scholarly journals The Effect of Endogenous Angiotensin II on Alveolar Fluid Clearance in Rats with Acute Lung Injury

2012 ◽  
Vol 19 (5) ◽  
pp. 311-318 ◽  
Author(s):  
Jia Deng ◽  
Dao-xin Wang ◽  
Wang Deng ◽  
Chang-yi Li ◽  
Jin Tong
Keyword(s):  
Acute Lung Injury ◽  
Angiotensin Ii ◽  
Lung Injury ◽  
Messenger Rna ◽  
Time Course ◽  
Vital Role ◽  
Ang Ii ◽  
Alveolar Fluid Clearance ◽  
Sprague Dawley ◽  
Edema Formation

BACKGROUND: In acute lung injury (ALI), angiotensin II (Ang II) plays a vital role in the stimulation of pulmonary permeability edema formation through the angiotensin type 1 (AT1) receptor. The effect of Ang II on alveolar fluid clearance (AFC) in ALI remains unknown.METHODS: Sprague Dawley rats were anesthetized and intratracheally injected with 1 mg/kg lipopolysaccharide (LPS), while control rats received saline. The AT1receptor antagonist ZD7155 was injected intraperitoneally (10 mg/kg) 30 min before LPS administration. The lungs were isolated for AFC measurement, and alpha-epithelial sodium channel (ENaC) messenger RNA and protein expression were detected by reverse-transcription polymerase chain reaction and Western blot.RESULTS: LPS-induced ALI caused an increase in Ang II levels in plasma and lung tissue but a decrease in AFC. The time course of Ang II levels paralleled that of AFC. Pretreatment with ZD7155 prevented ALI-induced reduction of AFC. ZD7155 also reversed the ALI-induced reduction of beta-ENaC and gamma-ENaC levels, and further decreased alpha-ENaC levels.CONCLUSIONS: These findings suggest that endogenous Ang II inhibits AFC and dysregulates ENaC expression via AT1receptors, which contribute to alveolar filling and pulmonary edema in LPS-induced ALI.

Angiotensin II and the fibroproliferative response to acute lung injury

2004 ◽  
Vol 286 (1) ◽  
pp. L156-L164 ◽  
Author(s):  
Richard P. Marshall ◽  
Peter Gohlke ◽  
Rachel C. Chambers ◽  
David C. Howell ◽  
Steve E. Bottoms ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Angiotensin Ii ◽  
Lung Injury ◽  
Ace Inhibitors ◽  
Transforming Growth Factor ◽  
Lung Fibroblasts ◽  
Collagen Deposition ◽  
Ang Ii ◽  
Potent Inducer

Angiotensin II (ANG II), generated by activation of local renin-angiotensin systems, is believed to play an important role in tissue repair and remodeling, in part via transforming growth factor-β (TGF-β). Angiotensin-converting enzyme (ACE) inhibitors have been shown to abrogate experimental lung injury via a number of potential mechanisms; however, the potentially fibroproliferative role for ANG II in the lung has not been characterized. We hypothesized that, after lung injury, ANG II would stimulate fibroblast procollagen synthesis and promote lung collagen deposition in rats. In vitro, ANG II was a potent inducer of procollagen production in human lung fibroblasts via activation of the type 1 receptor and, at least in part, via the autocrine action of TGF-β. After bleomycin-induced lung injury, an increase in lung ANG II concentration was observed by day 3 that preceded increases in lung collagen and was maintained until death at day 21. Administration of an ACE inhibitor (ramipril) reduced ACE activity, ANG II concentration, TGF-β expression, and collagen deposition. Losartan (an ANG II type 1 receptor antagonist) also attenuated the increase in TGF-β expression and lung collagen deposition. These observations suggest that ANG II, possibly generated locally within the lung, may play an important role in the fibrotic response to acute lung injury, at least in part via the action of TGF-β. ACE inhibitors and receptor antagonists, already widely used clinically, should be assessed as potential new therapies for fibrotic lung disease.

scholarly journals Angiotensin II stimulates trafficking of NHE3, NaPi2, and associated proteins into the proximal tubule microvilli

2010 ◽  
Vol 298 (1) ◽  
pp. F177-F186 ◽  
Author(s):  
Anne D. M. Riquier-Brison ◽  
Patrick K. K. Leong ◽  
Kaarina Pihakaski-Maunsbach ◽  
Alicia A. McDonough
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Flow Rate ◽  
Enzyme Inhibitor ◽  
Volume Flow Rate ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Water Reabsorption ◽  
Associated Proteins ◽  
Gradient Fractionation

Angiotensin II (ANG II) stimulates proximal tubule (PT) sodium and water reabsorption. We showed that treating rats acutely with the angiotensin-converting enzyme inhibitor captopril decreases PT salt and water reabsorption and provokes rapid redistribution of the Na+/H+ exchanger isoform 3 (NHE3), Na+/Pi cotransporter 2 (NaPi2), and associated proteins out of the microvilli. The aim of the present study was to determine whether acute ANG II infusion increases the abundance of PT NHE3, NaPi2, and associated proteins in the microvilli available for reabsorbing NaCl. Male Sprague-Dawley rats were infused with a dose of captopril (12 μg/min for 20 min) that increased PT flow rate ∼20% with no change in blood pressure (BP) or glomerular filtration rate (GFR). When ANG II (20 ng·kg−1·min−1 for 20 min) was added to the captopril infusate, PT volume flow rate returned to baseline without changing BP or GFR. After captopril, NHE3 was localized to the base of the microvilli and NaPi2 to subapical cytoplasmic vesicles; after 20 min ANG II, both NHE3 and NaPi2 redistributed into the microvilli, assayed by confocal microscopy and density gradient fractionation. Additional PT proteins that redistributed into low-density microvilli-enriched membranes in response to ANG II included myosin VI, DPPIV, NHERF-1, ezrin, megalin, vacuolar H+-ATPase, aminopeptidase N, and clathrin. In summary, in response to 20 min ANG II in the absence of a change in BP or GFR, multiple proteins traffic into the PT brush-border microvilli where they likely contribute to the rapid increase in PT salt and water reabsorption.

scholarly journals Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury

2018 ◽  
Vol Volume 11 ◽  
pp. 169-178 ◽  
Author(s):  
Mario Menk ◽  
Jan Adriaan Graw ◽  
Clarissa von Haefen ◽  
Henrik Kurt Alexander Steinkraus ◽  
Burkhard Lachmann ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Angiotensin Ii ◽  
Lung Injury ◽  
Receptor Agonist ◽  
Pulmonary Inflammation ◽  
Compound 21

Angiotensin II regulates nephrogenesis and renal vascular development

1995 ◽  
Vol 269 (1) ◽  
pp. F110-F115 ◽  
Author(s):  
A. Tufro-McReddie ◽  
L. M. Romano ◽  
J. M. Harris ◽  
L. Ferder ◽  
R. A. Gomez
Keyword(s):  
Angiotensin Ii ◽  
Kidney Development ◽  
Rana Catesbeiana ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Ang Ii ◽  
Newborn Rats ◽  
Sprague Dawley ◽  
Renal Growth ◽  
Glomerular Size ◽  
Renal Vascular

To test the hypothesis that angiotensin II (ANG II) is necessary for normal embryonic and postnatal kidney development, the effect of angiotensin receptor blockade or angiotensin converting enzyme inhibition on nephrovascular development was studied in newborn Sprague-Dawley rats and in Rana catesbeiana tadpoles undergoing prometamorphosis. Blockade of ANG II type 1 receptor (AT1) in newborn rats induced an arrest in nephrovascular maturation and renal growth, resulting in altered kidney architecture, characterized by fewer, thicker, and shorter afferent arterioles, reduced glomerular size and number, and tubular dilatation. Inhibition of ANG II generation in tadpoles induced even more marked developmental renal abnormalities. Blockade of ANG II type 2 receptor (AT2) in newborn rats did not alter renal growth or morphology. Results indicate that ANG II regulates nephrovascular development, a role that is conserved across species.

Keratinocyte growth factor therapy in murine oleic acid-induced acute lung injury

2005 ◽  
Vol 288 (6) ◽  
pp. L1179-L1192 ◽  
Author(s):  
K. Ulrich ◽  
M. Stern ◽  
M. E. Goddard ◽  
J. Williams ◽  
J. Zhu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acute Lung Injury ◽  
Gene Delivery ◽  
Lung Injury ◽  
Time Course ◽  
Lung Compliance ◽  
Alveolar Type ◽  
Protein Therapy ◽  
Cell Numbers ◽  
Atii Cell

Alveolar type II (ATII) cell proliferation and differentiation are important mechanisms in repair following injury to the alveolar epithelium. KGF is a potent ATII cell mitogen, which has been demonstrated to be protective in a number of animal models of lung injury. We have assessed the effect of recombinant human KGF (rhKGF) and liposome-mediated KGF gene delivery in vivo and evaluated the potential of KGF as a therapy for acute lung injury in mice. rhKGF was administered intratracheally in male BALB/c mice to assess dose response and time course of proliferation. SP-B immunohistochemistry demonstrated significant increases in ATII cell numbers at all rhKGF doses compared with control animals and peaked 2 days following administration of 10 mg/kg rhKGF. Protein therapy in general is very expensive, and gene therapy has been suggested as a cheaper alternative for many protein replacement therapies. We evaluated the effect of topical and systemic liposome-mediated KGF-gene delivery on ATII cell proliferation. SP-B immunohistochemistry showed only modest increases in ATII cell numbers following gene delivery, and these approaches were therefore not believed to be capable of reaching therapeutic levels. The effect of rhKGF was evaluated in a murine model of OA-induced lung injury. This model was found to be associated with significant alveolar damage leading to severe impairment of gas exchange and lung compliance. Pretreatment with rhKGF 2 days before intravenous OA challenge resulted in significant improvements in Po2, Pco2, and lung compliance. This study suggests the feasibility of KGF as a therapy for acute lung injury.

scholarly journals Time Course Change of Phagocytes and Proinflammatory activities in BALF in Endotoxin-induced Acute Lung Injury

1997 ◽  
Vol 44 (2) ◽  
pp. 360
Author(s):  
Seung Hyug Moon ◽  
Je Ho Oh ◽  
Sung Woo Park ◽  
Eun Kyung Namgung ◽  
Shin Young Ki ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Time Course

Embryonic lethality in Dear gene-deficient mice: new player in angiogenesis

2005 ◽  
Vol 23 (3) ◽  
pp. 257-268 ◽  
Author(s):  
Victoria L. M. Herrera ◽  
Lorenz R. B. Ponce ◽  
Pia D. Bagamasbad ◽  
Benjamin D. VanPelt ◽  
Tamara Didishvili ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Embryonic Lethality ◽  
Female Rats ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Angiotensin Ii Receptor ◽  
Endothelin 1 ◽  
Receptor Isoforms ◽  
Age Range ◽  
Deficient Mice

The dual endothelin-1/angiotensin II receptor (Dear) binds endothelin-1 (ET-1) and angiotensin II (ANG II) with equal affinities in the Dahl S/JRHS rat strain. To elucidate its physiological significance within the context of multiple receptor isoforms and diverse ET-1 and ANG II functions spanning blood pressure regulation, tumor proliferation, and angiogenesis, we characterized mouse Dear and Dear-deficient mice. Unlike null mutant models of ET-1, ANG II, and all other ET-1 and ANG II receptors, Dear−/− deficiency results in impaired angiogenesis, dysregulated neuroepithelial development, and embryonic lethality by embryonic day 12.5. Interestingly, mouse Dear does not bind ANG II, similar to Dahl R/JRHS rat Dear, but binds ET-1 and vascular endothelial growth factor (VEGF) signal peptide (VEGFsp) with equal affinities, suggesting a putative novel multifunction for VEGFsp and a parsimonious mechanism for coordination of VEGF-induced and Dear-mediated pathways. Consistent with its developmental angiogenic role, Dear inhibition results in decreased tumor growth in B16-F10 melanoma cell-induced subcutaneous tumor in female Dear+/−/C57BL6BC10 mice, but not in males (age 3.5 mo), and in 127Cs radiation-induced orthotopic mammary tumors in Sprague-Dawley female rats (age range 3–6.5 mo). Altogether, the data identify Dear as a new player in angiogenesis during development downstream to, and nonredundant with, VEGF-mediated pathways, as well as a putative modulator of tumor angiogenesis acting within a gender-specific paradigm.

Abstract 41: Fructose Stimulates Na/H Exchanger 3 Activity and Enhances the Ability of Angiotensin II to Activate Na/H Exchanger 3 in the Proximal Tubule

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Pablo Cabral ◽  
Nancy Hong ◽  
Jeffrey Garvin
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Physiological Saline ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Basal Rate ◽  
Low Concentrations ◽  
Sprague Dawley Rats ◽  
High Fructose ◽  
Salt Sensitive Hypertension

Consumption of high-fructose corn syrup as a sweetener has increased dramatically. Fructose has been implicated in the epidemic of diabetes, obesity and hypertension including salt-sensitive hypertension. However, the mechanisms are poorly understood. The proximal nephron reabsorbs 60-70% of the fluid and Na, and most of the filtered bicarbonate via Na/H exchanger 3. Enhanced proximal nephron transport has been implicated in several forms of hypertension. We hypothesized that fructose stimulates NHE3 activity and enhances the ability of angiotensin II (ANG II) to activate NHE3 in the proximal tubule. To test our hypothesis we isolated and perfused proximal tubules from Sprague Dawley rats. NHE3 activity was measured as the recovery of intracellular pH after an NH4Cl acid pulse using the pH sensitive dye BCECF. The rate of pH recovery was measured in Fluorescent Units per second (FU/sec). In the presence of a 5.5 mM glucose-containing physiological saline the basal rate of pH recovery was 3.1 ± 0.8 FU/sec. When the luminal solution was exchanged to a 0.6 mM glucose + 5 mM fructose-containing physiological saline in a second period, the rate of pH recovery increased to 5 ± 1 FU/sec (p<0.03, n=8).To study whether this effect was due to the addition of fructose or the removal of glucose to the lumen, we performed a separate set of experiments where 5 mM glucose was substituted for 5 mM fructose. In the presence of 0.6 mM glucose the basal rate of pH recovery was 3.6 ± 1.5 FU/sec. When 5 mM fructose was added the rate of pH recovery increased to 5.9 ± 2 FU/sec (p<0.02, n=5). Control experiments showed no differences between periods when 5 mm glucose was added back to the luminal perfusate. Finally, we tested the effect of low concentrations of ANG II in the presence or absence of luminal fructose. In the presence of 5.5 mM glucose, ANG II 10-12 M did not affect the rate of pH recovery (change: -1.1 ± 0.5 FU/sec, n=9). However, in the presence of 5 mM fructose, ANG II increased the rate of pH recovery (change: 4.0 ± 2.2 FU/sec, p< 0.03 n=6). We conclude that acute treatment with fructose stimulates NHE3 activity and enhances the ability of ANG II to activate NHE3 in the proximal tubule. These results may partially explain the mechanism by which a fructose diet induces hypertension.

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