期刊
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 310, 期 11, 页码 F1295-F1307出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00471.2015
关键词
angiotensin II; hypertension; renovascular remodeling; inflammation; glomerulosclerosis
资金
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [13/19569-3, 11/14022-0, 13/23087-4]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [302646/2012-4]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [13/23087-4, 13/19569-3, 11/14022-0] Funding Source: FAPESP
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.
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