Dataset Information

Developmental Maturation and Alpha-1 Adrenergic Receptors-Mediated Gene Expression Changes in Ovine Middle Cerebral Arteries.

ABSTRACT: The Alpha Adrenergic Signaling Pathway is one of the chief regulators of cerebrovascular tone and cerebral blood flow (CBF), mediating its effects in the arteries through alpha1-adrenergic receptors (Alpha1AR). In the ovine middle cerebral artery (MCA), with development from a fetus to an adult, others and we have shown that Alpha1AR play a key role in contractile responses, vascular development, remodeling, and angiogenesis. Importantly, Alpha1AR play a significant role in CBF autoregulation, which is incompletely developed in a premature fetus as compared to a near-term fetus. However, the mechanistic pathways are not completely known. Thus, we tested the hypothesis that as a function of maturation and in response to Alpha1AR stimulation there is a differential gene expression in the ovine MCA. We conducted microarray analysis on transcripts from MCAs of premature fetuses (96-day), near-term fetuses (145-day), newborn lambs, and non-pregnant adult sheep (2-year) following stimulation of Alpha1AR with phenylephrine (a specific agonist). We observed several genes which belonged to pro-inflammatory and vascular development/angiogenesis pathway significantly altered in all of the four age groups. We also observed age-specific changes in gene expression-mediated by Alpha1AR stimulation in the different developmental age groups. These findings imply complex regulatory mechanisms of cerebrovascular development.

SUBMITTER: Goyal D

PROVIDER: S-EPMC5789090 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Developmental Maturation and Alpha-1 Adrenergic Receptors-Mediated Gene Expression Changes in Ovine Middle Cerebral Arteries.

Goyal Dipali D Goyal Ravi R

Scientific reports 20180129 1

The Alpha Adrenergic Signaling Pathway is one of the chief regulators of cerebrovascular tone and cerebral blood flow (CBF), mediating its effects in the arteries through alpha1-adrenergic receptors (Alpha1AR). In the ovine middle cerebral artery (MCA), with development from a fetus to an adult, others and we have shown that Alpha1AR play a key role in contractile responses, vascular development, remodeling, and angiogenesis. Importantly, Alpha1AR play a significant role in CBF autoregulation, w ...[more]

PMID: 29379105

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Project description:Epidemiological studies demonstrate that there are sex differences in the incidence, prevalence, and outcomes of cerebrovascular disease (CVD). The present study compared the structure and composition of the middle cerebral artery (MCA), neurovascular coupling, and cerebrovascular function and cognition in young Sprague-Dawley (SD) rats. Wall thickness and the inner diameter of the MCA were smaller in females than males. Female MCA exhibited less vascular smooth muscle cells (VSMCs), diminished contractile capability, and more collagen in the media, and a thicker internal elastic lamina with fewer fenestrae compared with males. Female MCA had elevated myogenic tone, lower distensibility, and higher wall stress. The stress/strain curves shifted to the left in female vessels compared with males. The MCA of females failed to constrict compared with a decrease of 15.5?±?1.9% in males when perfusion pressure was increased from 40 to 180 mmHg. Cerebral blood flow (CBF) rose by 57.4?±?4.4 and 30.1?±?3.1% in females and males, respectively, when perfusion pressure increased from 100 to 180 mmHg. The removal of endothelia did not alter the myogenic response in both sexes. Functional hyperemia responses to whisker-barrel stimulation and cognition examined with an eight-arm water maze were similar in both sexes. These results demonstrate that there are intrinsic structural differences in the MCA between sexes, which are associated with diminished myogenic response and CBF autoregulation in females. The structural differences do not alter neurovascular coupling and cognition at a young age; however, they might play a role in the development of CVD after menopause.NEW & NOTEWORTHY Using perfusion fixation of the middle cerebral artery (MCA) in calcium-free solution at physiological pressure and systematically randomly sampling the sections prepared from the same M2 segments of MCA, we found that there are structural differences that are associated with altered cerebral blood flow (CBF) autoregulation but not neurovascular coupling and cognition in young, healthy Sprague-Dawley (SD) rats. Understanding the intrinsic differences in cerebrovascular structure and function in males and females is essential to develop new pharmaceutical treatments for cerebrovascular disease (CVD).

Dataset Information

Developmental Maturation and Alpha-1 Adrenergic Receptors-Mediated Gene Expression Changes in Ovine Middle Cerebral Arteries.

Publications

Developmental Maturation and Alpha-1 Adrenergic Receptors-Mediated Gene Expression Changes in Ovine Middle Cerebral Arteries.

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