Maturation enhances fluid shear-induced activation of eNOS in perfused ovine carotid arteries

White, Charles R.; Hamade, Mohammad Wael; Siami, Koushan; Chang, Melody; Mangalwadi, Anandit; Frangos, John A.; Pearce, William J.

doi:10.1152/ajpheart.01013.2004

Cited by 18 publications

(18 citation statements)

References 35 publications

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“…Statin treatment can also increase NO bioavailability in fetal sheep, most probably through an increased capacity for NO synthesis [221]. Equally important, the capacity for NO synthesis and release in most vascular beds increases with developmental age [222, 223], which helps explain certain age-related differences in reactivity to endothelium-dependent vasodilators [224] but also predicts that the role of NO in vascular remodeling strengthens with advancing postnatal age.…”

Section: Receptor Tyrosine Kinase-independent Vasotrophic Factorsmentioning

confidence: 99%

Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling

Silpanisong¹,

Pearce²

2013

CVP

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Hypoxia can induce functional and structural vascular remodeling by changing the expression of trophic factors to promote homeostasis. While most experimental approaches have been focused on functional remodeling, structural remodeling can reflect changes in the abundance and organization of vascular proteins that determine functional remodeling. Better understanding of age-dependent hypoxic macrovascular remodeling processes of the cerebral vasculature and its clinical implications require knowledge of the vasotrophic factors that influence arterial structure and function. Hypoxia can affect the expression of transcription factors, classical receptor tyrosine kinase factors, non-classical G-protein coupled factors, catecholamines, and purines. Hypoxia’s remodeling effects can be mediated by Hypoxia Inducible Factor (HIF) upregulation in most vascular beds, but alterations in the expression of growth factors can also be independent of HIF. PPARγ is another transcription factor involved in hypoxic remodeling. Expression of classical receptor tyrosine kinase ligands, including vascular endothelial growth factor, platelet derived growth factor, fibroblast growth factor and angiopoietins, can be altered by hypoxia which can act simultaneously to affect remodeling. Tyrosine kinase-independent factors, such as transforming growth factor, nitric oxide, endothelin, angiotensin II, catecholamines, and purines also participate in the remodeling process. This adaptation to hypoxic stress can fundamentally change with age, resulting in different responses between fetuses and adults. Overall, these mechanisms integrate to assure that blood flow and metabolic demand are closely matched in all vascular beds and emphasize the view that the vascular wall is a highly dynamic and heterogeneous tissue with multiple cell types undergoing regular phenotypic transformation.

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Section: Receptor Tyrosine Kinase-independent Vasotrophic Factorsmentioning

confidence: 99%

Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling

Silpanisong¹,

Pearce²

2013

CVP

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“…One may consider the data per unit of eNOS to understand the sensitivity of the enzyme. 32 Since eNOS was not measured in this study, this remains to be explored in the future. An alternative approach may be to evaluate the measure based on density of endothelial cells; i.e., the number of endothelial cells per intimal layer.…”

Section: Study Limitationsmentioning

confidence: 98%

Relation of Nitrite to Structural and Mechanical Adaptation of Arteries During Postnatal Development

2008

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Mammalian arteries undergo rapid remodeling during postnatal growth and development. The high wall shear stress at birth is an important mediator of postnatal endothelial nitric oxide (NO) and consequently of growth and remodeling. The objective of this study was to quantify the NO production in relation to geometric and mechanical remodeling of aorta and pulmonary artery during postnatal development. Fifty-one C57BL/6 mice aged from 1 to 33 days were divided into 8 age groups for measurements of nitrite (NO(x)). Systematic measurements of NO(x) in each rings were made in the main pulmonary artery and primary branch as well as along the length of aorta using the combination of a diazo coupling method and high-performance liquid chromatography. The NO(x) data on the aorta were correlated with data on the geometry (diameter, wall thickness) and mechanical properties (stress, strain, elastic modulus) in the same strain of mice under the same conditions. Our findings show postnatal age and vessel size affects the NO production; i.e., the NO(x) decreased with age and diameter. Furthermore, there is a significant positive correlation between strain and NO(x) but negative correlation between both wall thickness and elastic modulus and NO(x) levels. These findings suggest an important interplay between NO(x) and geometric and mechanical remodeling during postnatal growth and development.

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“…In perfused CCA from near-term fetal and adult sheep, White and colleagues demonstrated several aspects of NO synthesis [248]. eNOS abundance, when calculated in terms of endothelial surface area, was similar in the two age groups, as were mRNA levels.…”

Section: Vasorelaxation Pathways/responsesmentioning

confidence: 99%

“…When normalized relative to eNOS protein, the specific activity was considerably greater in adult than in fetal vessels. Similarly, the slope of the relation of eNOS specific activity to fluid shear stress was significantly greater in adult than fetal arteries [248] (Table 4 ). These results were reinforced by further studies demonstrating with maturation significant decrease in eNOS abundance, suggesting independent mechanisms for their regulation [247] (Table 4 ).…”

Section: Vasorelaxation Pathways/responsesmentioning

confidence: 99%

Cerebral Artery Signal Transduction Mechanisms: Developmental Changes in Dynamics and Ca<sup>2+</sup> Sensitivity

Longo¹,

Goyal²

2013

CVP

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As compared to the adult, the developing fetus and newborn infant are at much greater risk for dysregulation of cerebral blood flow (CBF), with complications such as intraventricular and germinal matrix hemorrhage with resultant neurologic sequelae. To minimize this dysregulation and its consequences presents a major challenge. Although in many respects the fundamental signal transduction mechanisms that regulate relaxation and contraction pathways, and thus cerebrovascular tone and CBF in the immature organism are similar to those of the adult, the individual elements, pathways, and roles differ greatly. Here, we review aspects of these maturational changes of relaxation/contraction mechanisms in terms of both electro-mechanical and pharmaco-mechanical coupling, their biochemical pathways and signaling networks. In contrast to the adult cerebrovasculature, in addition to attenuated structure with differences in multiple cytoskeletal elements, developing cerebrovasculature of fetus and newborn differs in many respects, such as a strikingly increased sensitivity to [Ca2+]i and requirement for extracellular Ca2+ for contraction. In essence, the immature cerebrovasculature demonstrates both “hyper-relaxation” and “hypo-contraction”. A challenge is to unravel the manner in which these mechanisms are integrated, particularly in terms of both Ca2+-dependent and Ca2+-independent pathways to increase Ca2+ sensitivity. Gaining an appreciation of these significant age-related differences in signal mechanisms also will be critical to understanding more completely the vulnerability of the developing cerebral vasculature to hypoxia and other stresses. Of vital importance, a more complete understanding of these mechanisms promises hope for improved strategies for therapeutic intervention and clinical management of intensive care of the premature newborn.

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Maturation enhances fluid shear-induced activation of eNOS in perfused ovine carotid arteries

Cited by 18 publications

References 35 publications

Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling

Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling

Relation of Nitrite to Structural and Mechanical Adaptation of Arteries During Postnatal Development

Cerebral Artery Signal Transduction Mechanisms: Developmental Changes in Dynamics and Ca<sup>2+</sup> Sensitivity

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