Acute and subacute prostaglandin and ANG II inhibition on glomerulotubular dynamics in rats

1990 ◽  
Vol 258 (4) ◽  
pp. F1026-F1035 ◽  
Author(s):  
B. J. Tucker ◽  
R. C. Blantz
Keyword(s):  
Day Treatment ◽  
Control Group ◽  
Ang Ii ◽  
Duration Of Treatment ◽  
Physiological Alterations ◽  
Single Nephron ◽  
Group 2 ◽  
Glomerular Hemodynamics ◽  
Second Period

Prostaglandins (PG) and angiotensin II (ANG II) contribute to regulation of glomerular microcirculation. Acute vs. chronic physiological alterations of glomerular hemodynamics that result from inhibition of either PG or ANG II, or both, and their interaction were examined. Four groups of Munich-Wistar rats were submitted to the following micropuncture studies in euvolemic conditions for measurements of glomerular hemodynamics and tubular fluid reabsorption: 1) an untreated control group, 2) 4- to 6-day inhibition of both PG and angiotensin-converting enzyme activity with meclofenamate and MK-421 (enalapril), 3) 4- to 6-day treatment with enalapril followed by acute PG inhibition in the second measurement period, 4) 4- to 6-day PG inhibition followed by acute enalapril treatment in the second period. Dual 4- to 6-day treatment decreased single-nephron filtration rate (SNGFR, 24 +/- 2 vs. 33 +/- 2 nl/min in control; P less than 0.05) as a result of decreases in single-nephron plasma flow (SNPF) and glomerular hydrostatic pressure gradient (delta P). Treatment with enalapril alone for 4-6 days did not reduce SNGFR and SNPF; however, delta P decreased. Acute addition of meclofenamate did not alter these factors. SNGFR was decreased with 4- to 6-day treatment of meclofenamate from 33 +/- 2 in control to 25 +/- 1 nl/min (P less than 0.05). Acute treatment with enalapril in the 4- to 6-day meclofenamate-treated rats increased SNGFR to values not different from control. The results demonstrated that glomerular hemodynamic alterations consequent to inhibition of ANG II and PG systems differ between chronic and acute treatments. Therefore, interpretation of the role of individual hormonal systems in the control of glomerular hemodynamics should be approached with caution, since effects may be altered by duration of treatment and involvement of other vasoactive systems.

scholarly journals Protective Effect of Boswellic Acids against Doxorubicin-Induced Hepatotoxicity: Impact on Nrf2/HO-1 Defense Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Bassant M. Barakat ◽  
Hebatalla I. Ahmed ◽  
Hoda I. Bahr ◽  
Alaaeldeen M. Elbahaie
Keyword(s):  
Day Treatment ◽  
Protective Role ◽  
Saline Control ◽  
Control Group ◽  
Boswellic Acids ◽  
Stress Markers ◽  
Inhibit Lipid Peroxidation ◽  
Group 2 ◽  
Altered Liver

The current study aimed to investigate the potential protective role of boswellic acids (BAs) against doxorubicin- (DOX-) induced hepatotoxicity. Also, the possible mechanisms underlying this protection; antioxidant, as well as the modulatory effect on the Nrf2 transcription factor/hem oxygenase-1 (Nrf2/HO-1) pathway in liver tissues, was investigated. Animals were allocated to five groups: group 1: the saline control, group 2: the DOX group, animals received DOX (6 mg/kg, i.p.) weekly for a period of three weeks, and groups 3–5: animals received DOX (6 mg/kg, i.p.) weekly and received protective doses of BAs (125, 250, and 500 mg/kg/day). Treatment with BAs significantly improved the altered liver enzyme activities and oxidative stress markers. This was coupled with significant improvement in liver histopathological features. BAs increased the Nrf2 and HO-1 expression, which provided protection against DOX-induced oxidative insult. The present results demonstrated that BAs appear to scavenge ROS and inhibit lipid peroxidation and DNA damage of DOX-induced hepatotoxicity. The antioxidant efficacy of BAs might arise from its modulation of the Nrf2/HO-1 pathway and thereby protected liver from DOX-induced oxidative injury.

Role of angiotensin II in experimental membranous nephropathy

1988 ◽  
Vol 254 (4) ◽  
pp. F500-F506
Author(s):  
F. B. Gabbai ◽  
C. B. Wilson ◽  
R. C. Blantz
Keyword(s):  
Angiotensin Ii ◽  
Hydrostatic Pressure ◽  
Membranous Nephropathy ◽  
Enzyme Inhibitor ◽  
Chronic Administration ◽  
Ang Ii ◽  
Glomerular Injury ◽  
Single Nephron ◽  
Glomerular Hemodynamics

Glomerular hemodynamics measurements in rats with experimental membranous nephropathy [passive Heymann nephritis (PHN)] have demonstrated that the appearance of proteinuria 5 days after administration of anti-Fx1A antibody is temporally related to changes in the glomerular ultrafiltration coefficient (LpA). Previous studies in other models of glomerular injury have suggested a significant role for angiotensin II (ANG II) in the glomerular hemodynamic abnormalities. To evaluate the possible role of ANG II in the LpA decrease, converting enzyme inhibitor (CEI) was administered acutely or chronically (5 days before and after induction of PHN) to rats with PHN. Acute ANG II blockade produced a fall in mean arterial pressure (MAP), single-nephron glomerular filtration rate (SNGFR), absolute proximal reabsorption (APR), single-nephron plasma flow, single-nephron blood flow, and glomerular capillary hydrostatic pressure (PG); however, no changes in LpA were detected. Chronic administration of CEI (MK421, 5 mg.kg-1.day-1) in the drinking water was associated with a fall in MAP; however, both SNGFR and APR increased. PG and the transcapillary hydrostatic pressure gradient were unchanged, and LpA remained depressed. These results suggest that reduction of LpA in rats with PHN is ANG II independent and that other mechanisms are required to explain these changes in glomerular hemodynamics.

Effects of erdosteine on cyclosporin-A-induced nephrotoxicity

2011 ◽  
Vol 31 (6) ◽  
pp. 565-573 ◽  
Author(s):  
M Tutanc ◽  
V Arica ◽  
N Yılmaz ◽  
A Nacar ◽  
I Zararsiz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cyclosporin A ◽  
Protective Role ◽  
Control Group ◽  
Albino Rats ◽  
Protective Mechanism ◽  
Antioxidant Parameters ◽  
Group 2 ◽  
Wistar Albino Rats

Aim: In cyclosporin-A (CsA)-induced toxicity, oxidative stress has been implicated as a potential responsible mechanism. Therefore, we aimed to investigate the protective role of erdosteine against CsA-induced nephrotoxicity in terms of tissue oxidant/antioxidant parameters and light microscopy in rats. Materials and methods: Wistar albino rats were randomly separated into four groups. Group 1 rats treated with sodium chloride served as the control, group 2 rats were treated with CsA, group 3 with CsA plus erdosteine, and group 4 with erdosteine alone. Animals were killed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (Cr), uric acid (UA), total protein (TP), and albumin (ALB) levels. Kidney sections were analyzed for malondialdehyde (MDA) and nitric oxide (NO) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, as well as for histopathological changes. Results: In the CsA group, MDA, GSH-Px, BUN, and Cr levels were increased. The TP and ALB levels were decreased. These changes had been improved by erdosteine administration. Other biochemical parameters did not show any significant change. Conclusion: These results indicate that erdosteine produces a protective mechanism against CsA-induced nephrotoxicity and suggest a role of oxidative stress in pathogenesis.

Splanchnic blood flow and hepatic glucose production in exercising humans: role of renin-angiotensin system

2001 ◽  
Vol 281 (6) ◽  
pp. R1854-R1861 ◽  
Author(s):  
Raynald Bergeron ◽  
Michael Kjær ◽  
Lene Simonsen ◽  
Jens Bülow ◽  
Dorthe Skovgaard ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renin Angiotensin System ◽  
Glucose Production ◽  
Splanchnic Blood Flow ◽  
Control Group ◽  
Moderate Exercise ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin

The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O2 consumption (V˙o 2 max) followed by 30 min at 70% V˙o 2 maxeither with [angiotensin-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an ∼20-fold increase ( P < 0.001) in ANG II levels in the control group (5.4 ± 1.0 to 102.0 ± 25.1 pg/ml), whereas this response was blunted during ACE blockade (8.1 ± 1.2 to 13.2 ± 2.4 pg/ml) and in response to an orthostatic challenge performed postexercise. Apart from lactate and cortisol, which were higher in the ACE-blockade group vs. the control group, hormones, metabolites, V˙o 2, and RER followed the same pattern of changes in ACE-blockade and control groups during exercise. Splanchnic blood flow (at rest: 1.67 ± 0.12, ACE blockade; 1.59 ± 0.18 l/min, control) decreased during moderate exercise (0.78 ± 0.07, ACE blockade; 0.74 ± 0.14 l/min, control), whereas splanchnic glucose production (at rest: 0.50 ± 0.06, ACE blockade; 0.68 ± 0.10 mmol/min, control) increased during moderate exercise (1.97 ± 0.29, ACE blockade; 1.91 ± 0.41 mmol/min, control). Refuting a major role of the RAS for these responses, no differences in the pattern of change of splanchnic blood flow and splanchnic glucose production were observed during ACE blockade compared with controls. This study demonstrates that the normal increase in ANG II levels observed during prolonged exercise in humans does not play a major role in the regulation of splanchnic blood flow and glucose production.

scholarly journals Renal Cortical Vasoconstriction Contributes to Development of Salt-Sensitive Hypertension after Angiotensin II Exposure

2001 ◽  
Vol 12 (11) ◽  
pp. 2263-2271
Author(s):  
MARTHA FRANCO ◽  
EDILIA TAPIA ◽  
JOSÉ SANTAMARÍA ◽  
IGNACIO ZAFRA ◽  
ROMEO GARCÍA-TORRES ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Plasma Flow ◽  
Critical Role ◽  
Progressive Increase ◽  
Tubulointerstitial Injury ◽  
High Salt Diet ◽  
Single Nephron ◽  
Glomerular Hemodynamics ◽  
Salt Sensitive Hypertension

Abstract. Rats that are administered angiotensin II (AngII) for 2 wk develop persistent salt-sensitive hypertension, which can be prevented by the immunosuppressor mycophenolate mofetil (MMF) given during the AngII infusion. This study examined the contribution of glomerular hemodynamics (GFR dynamics) in the post-AngII hypertensive response to a high-salt diet (HSD) and the effect of MMF treatment. During AngII administration, rats developed severe hypertension (systolic BP [SBP], 185 ± 3.9 mmHg), proteinuria, afferent and efferent vasoconstriction, and glomerular hypertension. Rats that received AngII+MMF showed similar responses to AngII; however, they developed lower proteinuria (P < 0.05). At 2 wk, AngII was withdrawn and SBP returned toward normal. Rats were then placed on an HSD (4% NaCl), resulting in a progressive increase in SBP (155 ± 8.2 mmHg at week 1 and 163 ± 4.5 mmHg at week 5). GFR dynamic alterations persisted after AngII was stopped, i.e., afferent and efferent vasoconstriction, decreased glomerular plasma flow and single-nephron GFR, and lower ultrafiltration coefficient. These changes correlated with the thickening of the afferent arteriole and with focal tubulointerstitial injury. In the AngII+MMF group, SBP remained unchanged throughout the HSD period (146 ± 2.3 mmHg at week 1 and 148 ± 4.4 mmHg at week 5) in association with less afferent arteriolar thickening and tubulointerstitial injury. Single-nephron GFR, glomerular plasma flow, efferent resistance, and ultrafiltration coefficient returned to normal with a significant reduction in afferent resistance. These results suggest a critical role of cortical vasoconstriction in salt-sensitive hypertension. The MMF-induced prevention of these changes suggests that immune mechanisms are involved in the vasoconstrictive response.

scholarly journals NADPH Oxidase 4 Signaling in a Ventilator-induced Lung Injury Mouse Model

2021 ◽  
Author(s):  
Sang Hoon Lee ◽  
Mi Hwa Shin ◽  
Ah Young Leem ◽  
Su Hwan Lee ◽  
Kyung Soo Chung ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lavage Fluid ◽  
Lung Damage ◽  
Control Group ◽  
Group 4 ◽  
Ventilator Induced Lung Injury ◽  
Cell Counts ◽  
Group 5 ◽  
Group 2

Abstract For patients with acute respiratory distress syndrome, a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. We investigated the role of NOX4 in a ventilator-induced lung injury (VILI) model.Wild-type (WT) male C57BL/6J mice and NOX4 knockout (KO) male mice were divided into five groups: (1) control group; (2) high tidal ventilation (HTV) group: WT mice + HTV; (3) NOX4 KO group; (4) NOX4 KO with HTV group; (5) NOX4 inhibitor group: WT mice + HTV + NOX4 inhibitor. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined.In the NOX4 inhibitor group, cell counts and protein concentrations from BALF were significantly lower than those in the HTV group (both, p<0.001). In the NOX4 KO group and the NOX4 inhibitor group, EphA2 levels were significantly lower than those in the HTV group (p<0.001). NOX4 levels were significantly higher in patients with pneumonia and patients who received ventilator treatment in the ICU.In the VILI model, it may be possible to block VILI using NOX4 antibodies.

scholarly journals The Role of Rice Hull Liquid Smoke in the Traumatic Ulcer Healing

2020 ◽  
Author(s):  
Ira Arundina ◽  
Indeswati Diyatri ◽  
Tuti Kusumaningsih ◽  
Meircurius Dwi Condro Surboyo ◽  
Elita Monica ◽  
...  
Keyword(s):  
Ulcer Healing ◽  
Transforming Growth Factor ◽  
Day Treatment ◽  
Transforming Growth Factor Β ◽  
Wistar Rat ◽  
Rice Hull ◽  
Control Group ◽  
Liquid Smoke ◽  
Hematoxylin And Eosin

Abstract Objective The aim of this study was to prove the role of rice hull liquid smoke (RH-LS) on lymphocytes, macrophages, fibroblasts, interleukin 6 (IL-6), and transforming growth factor β (TGF-β) expression during traumatic ulcer healing. Materials and Methods The RH-LS was obtained from the pyrolysis process. Traumatic ulcers were made 10 mm along the labial fornix incisive inferior of Wistar rat using a round stainless-steel blade. In control group, traumatic ulcers were treated using sterile water, and meanwhile in experimental group were treated using RH-LS once a day for 3, 5, and 7 days. After treatment, animal was terminated and their labial fornix incisive inferior tissues were biopsy and stained using hematoxylin and eosin staining to determine lymphocytes, macrophages, and fibroblasts. The IL-6 and TGF-β expressions were analyzed used immunohistochemistry staining. Result The lymphocytes, macrophages, and fibroblasts were higher in the RH-LS group for 3-, 5-, and 7-day treatment (p < 0.05). The IL-6 expression was higher only in the 5-day treatment, and the TGF-β expression was higher in the 3- and 7-day treatment. Conclusion The RH-LS able to accelerated the traumatic ulcer healing by increasing the number of lymphocytes, macrophages, fibroblasts, IL-6, and TGF-β expression.

The effect of transcutaneous electrical nerve stimulation on the viability of random skin flaps in rats

2002 ◽  
Vol 10 (4) ◽  
pp. 151-154 ◽  
Author(s):  
Richard Eloin Liebano ◽  
Lydia Masako Ferreira ◽  
Miguel Sabino Neto
Keyword(s):  
Nerve Stimulation ◽  
Transcutaneous Electrical Nerve Stimulation ◽  
Skin Flap ◽  
Control Group ◽  
Skin Flaps ◽  
Electrical Nerve Stimulation ◽  
Flap Viability ◽  
Group 2 ◽  
Group 1

The aim of this study was to determine the role of transcutaneous electrical nerve stimulation (TENS) in the viability of random skin flaps. In 30 Wistar-EPM rats, a random 10×4 cm skin flap was raised and a plastic barrier was interposed between the flap and its bed. Immediately after surgery and for two subsequent days, the rats in group 1 (the control group) were anesthetized for 1 h with the electrodes positioned in the base of the flap and without the administration of the electric stimulus. The rats in group 2 (the treatment group) were submitted to TENS for 1 h immediately after the surgery and for two subsequent days. The percentage of necrotic area (averages of 43.11% in the rats in group 1 and 23.52% in the rats in group 2) was calculated on the seventh postoperative day in both groups. Statistical analysis proved that TENS was more efficient in increasing random skin flap viability than was the method used in the control group.

scholarly journals Unexpected effect of angiotensin AT1 receptor blockade on tubuloglomerular feedback in early subtotal nephrectomy

2009 ◽  
Vol 296 (5) ◽  
pp. F1158-F1165 ◽  
Author(s):  
Prabhleen Singh ◽  
Aihua Deng ◽  
Roland C. Blantz ◽  
Scott C. Thomson
Keyword(s):  
Tubuloglomerular Feedback ◽  
Male Rats ◽  
Ang Ii ◽  
Subtotal Nephrectomy ◽  
Henle's Loop ◽  
Salutary Effect ◽  
Single Nephron ◽  
Distal Delivery

After subtotal nephrectomy (STN), the remaining nephrons engage in hyperfiltration, which may be facilitated by a reduced sensitivity of the tubuloglomerular feedback (TGF) response to increased distal delivery. However, a muted TGF response would contradict the notion of remnant kidney as a prototype of angiotensin II (ANG II) excess, since ANG II normally sensitizes the TGF response and stimulates proximal reabsorption. We examined the role of ANG II as a modulator of TGF and proximal reabsorption in 7 days after STN in male rats. Single-nephron glomerular filtration rate (SNGFR) and proximal reabsorption ( Jprox) were measured in late proximal collections while perfusing Henle's loop for minimal and maximal TGF stimulation in rats treated with the angiotensin type 1 (AT1) receptor blocker losartan or placebo in drinking water for 7 days. Perfusion of Henle's loop yielded a robust TGF response in sham-operated rats. In STN, the feedback responses were highly variable and nil, on average. Paradoxical TGF responses to augmented late proximal flow were confirmed in SNGFR measurements from the early distal nephron. Chronic losartan treatment normalized the average TGF response without reducing the variability. Jprox was subtly affected by chronic losartan in sham surgery or STN, after controlling for differences in SNGFR. However, when administered acutely into the early S1 segment, losartan potently suppressed Jprox in STN and sham-operated rats alike. Chronic losartan stabilizes the TGF system in remnant kidneys. This cannot be explained by currently known actions of AT1 receptors but is commensurate with a salutary effect of an intact TGF system on dynamic autoregulation of intraglomerular flow and pressure.

HEPARIN-RELEASED PLATELET FACTOR 4 (HR-PF4) IN DIABETIC MICR0VAS-CULAR DISEASE

1987 ◽  
Author(s):  
C Boschetti ◽  
A Vicari ◽  
E Cofrancesco ◽  
A Della Volpe ◽  
G Moreo ◽  
...  
Keyword(s):  
Protein C ◽  
Microvascular Disease ◽  
Macrovascular Disease ◽  
Control Group ◽  
Diabetic Patients ◽  
Platelet Factor ◽  
Tissue Plasminogen ◽  
Insulin Dependent ◽  
Group 2

When heparin is injected i.v. as a bolus, PF4 but not (β-throm boglobulin ((βTG) is released immediately. HR-PF4 is not liberated from platelets but from the endothelial cells of vessels which serve as storage sites. The role of platelet activation in diabetic microvascular disease is still controversial, however there is experimental evidence of vascular injury and hemostatic activation preceding the appearance of microvascular disease. The contradictory results so far obtained in man may be partly attributed to the heterogeneity of the diabetic patients studied. We studied 20 insulin-dependent diabetics (age 21-40) in stable metabolic equilibrium (mean HbAlc=7.6%). 10 without fluoroangiographic evidence of retinopathy (Group l) and 10 with retinopathy (Group 2). None had signs or symptoms of macrovascular disease. The control group consisted of 10 healthy volunteers (age 22-39). No medication except insulin was taken for at least 10 days preceding the study. 12 h before the study all subjects received aspirin 500 mg p.o. Plasma (βTG and PF4 were determined before (basal) and 5,30,90 min after a heparin bolus i.v. (5000 U). Protein C, factor VIIIR:Ag and tissue plasminogen activator were also measured in plasma.

Sign in / Sign up

Export Citation Format

Share Document