Angiotensin II increases macrophage uptake of Ox-LDL and CD36 mRNA expression: Possible role of IL-6 and inhibitory effects of fosinopril and losartan

2000 ◽  
Vol 151 (1) ◽  
pp. 30
Author(s):  
S Keidar ◽  
P Heinrich
Keyword(s):  
Angiotensin Ii ◽  
Mrna Expression ◽  
Inhibitory Effects ◽  
Macrophage Uptake

Reactive Oxygen Species-Mediated Homologous Downregulation of Angiotensin II Type 1 Receptor Mrna by Angiotensin II

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 688-688
Author(s):  
Toshihiro Ichiki ◽  
Kotaro Takeda ◽  
Akira Takeshita
Keyword(s):  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Mrna Expression ◽  
Crucial Role ◽  
Oxygen Species ◽  
Ang Ii ◽  
Stimulation Of

58 Recent studies suggest a crucial role of reactive oxygen species (ROS) for the signaling of Angiotensin II (Ang II) through type 1 Ang II receptor (AT1-R). However, the role of ROS in the regulation of AT1-R expression has not been explored. In this study, we examined the effect of an antioxidant on the homologous downregulation of AT1-R by Ang II. Ang II (10 -6 mol/L) decreased AT1-R mRNA with a peak suppression at 6 hours of stimulation in rat aortic vascular smooth muscle cells (VSMC). Ang II dose-dependently (10 -8 -10 -6 ) suppressed AT1-R mRNA at 6 hours of stimulation. Preincubation of VSMC with N-acetylcysteine (NAC), a potent antioxidant, almost completely inhibited the Ang II-induced downregulation of AT1-R mRNA. The effect of NAC was due to stabilization of the AT1-R mRNA that was destabilized by Ang II. Ang II did not affect the promoter activity of AT1-R gene. Diphenylene iodonium (DPI), an inhibitor of NADH/NADPH oxidase failed to inhibit the Ang II-induced AT1-R mRNA downregulation. The Ang II-induced AT1-R mRNA downregulation was also blocked by PD98059, an extracellular signal-regulated protein kinase (ERK) kinase inhibitor. Ang II-induced ERK activation was inhibited by NAC as well as PD98059 whereas DPI did not inhibit it. To confirm the role of ROS in the regulation of AT1-R mRNA expression, VSMC were stimulated with H 2 O 2 . H 2 O 2 suppressed the AT1-R mRNA expression and activated ERK. These results suggest that production of ROS and activation of ERK are critical for downregulation of AT1-R mRNA. The differential effect of NAC and DPI on the downregulation of AT1-R mRNA may suggest the presence of other sources than NADH/NADPH oxidase pathway for ROS in Ang II signaling. Generation of ROS through stimulation of AT1-R not only mediates signaling of Ang II but may play a crucial role in the adaptation process of AT1-R to the sustained stimulation of Ang II.

scholarly journals Effect of AT1 receptor antagonism on vascular and circulating inflammatory mediators in SHR: role of NF-κB/IκB system

2005 ◽  
Vol 288 (1) ◽  
pp. H111-H115 ◽  
Author(s):  
David Sanz-Rosa ◽  
M. Pilar Oubiña ◽  
Eva Cediel ◽  
Natalia de las Heras ◽  
Onofre Vegazo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Mrna Expression ◽  
Inflammatory Mediators ◽  
Plasma Levels ◽  
Inflammatory Markers ◽  
Angiotensin Ii Receptor ◽  
Tnf Α ◽  
Wistar Kyoto

We investigated the role of angiotensin II in vascular and circulating inflammatory markers in spontaneously hypertensive rats (SHR). IL-1β, IL-6, and TNF-α aortic mRNA expression and plasma levels were measured in adult SHR untreated or treated with the angiotensin II receptor antagonist candesartan (2 mg·kg−1·day−1) or antihypertensive triple therapy (TT; in mg·kg−1·day−1: 20 hydralazine + 7 type 1 hydrochlorothiazide + 0.15 reserpine) for 10 wk. Likewise, aortic expression of NF-κB p50 subunit precursor p105 and its inhibitor (IκB) were measured. Age-matched Wistar-Kyoto rats (WKY) served as normotensive reference. High blood pressure levels were associated with increased ( P < 0.05) aortic mRNA expression of IL-1β, IL-6, and TNF-α. Hypertension was also accompanied by increased IL-1β and IL-6 plasma levels. No differences were observed in circulating TNF-α levels between SHR and WKY. SHR presented elevated aortic mRNA expression of the transcription factor NF-κB and reduction in its inhibitor, IκB. Candesartan decreased ( P < 0.05) blood pressure levels, aortic mRNA expression of IL-1β, IL-6, and TNF-α, and ( P < 0.05) IL-1β and IL-6 plasma concentration. However, although arterial pressure decrease was comparable for the treatments, TT only partially reduced the increments in inflammatory markers. In fact, candesartan-treated rats showed significantly lower levels of circulating and vascular inflammatory markers than TT-treated animals. The treatments increased IκB mRNA expression similarly. However, only candesartan reduced NF-κB mRNA expression. In summary, 1) SHR presented a vascular inflammatory process; 2) angiotensin II, and increased hemodynamic forces associated with hypertension, seems to be involved in stimulation of inflammatory mediators through NF-κB system activation; and 3) reduction of inflammatory mediators produced by candesartan in SHR could be partially due to both downregulation of NF-κB and upregulation of IκB.

P5443NOD2 knock down worsens diastolic dysfunction in murine angiotensin II-induced heart failure

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Mueller ◽  
J Lin ◽  
K Pappritz ◽  
C Tschoepe ◽  
S Van Linthout
Keyword(s):  
Heart Failure ◽  
Immune System ◽  
Angiotensin Ii ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Mrna Expression ◽  
Diastolic Heart Failure ◽  
Knock Down ◽  
Lv Diastolic Dysfunction

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is associated with cardiac inflammatory responses, indicating a potential role of the immune system in the pathology of diastolic dysfunction. The cytoplasmatic pattern recognition receptor, nucleotide binding oligomerization domain 2 (NOD2) belongs to the innate immune system and induces among others the NLRP3 inflammasome, known to be involved in myocarditis and coronary heart disease. Purpose The aim of this study was to explore the role of NOD2 in Angiotensin II (AngII)-induced diastolic heart failure. Methods In NOD2−/− knock down and C57Bl6/j-wild type (WT) mice, diastolic dysfunction was induced by subcutaneous administration of 1.4mg/kg*day–1 AngII. Twenty-one days after first AngII administration, left ventricular (LV) function was evaluated by pressure tip catheter. Cardiac fibrosis, inflammation, and the expression of NOD2 and the NLRP3 component Apoptosis-associated speck like protein containing a caspase recruitment domain (ASC) were determined via immunohistochemistry, real-time PCR or Western Blot. Results LV NOD2 mRNA expression was 2.3-fold (p<0.0005) and 1.9-fold (p<0.0005) lower in NOD2−/− control and NOD2−/− AngII mice compared to their respective WT littermates. In parallel, LV protein expression of the downstream NLRP3 component Apoptosis-associated speck like protein containing a caspase recruitment domain (ASC) was 1.5-fold (p<0.05) lower in NOD2−/− AngII mice versus WT AngII mice, whereas LV protein IL-1β levels were unchanged. LV diastolic dysfunction was more pronounced in NOD2−/− AngII mice versus WT AngII mice, as displayed by a 19% (p<0.05) increased LV relaxation time and 24% (p<0.057) impaired dP/dtmin, with no changes in the ejection fraction (EF: NOD2−/− AngII 72.5%±5.4 versus WT AngII 65.6±3.5). In parallel, LV presence of CD68-positive cells was 1.8-fold (p<0.05) higher in NOD2−/− AngII compared to WT AngII mice. Concomitantly, NOD2−/− AngII mice displayed 1.3-fold (p<0.05) and 1.7-fold (p<0.05) higher LV mRNA expression of the chemokine macrophage inflammatory protein (MIP)-2 and monocyte chemotactant protein (MCP)-1 compared to WT AngII mice, respectively. Furthermore, cardiac interstitial fibrosis in NOD2−/− mice with AngII-induced diastolic dysperformance was more pronounced versus the WT AngII group, as indicated by a 2.0-fold (p<0.0005), 2.0-fold, and 1.6-fold (p<0.05) higher LV ColI/ColIII ratio, and TGF-β and TIMP-1 mRNA expression, respectively. Conclusion NOD2−/− deteriorates LV diastolic dysfunction and worsens pathophysiological key mechanisms in mice with AngII-induced diastolic heart failure.

scholarly journals Collecting duct (pro)renin receptor targets ENaC to mediate angiotensin II-induced hypertension

2017 ◽  
Vol 312 (2) ◽  
pp. F245-F253 ◽  
Author(s):  
Kexin Peng ◽  
Xiaohan Lu ◽  
Fei Wang ◽  
Adam Nau ◽  
Ren Chen ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Protein Expression ◽  
Mrna Expression ◽  
Collecting Duct ◽  
Underlying Mechanism ◽  
Ang Ii ◽  
Induced Hypertension ◽  
Mrna And Protein Expression ◽  
Receptor Targets

The (pro)renin receptor (PRR) is abundantly expressed in the collecting duct (CD) and the expression is further induced by angiotensin II (ANG II). The present study was conducted to investigate the role of CD PRR during ANG II-induced hypertension and to further explore the underlying mechanism. Radiotelemetry demonstrated that a 1-wk ANG II infusion gradually and significantly induced hypertensive response in floxed mice and this response was significantly attenuated in mice lacking PRR in the CD (termed CD PRR KO). ANG II infusion in floxed mice increased urinary renin activity and selectively induced renal medullary α-epithelial sodium channel (α-ENaC) mRNA and protein expression, all of which were blunted in the null mice. In cultured mpkCCD cells grown in Transwells, transepithelial Na+ transport as measured by using a volt-ohmmeter was transiently stimulated by acute ANG II treatment, which was abolished by a PRR antagonist, PRO20. In a chronic setting, ANG II treatment induced α-ENaC mRNA expression in mpkCCD cells, which was similarly blocked by PRO20. Chronic intramedullary infusion of an ENaC inhibitor amiloride in rats significantly attenuated ANG II-induced hypertension. Overall, the present study suggests that CD PRR contributes to ANG II-induced hypertension at least partially via activation of renal medullary ENaC.

scholarly journals Role of AT1 receptors and autonomic nervous system in mediating acute pressor responses to ANG II in anesthetized mice

1999 ◽  
Vol 277 (5) ◽  
pp. E838-E847 ◽  
Author(s):  
Trinity J. Bivalacqua ◽  
Ajay Dalal ◽  
Hunter C. Champion ◽  
Philip J. Kadowitz
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Angiotensin Ii ◽  
Peripheral Resistance ◽  
Inhibitory Effects ◽  
Hemodynamic Responses ◽  
Autonomic Nervous ◽  
Pressor Responses ◽  
Cd1 Mice

Hemodynamic responses to angiotensin II and the role of AT1 and AT2 receptors and the autonomic nervous system in mediating acute responses to angiotensin II were investigated in anesthetized CD1 mice. Injections of angiotensin II caused dose-related increases in systemic arterial pressure that were antagonized by candesartan. Pressor responses to angiotensin II were not altered by PD-123,319 in doses up to 25 mg/kg iv. At the lowest dose studied (20 μg/kg iv), the inhibitory effects of candesartan were competitive, whereas at the highest dose (100 μg/kg iv) the dose-response curve for angiotensin II was shifted to the right in a nonparallel manner with inhibitory effects that could not be surmounted. The inhibitory effects of candesartan were selective and were similar in animals pretreated with enalaprilat (1 mg/kg iv) to reduce endogenous angiotensin II production. Acute pressor responses to angiotensin II were not altered by propranolol (200 μg/kg iv), phentolamine (200 μg/kg iv), or atropine (1 mg/kg iv) but were enhanced by hexamethonium (5 mg/kg iv). Increases in total peripheral resistance induced by angiotensin II were inhibited by the AT1-receptor antagonist but were not altered by AT2-, α-, or β-receptor antagonists. These results suggest that acute pressor responses to angiotensin II are mediated by AT1 receptors, are buffered by the baroreceptors, and are not modulated by effects on AT2 receptors and that activation of the sympathetic nervous system plays little if any role in mediating rapid hemodynamic responses to the peptide in anesthetized CD1 mice.

scholarly journals Increased intracellular Ca2+ selectively suppresses IL-1-induced NO production by reducing iNOS mRNA stability.

1995 ◽  
Vol 129 (6) ◽  
pp. 1651-1657 ◽  
Author(s):  
Y Geng ◽  
M Lotz
Keyword(s):  
Mrna Expression ◽  
Mrna Stability ◽  
Articular Chondrocytes ◽  
Cyclopiazonic Acid ◽  
Inos Mrna ◽  
No Production ◽  
Mrna Levels ◽  
Inhibitory Effects ◽  
No Release

This study addresses the role of intracellular calcium (Ca2+) in the expression of iNOS, an IL-1 inducible gene in human articular chondrocytes. The calcium ionophore A23187 and ionomycin did not induce NO release or iNOS expression but inhibited dose dependently IL-1-induced NO release with IC50 of 200 nM and 100 nM, respectively. Increased intracellular Ca2+ induced by thapsigargin or cyclopiazonic acid, inhibitors of the endoplasmic reticulum Ca2+ ATPase, had similar inhibitory effects with IC50 of 1 nM and 3 microM, respectively. LPS and TNF alpha induced NO production were also suppressed by these Ca2+ elevating drugs. Levels of IL-1-induced iNOS protein were reduced by A23187, thapsigargin, and cyclopiazonic acid. These drugs as well as Bay K 8644 and KCl inhibited IL-1-induced iNOS mRNA expression. To analyze the role of Ca2+ in the expression of other IL-1 responsive genes in chondrocytes, these Ca2+ modulating drugs were tested for effects on COXII. In contrast to the inhibitory effects on iNOS mRNA, these drugs induced COXII mRNA expression and in combination with IL-1, enhanced COXII mRNA levels. Ca2+ mediated increases in COXII mRNA expression were associated with an increase in COXII protein. The kinetics of Ca2+ effects on IL-1-induced iNOS mRNA levels suggested a posttranscriptional mechanism. Analysis of iNOS mRNA half life showed that it was 6-7 h in IL-1-stimulated cells and decreased by A23187 to 2-3 h. In conclusion, these results show that Ca2+ inhibits IL-1-induced NO release, iNOS protein, and mRNA expression in human articular chondrocytes by reducing iNOS mRNA stability. Under identical conditions increased Ca2+ enhances IL-1-induced COXII gene and protein expression.

Antagonists of EDRF attenuate acetylcholine-induced vasodilation in isolated hamster lungs

1992 ◽  
Vol 72 (6) ◽  
pp. 2162-2167 ◽  
Author(s):  
C. M. Tseng ◽  
W. Mitzner
Keyword(s):  
Methylene Blue ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Krebs Solution ◽  
Inhibitory Effects ◽  
Relaxing Factor ◽  
Prostaglandin F2 Alpha ◽  
Pressor Responses

To evaluate the role of endothelium-dependent relaxing factor (EDRF) in acetylcholine- (ACh) induced vasodilation in the intact pulmonary circulation, we examined the effects of atropine and three EDRF antagonists that have been shown to be effective in vitro: nitro-L-arginine (NOARG), hemoglobin (Hb), and methylene blue (MB). We studied ACh-induced dilation after preconstriction with angiotensin II and prostaglandin F2 alpha (PGF2 alpha) in hamster lungs perfused with Krebs solution containing Ficoll (4 g/dl) and indomethacin (10 microM). In the constricted lungs with no blockers, infusion of ACh (1 microM) decreased the constriction by 67%, and this effect was completely abolished by atropine pretreatment (1 microM). Treatment of hamster lungs with each of the three EDRF blockers, NOARG (30 microM), Hb (10 microM), and MB (250 microM), augmented the pressor responses to angiotensin II and PGF2 alpha. However, NOARG and MB inhibited the ACh-induced dilation by 49 and 60%, respectively, without affecting vasodilatory responses to isoproterenol, an agent that relaxes vascular smooth muscle independent of EDRF synthesis. In contrast, Hb significantly inhibited both ACh- and isoproterenol-induced vasodilations. Because all these EDRF antagonists attenuated ACh-induced vasodilation in intact hamster lungs, we conclude that EDRF plays a role in this response. Nonselective inhibitory effects of Hb in hamster lungs, however, suggest that mechanisms other than inhibition of EDRF by this agent are also involved.

scholarly journals Arsenic trioxide and angiotensin II have inhibitory effects on HERG protein expression: Evidence for the role of PML SUMOylation

Oncotarget ◽  
2017 ◽  
Vol 8 (28) ◽  
pp. 45447-45458 ◽  
Author(s):  
Yu Liu ◽  
Duo Li ◽  
Dan Nie ◽  
Shang-Kun Liu ◽  
Fang Qiu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Protein Expression ◽  
Arsenic Trioxide ◽  
Inhibitory Effects ◽  
Expression Evidence
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