Endothelin-1 but not angiotensin II contributes to functional aging in murine carotid arteries

LIFE SCIENCES

卷:118

Article

Meyer, Matthias R.¹  Fredette, Natalie C.¹  Barton, Matthias²  Prossnitz, Eric R.¹ 

[1] Univ New Mexico, Hlth Sci Ctr, Dept Cell Biol & Physiol, Albuquerque, NM 87131 USA

[2] Univ Zurich, Zurich, Switzerland

关键词: Age;    Atherosclerosis;    Artery;    Cyclooxygenase;    Dementia;    GPCR;    gp91ds-tat;    NADPH;    Nox;    Oxidative stress;    Reactive oxygen species;    ROS;    Prostanoid;    Stroke;    Superoxide;    Vascular;   

DOI  :  10.1016/j.lfs.2014.02.027

来源: Elsevier

【 摘 要 】

Aims: Aging is a major risk factor for carotid artery disease and stroke. Endothelin-1 (ET-1) and angiotensin II (Ang II) are important modifiers of vascular disease, partly through increased activity of NADPH oxidase and vasoconstrictor prostanoids. Since the renin-angiotensin and endothelin systems become activated with age, we hypothesized that aging affects NADPH oxidase- and prostanoid-dependent contractions to ET-1 and Ang II. Main methods: Carotid artery rings of young (4 month-old) and old (24 month-old) C57BL6 mice were pretreated with the NO synthase inhibitor L-NAME to exclude differential effects of NO. Contractions to ET-1 and Ang II were determined in the presence and absence of the NADPH oxidase-selective inhibitor gp91ds-tat or the thromboxane-prostanoid receptor antagonist SQ 29,548. Gene expression of endothelin and angiotensin receptors was measured by qPCR. Key findings: Aging reduced ET-1-induced contractions and diminished ETA but increased ETB receptor gene expression levels. Gp91ds-tat inhibited contractions to ET-1 in young and to a greater extent in old animals, whereas SQ 29,548 had no effect. Ang II-induced contractions were weak compared to ET-1 and unaffected by aging, gp91ds-tat, and SQ 29,548. Aging had also no effect on AT(1A) and AT(1B) receptor gene expression levels. Significance: Aging in carotid arteries decreases ETA receptor gene expression and responsiveness to ET-1, which nevertheless becomes increasingly dependent upon NAPDH oxidase activity with age; responses to Ang II and gene expression of its receptors are however unaffected. These findings suggest that physiological aging differentially regulates functional responses to G protein-coupled receptor agonists and the signaling pathways associated with their activation. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecomnsons.org/licenses/by-nc-nd/3.0/).

【 授权许可】

Free