Ontogeny of Vascular Smooth
Muscle Responsiveness in the
Postweaning Rat

Soltis, Edward E.; Newman, Pamela S.

doi:10.1159/000480597

Cited by 7 publications

(3 citation statements)

References 16 publications

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“…That fetal cerebral arteries responded in such a desultory fashion to transmural nerve stimulation agrees with observations that such responses increase with maturation [7]. This contrasts, however, with reports of the opposite trend in ovine pial [215], monkey basilar and middle cerebral [49], canine coronary [216], and mesenteric [219], ovine renal [217, 220], and rat tail [221] arteries. Also in newborn piglets, denervation of the superior sympathetic ganglion was associated with a loss of autoregulation, CBF becoming pressure dependent [222].…”

Section: Neuroeffector Mechanismssupporting

confidence: 75%

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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Section: Neuroeffector Mechanismssupporting

confidence: 75%

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

Longo¹,

Goyal²

2013

CVP

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“…Endothelium-dependent relaxation mediated by Ach has been reported to fall during rat maturation (Soltis and Newman, 1992 ). Our study corroborates that relaxation decreases with age and this response is more pronounced in males.…”

Section: Discussionmentioning

confidence: 99%

Age-, Gender-, and in Vivo Different Doses of Isoproterenol Modify in Vitro Aortic Vasoreactivity and Circulating VCAM-1

et al. 2018

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Different human-like cardiomyopathies associated to β-adrenergic stimulation are experimentally modeled in animals through variations in dose, route, and duration of administration of different cardiotoxic drugs. However, associated changes in the vasculature and their relation to systemic inflammation, and the influence of cardiovascular diseases risk factors (gender and age) upon them are seldom analyzed. Here we studied the effect of age and gender on the vasoreactivity of aortas from mice subjected to in vivo repeated β-adrenergic stimulation with different doses of isoproterenol (ISO) in association with circulating inflammatory cytokines. Young (2 months) and old (18 months) male and female mice received 0 (control), 5, 40, 80 or 160 μg/g/d of ISO (7 days, s.c.). IL-1α, IL-4 and vascular cell adhesion molecule-1 (VCAM-1) were quantified in plasma. In vitro, norepinephrine-induced vasoconstriction and acetylcholine-induced relaxation were measured in aortas. No differences in contraction, relaxation, IL-1α, and IL-4 were found between control young males and females. Age decreased contraction in males and relaxation was lower in females and abolished in males. VCAM-1 was higher in young males than in females and increased in old mice. Vasoconstriction in ISO-treated mice results as a bell-shaped curve on contraction in young and old males, with lower values in the latter. In females, ISO-160 increased contraction in young females but decreased it in old females. Vasorelaxation was reduced in ISO-treated young males and females. ISO-80 and 160 reduced vasorelaxation in old females, and intermediate doses relaxed aortas from old males. VCAM-1 was higher in young and old males with ISO-80 and 160; while VCAM-1 was higher only with ISO-160 in old females. Our results demonstrate that repeated β-adrenergic stimulation modifies vascular reactivity depending on gender, age, and dose. Females were less sensitive to alterations in vasoreactivity, and young females required a higher amount of the adrenergic stimuli than old females to show vascular alterations. Changes were independent of IL-1α and IL-4. VCAM-1 only changed in old females stimulated with ISO 160. Our results highlight the relevance of considering and comparing in the same study females and aged organisms to improve the accuracy of applications to clinical studies.

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“…The contractile responses of vascular smooth muscle to norepinephrine, KCl, 5-hydroxytryptamine, electro-stimulation and calcium-free physiological solution are increased during development and maturity in normal rats. Endothelium-dependent relaxation mediated by acetylcholine as well as isoproterenol, which is mediated by the β-receptor, falls during rat maturation [104].…”

Section: Aging and Hypertensionmentioning

confidence: 95%

Metabolic Syndrome: Early Development and Aging

Guarner¹,

Esther²

2012

J Diabetes Metab

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Adult metabolic and heart diseases have their origin early during intrauterine development and childhood. They can be traced to the inherited genome but patterns of cellular gene expression appropriate to the environment during development (epigenetics) also play an important role. This is particularly important during critical periods of time where structural and functional changes known as critical windows. There is a critical window of the pancreas when, if changes in diet occur, the risk of metabolic diseases during adulthood increases. Aging is defined as a series of morphological and functional changes which take place over time. The term also refers to the deterioration of the biological functions after an organism has attained its maximum reproductive potential. The aging process is altered or accelerated when cardio-metabolic diseases are present but also aging makes organisms more susceptible to such ills. The same genes and proteins that might undergo epigenetic changes that predispose to metabolic diseases in the adult, also participate in the acceleration of aging with metabolic syndrome. Aging predisposes to metabolic syndrome, type-2 diabetes or insulin resistance; however, other predisposing conditions such as obesity, inflammation, changes in the activity of the hypothalamus-hypophysis suprarenal axis and in the activity of the autonomous nervous system, hypertension, also contribute to increase its prevalence. J ou rna l o f D ia be tes & M e ta bolism

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Ontogeny of Vascular Smooth Muscle Responsiveness in the Postweaning Rat

Cited by 7 publications

References 16 publications

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

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

Age-, Gender-, and in Vivo Different Doses of Isoproterenol Modify in Vitro Aortic Vasoreactivity and Circulating VCAM-1

Metabolic Syndrome: Early Development and Aging

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