects of decreased oxygen tension might participate in the arterial response to hypoxemia in the chicken embryo. Femoral arteries of chicken embryos were isolated at 0.9 of incubation time, and the effects of acute hypoxia on contraction and relaxation were determined in vitro. While hypoxia reduced contraction induced by high K ϩ to a small extent (Ϫ21.8 Ϯ 5.7%), contractile responses to exogenous norepinephrine (NE) were markedly reduced (Ϫ51.1 Ϯ 3.2%) in 80% of the arterial segments. This effect of hypoxia was not altered by removal of the endothelium, inhibition of NO synthase or cyclooxygenase, or by depolarization plus Ca 2ϩ channel blockade. When arteries were simultaneously exposed to NE and ACh, hypoxia resulted in contraction (ϩ49.8 Ϯ 9.3%). Also, relaxing responses to ACh were abolished during acute hypoxia, while the vessels became more sensitive to the relaxing effect of the NO donor sodium nitroprusside (pD2: 5.81 Ϯ 0.21 vs. 5.31 Ϯ 0.27). Thus, in chicken embryo femoral arteries, acute hypoxia blunts agonist-induced contraction of the smooth muscle and inhibits stimulated endothelium-derived relaxation factor release. The consequences of this for in vivo fetal hemodynamics during acute hypoxemia depend on the balance between vasomotor influences of circulating catecholamines and those of the endothelium.catecholamine; endothelium-derived relaxation factor IN THE FETUS, AN ACUTE DECREASE in arterial oxygen tension leads to cardiovascular responses, involving an elevation in blood pressure and redistribution of the cardiac output in favor of vital organs. In fetal lambs (10), fetal llamas (9), and chicken embryos (24, 25), increased levels of circulating catecholamines take part in this response. Early in gestation, the chromaffin cells in the primitive adrenal medulla are directly sensitive to low oxygen tension. Later in gestation, activation of efferent sympathetic nerves also contributes to the response (38). Antagonists of ␣-adrenoreceptors blunt the hypoxia-induced increase in fetal total peripheral resistance (9, 10, 25).Neurohumoral mechanisms have been proposed to be important regulators of blood flow in the hypoxemic fetus, but it remains to be established whether local and direct effects of decreased oxygen tension participate in the fetal cardiovascular response to hypoxemia. In previous studies, we have shown that chronic exposure to hypoxia affects both sympathetic innervation (34) and endothelium-dependent relaxation (33) of femoral arteries of the chicken embryo, but acute effects of hypoxia in isolated systemic arteries were not studied. Moreover, acute effects of low oxygen tension have been studied i...

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Section: Effects Of Acute Hypoxia On Contractionsupporting

confidence: 92%

Section: Effects Of Acute Hypoxia On Contractionmentioning

confidence: 99%

Direct effects of acute hypoxia on the reactivity of peripheral arteries of the chicken embryo

Ruijtenbeek

Kessels

Villamor

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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“…However, when NAME was added in the presence of indomethacin, the relation between pressure and diameter was shifted to significantly smaller diameters in both age groups. Consistent with reports of reduced endothelium-dependent vasodilator capacity (39) and reduced endothelial expression of eNOS (27) in immature compared with mature cerebral arteries, the vasoconstrictor effects of NAME were significantly greater in adult than in neonatal arteries (Fig. 2C).…”

Section: Effects Of Nos and Cox On Intrinsic Tonesupporting

confidence: 89%

Maturation depresses mouse cerebrovascular tone through endothelium-dependent mechanisms

Geary

Buchholz

Pearce

2003

American Journal of Physiology-Regulatory, Integrative and Comp

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Pearce. Maturation depresses mouse cerebrovascular tone through endothelium-dependent mechanisms. Am J Physiol Regul Integr Comp Physiol 284: R734-R741, 2003. First published December 5, 2002 10.1152/ajpregu.00510.2002In light of previous observations that the range of arterial pressures over which cerebral blood flow is autoregulated differs dramatically in neonates and adults, the present experiments explored the hypothesis that pressure-induced intrinsic arterial tone is regulated differently in neonatal and adult cerebral arteries. In cannulated and pressurized endothelium-intact mouse cerebral arteries Ͻ150 m in diameter, active intrinsic tone was evident at intraluminal pressures as low as 10 mmHg in neonatal arteries, but only at pressures of 60 mmHg or greater in adult arteries. Administration of 10 M indomethacin produced no significant effect on tone at any pressure in either neonatal or adult arteries, but subsequent addition of 100 M nitroarginine methyl ester (NAME) significantly vasoconstricted both neonatal and adult arteries at all pressures. Conversely, administration of 100 M NAME alone significantly vasoconstricted adult arteries only, and subsequent addition of 10 M indomethacin produced a significant additional vasoconstriction in adult arteries only, indicating an important interaction between the nitric oxide synthase and cyclooxygenase pathways, at least in adult arteries. In the presence of both indomethacin and NAME, intrinsic tone was significantly greater in neonatal than adult arteries, but when the endothelium was removed, tone was similar in neonatal and adult arteries at all pressures. Together, these results suggest that pressure-induced myogenic tone is regulated similarly in neonatal and adult mouse cerebral arteries but that the contribution of endothelial vasoactive factors to intrinsic tone is highly age dependent. neonatal mouse; myogenic tone; pressure; cerebral artery NOT LONG AFTER the establishment of the nitrous oxide method for measurement of human cerebral blood flow in the late 1950s, it was widely recognized that cerebral perfusion was regulated independent of arterial pressure between pressures of Ϸ60 and Ϸ160 mmHg (22,25,37). This pattern of regulation, termed "cerebral autoregulation," has since been the focus of more than 2,600 studies that together indicate involvement of multiple different mechanisms in this response.Most important among these are the myogenic mechanisms that transduce changes in intraluminal hydraulic pressure and/or vascular wall stresses into changes in vascular smooth muscle contractility (10, 16). Release of vasoactive substances from the vascular endothelium in response to changes in shear stress also undoubtedly contributes to cerebrovascular autoregulatory adjustments (13). In addition, autonomic neurovascular mechanisms can potently influence the arterial pressure range over which cerebral autoregulation is effective (6).Owing to the central role of cerebral autoregulation for maintenance of cerebrovascular homeostasis, insults tha...

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“…Whereas acute hypoxia clearly had the capacity to relax isolated fetal cerebral arteries [60] through endothelium-independent mechanisms [61], chronic hypoxia dramatically altered the structure and contractility of both fetal and adult cerebral arteries and attenuated the vasodilator efficacy of NO [62, 63]. In relation to norepinephrine, hypoxia also decreased adrenergic receptor density and NE-induced IP3 mobilization [64], but upregulated pre-synaptic adrenergic reactivity while simultaneously depressing post-synaptic adrenergic reactivity [65].…”

Section: The 1990s: Growing Interest In Fetal Cerebral Vascular Biomentioning

confidence: 99%

The Fetal Cerebral Circulation: Three Decades of Exploration by the LLU Center for Perinatal Biology

Pearce

2014

Advances in Fetal and Neonatal Physiology

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For more than three decades, research programs in the Center of Perinatal Biology have focused on the vascular biology of the fetal cerebral circulation. In the 1980s, research in the Center demonstrated that cerebral auto-regulation operated over a narrower pressure range, and was more vulnerable to insults, in fetuses than in adults. Other studies were among the first to establish that compared to adult cerebral arteries, fetal cerebral arteries were more hydrated, contained smaller smooth muscle cells and less connective tissue, and had endothelium less capable of producing NO. Work in the 1990s revealed that pregnancy depressed reactivity to NO in extra-cerebral arteries, but elevated it in cerebral arteries through effects involving changes in cGMP metabolism. Comparative studies verified that fetal lamb cerebral arteries were an excellent model for cerebral arteries from human infants. Biochemical studies demonstrated that cGMP metabolism was dramatically upregulated, but that contraction was far more dependent on calcium influx, in fetal compared to adult cerebral arteries. Further studies established that chronic hypoxia accelerates functional maturation of fetal cerebral arteries, as indicated by increased contractile responses to adrenergic agonists and perivascular adrenergic nerves. In the 2000s, studies of signal transduction established age-dependent roles for PKG, PKC, PKA, ERK, ODC, IP3, myofilament calcium sensitivity, and many other mechanisms. These diverse studies clearly demonstrated that fetal cerebral arteries were functionally quite distinct compared to adult cerebral arteries. In the current decade, research in the Center has expanded to a more molecular focus on epigenetic mechanisms and their role in fetal vascular adaptation to chronic hypoxia, maternal drug abuse, and nutrient deprivation. Overall, the past three decades have transformed thinking about, and understanding of, the fetal cerebral circulation due in no small part to the sustained research efforts by faculty and staff in the Center for Perinatal Biology.

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

Cited by 8 publications

References 25 publications

Direct effects of acute hypoxia on the reactivity of peripheral arteries of the chicken embryo

Direct effects of acute hypoxia on the reactivity of peripheral arteries of the chicken embryo

Maturation depresses mouse cerebrovascular tone through endothelium-dependent mechanisms

The Fetal Cerebral Circulation: Three Decades of Exploration by the LLU Center for Perinatal Biology

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