title: Reduced vasorelaxation to estradiol and G-1 in aged female and adult male rats is associated with GPR30 downregulation.
abstract: Previously, we reported that chronic activation of the estrogen receptor GPR30 by its selective agonist G-1 decreases blood pressure in ovariectomized hypertensive mRen2.Lewis (mRen2) rats but not intact male littermates. Furthermore, G-1 relaxes female mesenteric resistance arteries via both endothelium-dependent and -independent mechanisms. Because of the lack of a blood pressure-lowering effect by G-1 in males and the potential influence of aging on estrogen receptor expression, we hypothesized that GPR30-dependent vasodilation and receptor expression are altered in males and aged females. Thus, we assessed the response to 17β-estradiol or G-1 in mesenteric arteries obtained from 15-wk-old normotensive Lewis and hypertensive mRen2 females and males as well as 52-wk-old Lewis females. Vasodilation to 17β-estradiol (E₂) and G-1 was significantly attenuated in 15-wk-old Lewis and mRen2 males compared with age-matched females. Pretreatment of male vessels with the nitric oxide synthase inhibitor L-NAME had no significant effect on the estradiol or G-1 response. In aged females, E₂ and G-1 vasorelaxation was also significantly blunted; however, L-NAME essentially abolished the response. Associated with the reduced vascular responses, GPR30 expression in mesenteric arteries was approximately 50% lower in males and aged females compared with young females. We conclude that alterations in GPR30 expression and signaling may contribute to vascular dysfunction in aging females and a greater blood pressure in hypertensive males.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA. lindsey@tulane.edu
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Lindsey
authors.forename: Ariel S
authors.initials: AS
authors.lastname: da Silva
authors.forename: Mauro S
authors.initials: MS
authors.lastname: Silva
authors.forename: Mark C
authors.initials: MC
authors.lastname: Chappell
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D003517:Cyclopentanes / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D010052:Ovariectomy; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D055647:Rats, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: C517943:1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone; D003517:Cyclopentanes; C520305:Gper1 protein, rat; D011804:Quinolines; D043562:Receptors, G-Protein-Coupled; C535029:Ren2 protein, rat; D004958:Estradiol; D012083:Renin
keywords: G protein-coupled estrogen receptor; G protein-coupled receptor 30; estradiol-induced vasodilation; menopause