title: Testosterone and β-oestradiol prevent inward remodelling of rat small mesenteric arteries: role of NO and transglutaminase.
abstract: Increasing evidence shows that sex hormones exert a protective effect on the vasculature, especially in the regulation of the active vasomotor responses. However, whether sex hormones affect vascular remodelling is currently unclear. In the present study, we tested the hypothesis that testosterone in males and β-oestradiol in females prevent inward remodelling, possibly through inhibition of cross-linking activity induced by enzymes of the TG (transglutaminase) family. Small mesenteric arteries were isolated from male and female Wistar rats. Dose-dependent relaxation to testosterone and β-oestradiol was inhibited by the NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester), confirming that these hormones induce NO release. When arteries were cannulated, pressurized and kept in organ culture with ET-1 (endothelin-1) for 3 days we observed strong vasoconstriction and inward remodelling. Remodelling was significantly inhibited by testosterone in males, and by β-oestradiol in females. This preventive effect of sex hormones was not observed in the presence of L-NAME. Inward remodelling was also reduced by the inhibitor of TG L682.777, both in males and females. In arteries from female rats, ET-1 increased TG activity, and this effect was prevented by β-oestradiol. L-NAME induced a significant increase in TG activity in the presence of sex hormones in arteries from both genders. We conclude that testosterone and β-oestradiol prevent constriction-induced inward remodelling. Inward remodelling, both in males and females, depends on NO and TG activity. In females, inhibition of inward remodelling could be mediated by NO-mediated inhibition of TG activity.
authors: Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, The Netherlands. lara.delcampo@uam.es
authors: Lara
authors: L
authors: del Campo
authors: Bilge
authors: B
authors: Guvenc Tuna
authors: Mercedes
authors: M
authors: Ferrer
authors: Ed
authors: E
authors: van Bavel
authors: Erik N T P
authors: EN
authors: Bakker
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009213:Myography; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000494:pharmacology*; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D013739:Testosterone; D004958:Estradiol; D019001:Nitric Oxide Synthase; D011503:Transglutaminases; D019331:NG-Nitroarginine Methyl Ester