scholarly journals Angiotensin II Binding to Renomedullary Interstitial Cells Is Regulated by Osmolality

2001 ◽  
Vol 12 (3) ◽  
pp. 450-455
Author(s):  
CHRISTINE MARIC ◽  
DAVID CASLEY ◽  
PETER J. HARRIS ◽  
DAINE ALCORN
Keyword(s):  
Angiotensin Ii ◽  
Peptide Binding ◽  
Interstitial Cells ◽  
Ang Ii ◽  
Outer Medulla ◽  
Receptor Ligand ◽  
The Media ◽  
Hoe 140 ◽  
Induced Changes ◽  
Renal Medullary Function

Abstract. Angiotensin II (Ang II) AT1A receptors are localized to renomedullary interstitial cells (RMIC) in the inner stripe of the outer medulla but not in the inner medulla. Thus, there seems to be a correlation between decreases in AT1A receptor binding to RMIC and increases in interstitial osmolality, suggesting that osmolality is important in determining Ang II binding to RMIC. Cultured RMIC were incubated in media of differing osmolalities (330, 630, 930, and 1230 mOsm/kgH2O). 125I-[Sar1, Ile8] Ang II binding to AT1A receptors on RMIC grown in hyperosmolal media (930 mOsm/kgH2O) was reduced compared with isoosmolal (330 mOsm/kgH2O) media and was progressively reduced with further increases of osmolality. Similar studies were performed using bradykinin (BK) as a control peptide. Binding of the BK receptor ligand 125I-[HPP-Hoe 140] to B2 receptors was not affected by varying osmolality of the media. Reverse transcriptase-PCR demonstrated the presence of the mRNA expression for both AT1A and B2 receptors at each osmolality. The conclusion is that osmolality modulates Ang II binding to RMIC; in these cells, this phenomenon is restricted to Ang II as BK binding is not affected. Osmolality-induced changes in Ang II binding may modulate the actions of this peptide on RMIC and provide an important mechanism by which these cells modulate renal medullary function.

scholarly journals Angiotensin II stimulates superoxide production in the thick ascending limb by activating NOX4

2012 ◽  
Vol 303 (7) ◽  
pp. C781-C789 ◽  
Author(s):  
Katherine J. Massey ◽  
Nancy J. Hong ◽  
Jeffrey L. Garvin
Keyword(s):  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Knockout Mice ◽  
Thick Ascending Limb ◽  
Ang Ii ◽  
Wild Type ◽  
Outer Medulla ◽  
Catalytic Subunits ◽  
In The Wild

Angiotensin II (ANG II) stimulates production of superoxide (O2−) by NADPH oxidase (NOX) in medullary thick ascending limbs (TALs). There are three isoforms of the catalytic subunit (NOX1, 2, and 4) known to be expressed in the kidney. We hypothesized that NOX2 mediates ANG II-induced O2− production by TALs. To test this, we measured NOX1, 2, and 4 mRNA and protein by RT-PCR and Western blot in TAL suspensions from rats and found three catalytic subunits expressed in the TAL. We measured O2− production using a lucigenin-based assay. To assess the contribution of NOX2, we measured ANG II-induced O2− production in wild-type and NOX2 knockout mice (KO). ANG II increased O2− production by 346 relative light units (RLU)/mg protein in the wild-type mice ( n = 9; P < 0.0007 vs. control). In the knockout mice, ANG II increased O2− production by 290 RLU/mg protein ( n = 9; P < 0.007 vs. control). This suggests that NOX2 does not contribute to ANG II-induced O2− production ( P < 0.6 WT vs. KO). To test whether NOX4 mediates the effect of ANG II, we selectively decreased NOX4 expression in rats using an adenovirus that expresses NOX4 short hairpin (sh)RNA. Six to seven days after in vivo transduction of the kidney outer medulla, NOX4 mRNA was reduced by 77%, while NOX1 and NOX2 mRNA was unaffected. In control TALs, ANG II stimulated O2− production by 96%. In TALs transduced with NOX4 shRNA, ANG II-stimulated O2− production was not significantly different from the baseline. We concluded that NOX4 is the main catalytic isoform of NADPH oxidase that contributes to ANG II-stimulated O2− production by TALs.

Cyclic Pressure and Angiotensin II Influence the Biomechanical Properties of Aortic Valves

2013 ◽  
Vol 136 (1) ◽  
Author(s):  
Valtresa Myles ◽  
Jun Liao ◽  
James N. Warnock
Keyword(s):  
Angiotensin Ii ◽  
Aortic Valve ◽  
Biomechanical Properties ◽  
Interstitial Cells ◽  
Collagen Content ◽  
Cell Stiffness ◽  
Ang Ii ◽  
Aortic Valves ◽  
Cyclic Pressure ◽  
Aortic Valve Leaflets

Hypertension is a known risk factor for aortic stenosis. The elevated blood pressure increases the transvalvular load and can elicit inflammation and extracellular matrix (ECM) remodeling. Elevated cyclic pressure and the vasoactive agent angiotensin II (Ang II) both promote collagen synthesis, an early hallmark of aortic sclerosis. In the current study, it was hypothesized that elevated cyclic pressure and/or angiotensin II decreases extensibility of aortic valve leaflets due to an increase in collagen content and/or interstitial cell stiffness. Porcine aortic valve leaflets were exposed to pressure conditions of increasing magnitude (static atmospheric pressure, 80, and 120 mmHg) with and without 10−6 M Ang II. Biaxial mechanical testing was performed to determine extensibility in the circumferential and radial directions and collagen content was determined using a quantitative dye-binding method at 24 and 48 h. Isolated aortic valve interstitial cells exposed to the same experimental conditions were subjected to atomic force microscopy to assess cellular stiffness at 24 h. Leaflet tissue incubated with Ang II decreased tissue extensibility in the radial direction, but not in the circumferential direction. Elevated cyclic pressure decreased extensibility in both the radial and circumferential directions. Ang II and elevated cyclic pressure both increased the collagen content in leaflet tissue. Interstitial cells incubated with Ang II were stiffer than those incubated without Ang II while elevated cyclic pressure caused a decrease in cell stiffness. The results of the current study demonstrated that both pressure and Ang II play a role in altering the biomechanical properties of aortic valve leaflets. Ang II and elevated cyclic pressure decreased the extensibility of aortic valve leaflet tissue. Ang II induced direction specific changes in extensibility, demonstrating different response mechanisms. These findings help to provide a better understanding of the responses of aortic valves to mechanical and biochemical changes that occur under hypertensive conditions.

Developmental regulation of ACE gene expression by endogenous kinins and angiotensin II

1995 ◽  
Vol 269 (2) ◽  
pp. F172-F179 ◽  
Author(s):  
I. V. Yosipiv ◽  
S. S. el-Dahr
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Kidney Development ◽  
Developmental Regulation ◽  
Developmental Expression ◽  
Ang Ii ◽  
Adult Rats ◽  
Ace Gene ◽  
Hoe 140 ◽  
Ace Activity

Angiotensin converting enzyme (ACE, i.e., kininase II), a key regulator of kinins and angiotensin II (ANG II) generation, is developmentally regulated and its expression is induced at a specific time point (day 15) of postnatal kidney development. The present study tested the hypothesis that endogenous kinins and ANG II regulate the developmental expression of the renal ACE gene. In the first protocol, newborn rats received the kallikrein inhibitor, aprotinin (100,000 KIU.kg-1.day-1 sc), or the kinin B2 receptor antagonist, HOE-140 (600 micrograms.kg-1.day-1 sc), or 0.9% saline, from birth until postnatal days 5, 15, or 20. Aprotinin prevented the postnatal rise in renal kallikrein activity without affecting blood pressure in either developing or adult rats. Chronic kallikrein blockade significantly attenuated the postnatal induction of both serum ACE activity (-11% vs. controls) and kidney ACE activity and mRNA (-50% vs. controls). In addition, aprotinin attenuated the postnatal rise of ACE activity in the developing lungs. Kidney renin mRNA and ANG II contents were not altered by aprotinin. HOE-140 also attenuated the postnatal rise in kidney ACE mRNA (-25%) and activity (-40%) without affecting blood pressure. Infusion of aprotinin or HOE-140 via osmotic minipumps for 7 days in adult rats was not associated with any changes in renal or pulmonary ACE.(ABSTRACT TRUNCATED AT 250 WORDS)

Intrarenal suppression of angiotensin II type 1 receptor binding molecule in angiotensin II-infused mice

2010 ◽  
Vol 299 (5) ◽  
pp. F991-F1003 ◽  
Author(s):  
Hiromichi Wakui ◽  
Kouichi Tamura ◽  
Miyuki Matsuda ◽  
Yunzhe Bai ◽  
Toru Dejima ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Angiotensin Ii ◽  
Ang Ii ◽  
Significant Suppression ◽  
Outer Medulla ◽  
Α Subunit ◽  
Angiotensinogen Gene

ATRAP [ANG II type 1 receptor (AT1R)-associated protein] is a molecule which directly interacts with AT1R and inhibits AT1R signaling. The aim of this study was to examine the effects of continuous ANG II infusion on the intrarenal expression and distribution of ATRAP and to determine the role of AT1R signaling in mediating these effects. C57BL/6 male mice were subjected to vehicle or ANG II infusions at doses of 200, 1,000, or 2,500 ng·kg−1·min−1 for 14 days. ANG II infusion caused significant suppression of ATRAP expression in the kidney but did not affect ATRAP expression in the testis or liver. Although only the highest ANG II dose (2,500 ng·kg−1·min−1) provoked renal pathological responses, such as an increase in the mRNA expression of angiotensinogen and the α-subunit of the epithelial sodium channel, ANG II-induced decreases in ATRAP were observed even at the lowest dose (200 ng·kg−1·min−1), particularly in the outer medulla of the kidney, based on immunohistochemical staining and Western blot analysis. The decrease in renal ATRAP expression by ANG II infusion was prevented by treatment with the AT1R-specific blocker olmesartan. In addition, the ANG II-mediated decrease in renal ATRAP expression through AT1R signaling occurred without an ANG II-induced decrease in plasma membrane AT1R expression in the kidney. On the other hand, a transgenic model increase in renal ATRAP expression beyond baseline was accompanied by a constitutive reduction of renal plasma membrane AT1R expression and by the promotion of renal AT1R internalization as well as the decreased induction of angiotensinogen gene expression in response to ANG II. These results suggest that the plasma membrane AT1R level in the kidney is modulated by intrarenal ATRAP expression under physiological and pathophysiological conditions in vivo.

Contrasting effects of vasopressin and angiotensin II on rabbit aortic baroreceptors

1991 ◽  
Vol 260 (3) ◽  
pp. H811-H820 ◽  
Author(s):  
P. A. Munch ◽  
J. C. Longhurst
Keyword(s):  
Angiotensin Ii ◽  
Sine Wave ◽  
Ang Ii ◽  
Baroreflex Control ◽  
Pressure Discharge ◽  
Mean Pressure ◽  
Peripheral Effect ◽  
The Media ◽  
Discharge Curves

Arginine vasopressin (AVP) reportedly enhances, whereas angiotensin II (ANG II) attenuates, baroreflex control of the circulation. Here we examine whether these responses can be attributed, in part, to local actions on myelinated baroreceptor (BR) afferents, either directly or via changes in vascular tone. An in vitro rabbit aortic arch/aortic nerve preparation was used to study regularly discharging presumably myelinated BRs under controlled static and pulsatile pressures. At constant suprathreshold pressures, AVP (10(-13) M to 10(-6) M) had no effect on arch diameter or BR frequency, whereas equimolar concentrations of ANG II evoked dose-dependent vasoconstriction and associated BR inhibition. Differences were not caused by limited diffusion to BR endings lying outside the media, since similar results were obtained with either luminal or adventitial applications. AVP also had no effect on diameter or discharge in arches preconstricted with norepinephrine, whereas acetylcholine (ACh) relaxed the arch and thereby increased BR activity. These results eliminate possible AVP-induced endothelium-dependent vasodilation or potentiation of adrenergic vasoconstriction that would not be evident in isolated arches lacking tone. Finally, AVP did not sensitize BRs to changes in pressure, since ramp-evoked pressure-discharge curves remained constant and pulsatile discharge in response to sine-wave pressure inputs was unaltered. ANG II, however, shifted pressure-discharge curves to higher pressures and, with pulsatile inputs at constant mean pressure, reduced peak and average discharge firing rates. In conclusion, AVP has no apparent peripheral effect on aortic myelinated BRs in rabbits that could contribute to amplification of the baroreflex when AVP levels are elevated. In contrast, ANG II can inhibit BR firing as a consequence of local vasoconstriction, which may contribute to attenuation of the reflex when ANG II levels are elevated.

Effects of angiotensin II on cultured rat renomedullary interstitial cells are mediated by AT1A receptors

1996 ◽  
Vol 271 (5) ◽  
pp. F1020-F1028 ◽  
Author(s):  
C. Maric ◽  
G. P. Aldred ◽  
A. M. Antoine ◽  
R. G. Dean ◽  
E. Eitle ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Angiotensin Ii ◽  
Interstitial Cells ◽  
Receptor Subtype ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Vasoactive Peptides ◽  
Polymerase Chain ◽  
Second Messenger Pathways

Renomedullary interstitial cells (RMICs) are prominent in the inner medullary interstitium and have binding sites for several vasoactive agents, including angiotensin II (ANG II). Although the functional role of RMICs remains largely unknown, it is likely that the interaction between RMICs and vasoactive peptides is important in the regulation of renal function. The current investigation characterizes the cellular responses following treatment of RMICs with ANG II. Studies were performed on RMICs isolated from Sprague-Dawley rat kidneys. 125I-labeled [Sar1,Ile8]ANG II specifically bound to RMICs at sites determined by reverse transcription-polymerase chain reaction to be of the AT1A subtype. ANG II (10(-6) and 10(-10) M) had no effect on either basal or forskolin-stimulated adenosine 3',5'-cyclic monophosphate accumulation in RMICs but increased intracellular inositol 1,4,5-trisphosphate concentration after 10 s and intracellular calcium concentration after 18 s. For RMICs plated at low densities, ANG II (10(-6) M) induced an increase in [3H]thymidine incorporation, mediated through the AT1-receptor subtype. For RMICs plated at high densities, ANG II (10(-6) M) induced an increase in extracellular matrix synthesis as detected by trans-35S incorporation, an effect also mediated by AT1 receptors. We conclude that ANG II AT1A receptors on cultured RMICs are coupled to intracellular second messenger pathways leading to hyperplasia and synthesis of extracellular matrix.

scholarly journals The Effects of Angiotensin II or Angiotensin 1-7 on Rat Pial Microcirculation during Hypoperfusion and Reperfusion Injury: Role of Redox Stress

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1861
Author(s):  
Dominga Lapi ◽  
Maurizio Cammalleri ◽  
Massimo Dal Monte ◽  
Martina Di Maro ◽  
Maria Rosaria Santillo ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Reperfusion Injury ◽  
Ang Ii ◽  
Capillary Perfusion ◽  
Redox Stress ◽  
Microvascular Damage ◽  
Protein Receptor ◽  
Induced Changes ◽  
Species Production

Renin–angiotensin systems produce angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7), which are able to induce opposite effects on circulation. This study in vivo assessed the effects induced by Ang II or Ang 1-7 on rat pial microcirculation during hypoperfusion–reperfusion, clarifying the mechanisms causing the imbalance between Ang II and Ang 1-7. The fluorescence microscopy was used to quantify the microvascular parameters. Hypoperfusion and reperfusion caused vasoconstriction, disruption of blood–brain barrier, reduction of capillary perfusion and an increase in reactive oxygen species production. Rats treated with Ang II showed exacerbated microvascular damage with stronger vasoconstriction compared to hypoperfused rats, a further increase in leakage, higher decrease in capillary perfusion and marker oxidative stress. Candesartan cilexetil (specific Ang II type 1 receptor (AT1R) antagonist) administration prior to Ang II prevented the effects induced by Ang II, blunting the hypoperfusion–reperfusion injury. Ang 1-7 or ACE2 activator administration, preserved the pial microcirculation from hypoperfusion–reperfusion damage. These effects of Ang 1-7 were blunted by a Mas (Mas oncogene-encoded protein) receptor antagonist, while Ang II type 2 receptor antagonists did not affect Ang 1-7-induced changes. In conclusion, Ang II and Ang 1-7 triggered different mechanisms through AT1R or MAS receptors able to affect cerebral microvascular injury.

scholarly journals AT1 and AT2 receptors modulate renal tubular cell necroptosis in angiotensin II-infused renal injury mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yongjun Zhu ◽  
Hongwang Cui ◽  
Jie Lv ◽  
Haiqin Liang ◽  
Yanping Zheng ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Injury ◽  
Critical Role ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Tubular Cell ◽  
Tubular Damage ◽  
Renal Tubular Cell ◽  
Ang Ii ◽  
Renal Tubular

AbstractAbnormal renin-angiotensin system (RAS) activation plays a critical role in the initiation and progression of chronic kidney disease (CKD) by directly mediating renal tubular cell apoptosis. Our previous study showed that necroptosis may play a more important role than apoptosis in mediating renal tubular cell loss in chronic renal injury rats, but the mechanism involved remains unknown. Here, we investigate whether blocking the angiotensin II type 1 receptor (AT1R) and/or angiotensin II type 2 receptor (AT2R) beneficially alleviates renal tubular cell necroptosis and chronic kidney injury. In an angiotensin II (Ang II)-induced renal injury mouse model, we found that blocking AT1R and AT2R effectively mitigates Ang II-induced increases in necroptotic tubular epithelial cell percentages, necroptosis-related RIP3 and MLKL protein expression, serum creatinine and blood urea nitrogen levels, and tubular damage scores. Furthermore, inhibition of AT1R and AT2R diminishes Ang II-induced necroptosis in HK-2 cells and the AT2 agonist CGP42112A increases the percentage of necroptotic HK-2 cells. In addition, the current study also demonstrates that Losartan and PD123319 effectively mitigated the Ang II-induced increases in Fas and FasL signaling molecule expression. Importantly, disruption of FasL significantly suppressed Ang II-induced increases in necroptotic HK-2 cell percentages, and necroptosis-related proteins. These results suggest that Fas and FasL, as subsequent signaling molecules of AT1R and AT2R, might involve in Ang II-induced necroptosis. Taken together, our results suggest that Ang II-induced necroptosis of renal tubular cell might be involved both AT1R and AT2R and the subsequent expression of Fas, FasL signaling. Thus, AT1R and AT2R might function as critical mediators.

Pharmacological blockage of ICAM-1 improves angiotensin II-induced cardiac remodeling by inhibiting adhesion of LFA-1+ monocytes

2019 ◽  
Vol 317 (6) ◽  
pp. H1301-H1311 ◽  
Author(s):  
Qiu-Yue Lin ◽  
Ping-Ping Lang ◽  
Yun-Long Zhang ◽  
Xiao-Lei Yang ◽  
Yun-Long Xia ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiovascular Diseases ◽  
Adhesion Molecules ◽  
Vascular Endothelium ◽  
Cardiac Remodeling ◽  
Leukocyte Adhesion ◽  
Neutralizing Antibody ◽  
Ang Ii ◽  
Cardiac Contractile ◽  
And Migration

Intercellular adhesion molecule-1 (ICAM-1) is a member of an immunoglobulin-like superfamily of adhesion molecules that mediate leukocyte adhesion to vascular endothelium and are involved in several cardiovascular diseases, including ischemia-reperfusion injury, myocardial infarction, and atherosclerosis. However, the role of ICAM-1 in angiotensin II (ANG II)-induced cardiac remodeling in mice remains unclear. Wild-type mice were administered an IgG control or ICAM-1 neutralizing antibody (1 and 2 mg/mouse, respectively) and ANG II (1,000 ng·kg−1·min−1) for up to 14 days. Cardiac contractile function and structure were detected by echocardiography. Hypertrophy, fibrosis, and inflammation were assessed by histological examination. The infiltration of lymphocyte function-associated antigen-1 (LFA-1+) monocytes/macrophages was assessed by immunostaining. The mRNA expression of genes was evaluated by quantitative RT-PCR analysis. Protein levels were tested by immunoblotting. We found that ICAM-1 expression in ANG II-infused hearts and ICAM-1 levels in serum from human patients with heart failure were significantly increased. Moreover, ANG II infusion markedly enhanced ANG II-induced hypertension, caused cardiac contractile dysfunction, and promoted cardiac hypertrophy, fibrosis, and LFA-1+ macrophage infiltration. Conversely, blockage of ICAM-1 with a neutralizing antibody dose-dependently attenuated these effects. Moreover, our in vitro data further demonstrated that blocking ICAM-1 inhibited ANG II-induced LFA-1+ macrophage adhesion to endothelial cells and migration. In conclusion, these results provide novel evidence that blocking ICAM-1 exerts a protective effect in ANG II-induced cardiac remodeling at least in part through the modulation of adhesion and infiltration of LFA-1+ macrophages in the heart. Inhibition of ICAM-1 may represent a new therapeutic approach for hypertrophic heart diseases. NEW & NOTEWORTHY Leukocyte adhesion to vascular endothelium is a critical step in cardiovascular diseases. ICAM-1 is a member of immunoglobulin-like superfamily of adhesion molecules that binds LFA-1 to mediate leukocytes adhesion and migration. However, the significance of ICAM-1 in ANG II-induced cardiac remodeling remains unclear. This study reveals that blocking of ICAM-1 prevents ANG II-induced cardiac remodeling via modulating adhesion and migration of LFA-1+ monocytes, may serve as a novel therapeutic target for hypertensive cardiac diseases.

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.

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