title: Role of estrogens and age in flow-mediated outward remodeling of rat mesenteric resistance arteries.
abstract: In resistance arteries, a chronic increase in blood flow induces hypertrophic outward remodeling. This flow-mediated remodeling (FMR) is absent in male rats aged 10 mo and more. As FMR depends on estrogens in 3-mo-old female rats, we hypothesized that it might be preserved in 12-mo-old female rats. Blood flow was increased in vivo in mesenteric resistance arteries after ligation of the side arteries in 3- and 12-mo-old male and female rats. After 2 wk, high-flow (HF) and normal-flow (NF) arteries were isolated for in vitro analysis. Arterial diameter and cross-sectional area increased in HF arteries compared with NF arteries in 3-mo-old male and female rats. In 12-mo-old rats, diameter increased only in female rats. Endothelial nitric oxide synthase expression and endothelium-mediated relaxation were higher in HF arteries than in NF arteries in all groups. ERK1/2 phosphorylation, NADPH oxidase subunit expression levels, and arterial contractility to KCl and to phenylephrine were greater in HF vessels than in NF vessels in 12-mo-old male rats only. Ovariectomy in 12-mo-old female rats induced a similar pattern with an increased contractility without diameter increase in HF arteries. Treatment of 12-mo-old male rats and ovariectomized female rats with hydralazine, the antioxidant tempol, or the angiotensin II type 1 receptor blocker candesartan restored HF remodeling and normalized arterial contractility in HF vessels. Thus, we found that FMR of resistance arteries remains efficient in 12-mo-old female rats compared with age-matched male rats. A balance between estrogens and vascular contractility might preserve FMR in mature female rats.
authors.forename: K
authors.initials: K
authors.lastname: Tarhouni
authors.forename: M L
authors.initials: ML
authors.lastname: Freidja
authors.forename: A L
authors.initials: AL
authors.lastname: Guihot
authors.forename: E
authors.initials: E
authors.lastname: Vessieres
authors.forename: L
authors.initials: L
authors.lastname: Grimaud
authors.forename: B
authors.initials: B
authors.lastname: Toutain
authors.forename: F
authors.initials: F
authors.lastname: Lenfant
authors.forename: J F
authors.initials: JF
authors.lastname: Arnal
authors.forename: L
authors.initials: L
authors.lastname: Loufrani
authors.forename: D
authors.initials: D
authors.lastname: Henrion
mesh_terms: D000367:Age Factors; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006830:Hydralazine / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels; D013777:Tetrazoles / Q000494:pharmacology; D066253:Vascular Remodeling; D014655:Vascular Resistance; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001562:Benzimidazoles; D001713:Biphenyl Compounds; D003497:Cyclic N-Oxides; D004967:Estrogens; D013113:Spin Labels; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D006830:Hydralazine; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C081643:candesartan; C001803:tempol