title: Mas receptor overexpression increased Ang-(1-7) relaxation response in renovascular hypertensive rat carotid.
abstract: Renin-angiotensin system (RAS) is an important factor in the pathophysiology of hypertension. Mas receptor, Angiotensin-(1-7) [Ang-(1-7)]-activated receptor, is an important RAS component and exerts protective effects in the vasculature. Ang-(1-7) vascular effects and Mas receptor expression in carotid from renovascular hypertensive (2K-1C) rats is not clear. In the present study we investigated Mas receptor vasodilator response activated by Ang-(1-7) in the carotid rings from sham and 2K-1C rats. Changes in isometric tension were recorded on organ chamber. Mas receptors expression was investigated in carotid by Western blot. Nitric oxide production was evaluated by 2,3-diaminonaphthalene (DAN) and eNOS expression and activity by immunofluoresce and western blot, respectively. Ang-(1-7) induced concentration-dependent vasodilator effect in carotid rings from sham and 2K-1C, which the hypertension increased vasodilatation response. In the 2K-1C carotid rings, A-779 (Mas receptor antagonist) reduced but not abolish the vasodilator effect of Ang-(1-7). Corroborating, Mas receptor protein expression was significantly increased in the 2K-1C rats. L-NAME and ibuprofen decreased Ang-(1-7) vasodilator response and L-NAME plus ibuprofen practically abolish the remaining vasodilatation response. Nitric oxide production is increased due increased of eNOS expression and pSer(1177) activity. Our results demonstrated that renovascular hypertension increased Mas receptors expression and nitric oxide production in the rats carotid which, consequently increased Ang-(1-7)-vasorelaxant response.
authors.affiliation: Department of Pharmacology, Medical School of Ribeirão Preto, Universidade de São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: V C
authors.initials: VC
authors.lastname: Olivon
authors.affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: R D
authors.initials: RD
authors.lastname: Aires
authors.affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: L B
authors.initials: LB
authors.lastname: Santiago
authors.affiliation: Department of Pathology, Medical School of Ribeirão Preto Campus, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: L Z N
authors.initials: LZ
authors.lastname: Ramalho
authors.affiliation: Department of Phamacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: S F
authors.initials: SF
authors.lastname: Cortes
authors.affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: V S
authors.initials: VS
authors.lastname: Lemos
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007052:Ibuprofen / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D010446:Peptide Fragments / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012084:Renin-Angiotensin System; D014664:Vasodilation
chemical_list: D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D009569:Nitric Oxide; D000803:Angiotensin I; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C118790:angiotensin I (1-7); D019331:NG-Nitroarginine Methyl Ester; D007052:Ibuprofen
keywords: Ang-(1– 7); Carotid; Mas receptor; Renovascular hypertension