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.

Role of RAS/Wnt/β-catenin axis activation in the pathogenesis of podocyte injury and tubulo-interstitial nephropathy

“…Alteration of podocyte phenotype causes podocyte dysfunction and albuminuria. Podocytes possess a local RAS that includes AT1 receptor [49,50]. Ang II decreases the ultra-filtration coefficient and increases glomerular capillary perm selectivity thereby causes albuminuria.…”

The Role of β-Adrenergic Overstimulation in the Early Stages of Renal Injury

“…As previously described [23, 24] and summarized here, after the renal function analysis, one kidney was isolated, snap frozen and pulverized in liquid nitrogen, followed by the isolation of RNA using the TRIzol LS Reagent (Life Technologies, Carlsbad, USA). Then, 2 µg total RNA was used to obtain cDNA (High-Capacity cDNA Reverse Transcription Kit; Life Technologies) and real-time PCR was performed using a StepOnePlus (Life Technologies) machine and TaqMan assay system (Life Technologies).…”

Safe Use of Vasopressin and Angiotensin II for Patients with Circulatory Shock

“…In a sheep model of septic shock, angiotensin II did not lead to differences in mesenteric, coronary, and iliac blood flow but decreased renal blood flow. 39 The renal effects of angiotensin II are complex, with its use shown to both improve 39 and worsen 40 renal function in animal models. Angiotensin II preferentially vasoconstricts efferent renal arterioles but not afferent arterioles, which increases renal perfusion pressure and filtration.…”