Renovascular remodeling and renal injury after extended angiotensin II infusion

Author(s)

Malavazzi Casare, Fernando Augusto ^[1] ; Thieme, Karina ^[2] ; Costa-Pessoa, Juliana Martins ^[1] ; Rossoni, Luciana Venturini ^[1] ; Couto, Gisele Kruger ^[1] ; Fernandes, Fernanda Barrinha ^[3] ; Casarini, Dulce Elena ^[3] ; Oliveira-Souza, Maria ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Sch Med, Lab Cellular & Mol Endocrinol, BR-05508900 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Med, Div Nephrol, Sao Paulo - Brazil

• Document type: Journal article
• Source: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY; v. 310, n. 11, p. F1295-F1307, JUN 1 2016.
• Web of Science Citations: 11

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 AT(1) 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 AT(1) receptor. (AU)

• FAPESP's process: 11/14022-0 - Effect of interaction between renin-angiotensin-aldosterone system and endothelin 1 and 3 on renal function
• Grantee: Fernando Augusto Malavazzi Casare
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/23087-4 - Molecular and functional study of membrane transporters
• Grantee: Gerhard Malnic
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 13/19569-3 - Effects of endothelin-3 and leptin in renal morphology and function in vivo: involvement of the intrarenal renin-angiotensin system
• Grantee: Maria Oliveira de Souza
• Support type: Regular Research Grants