title: Renovascular remodeling and renal injury after extended angiotensin II infusion.
abstract: Chronic angiotensin II (ANG II) infusion for 1 or 2 wk leads to progressive hypertension and induces inward hypertrophic remodeling in preglomerular vessels, which is associated with increased renal vascular resistance (RVR) and decreased glomerular perfusion. Considering the ability of preglomerular vessels to exhibit adaptive responses, the present study was performed to evaluate glomerular perfusion and renal function after 6 wk of ANG II infusion. To address this study, male Wistar rats were submitted to sham surgery (control) or osmotic minipump insertion (ANG II 200 ng·kg(-1)·min(-1), 42 days). A group of animals was treated or cotreated with losartan (10 mg·kg(-1)·day(-1)), an AT1 receptor antagonist, between days 28 and 42 Chronic ANG II infusion increased systolic blood pressure to 185 ± 4 compared with 108 ± 2 mmHg in control rats. Concomitantly, ANG II-induced hypertension increased intrarenal ANG II level and consequently, preglomerular and glomerular injury. Under this condition, ANG II enhanced the total renal plasma flow (RPF), glomerular filtration rate (GFR), urine flow and induced pressure natriuresis. These changes were accompanied by lower RVR and enlargement of the lumen of interlobular arteries and afferent arterioles, consistent with impairment of renal autoregulatory capability and outward preglomerular remodeling. The glomerular injury culminated with podocyte effacement, albuminuria, tubulointerstitial macrophage infiltration and intrarenal extracellular matrix accumulation. Losartan attenuated most of the effects of ANG II. Our findings provide new information regarding the contribution of ANG II infusion over 2 wk to renal hemodynamics and function via the AT1 receptor.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil;
authors.forename: Fernando Augusto Malavazzi
authors.initials: FA
authors.lastname: Casare
authors.affiliation: Laboratory of Cellular and Molecular Endocrinology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; and.
authors.forename: Karina
authors.initials: K
authors.lastname: Thieme
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil;
authors.forename: Juliana Martins
authors.initials: JM
authors.lastname: Costa-Pessoa
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil;
authors.forename: Luciana Venturini
authors.initials: LV
authors.lastname: Rossoni
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil;
authors.forename: Gisele Kruger
authors.initials: GK
authors.lastname: Couto
authors.affiliation: Division of Nephrology, Department of Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Fernanda Barrinha
authors.initials: FB
authors.lastname: Fernandes
authors.affiliation: Division of Nephrology, Department of Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Dulce Elena
authors.initials: DE
authors.lastname: Casarini
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil; souza@icb.usp.br.
authors.forename: Maria
authors.initials: M
authors.lastname: Oliveira-Souza
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects*; D066253:Vascular Remodeling / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000804:Angiotensin II; D019808:Losartan
keywords: angiotensin II; glomerulosclerosis; hypertension; inflammation; renovascular remodeling