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.

Role of angiotensin II and catecholamines in blood pressure variability responses to stress in SHR

1996 ◽  
Vol 270 (6) ◽  
pp. R1265-R1272 ◽  
Author(s):  
E. Gaudet ◽  
J. Blanc ◽  
J. L. Elghozi
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Acute Administration ◽  
Angiotensin Ii Receptor ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Air Jet ◽  
Wistar Kyoto

The contribution of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) to blood pressure (BP) and heart rate (HR) variability responses to air-jet stress was assessed in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Activity of the encogenous RAS was suppressed by chronic treatment by a nonpeptide angiotensin II receptor antagonist (Iosartan). The role of alpha 1-adrenoceptor activity was evaluated in rats by acute administration of prazosin. In untreated animals, an air jet induced an increase in systolic BP (SBP; 9 +/- 2 mmHg for WKY and 8 +/- 2 mmHg for SHR) and in HR (56 +/- 19 beats/min for WKY and 76 +/- 8 beats/min for SHR), followed by an increase of the midfrequency (MF; 0.2-0.6 Hz) component of HR in WKY (183%) and by an increase of the MF component of SBP and diastolic BP in SHR (65%). Prazosin prevented BP rises as well as the MF component of BP and HR increases associated with air-jet stress. Chronic suppression of the RAS by losartan did not alter the BP response to the air jet in WKY and slightly reduced it in SHR but abolished all the BP and HR variability changes in both strains. These results indicate that the SNS but not RAS is essential for the BP rise induced by stress and demonstrate that RAS in conjunction with SNS is involved in BP and HR variability changes associated with stress.

Physiological persona differences based on stress and inflammation between meditators and healthy controls

2019 ◽  
Vol 17 (2) ◽  
Author(s):  
Dipti Magan ◽  
Raj Kumar Yadav
Keyword(s):  
Blood Pressure ◽  
Body Mass Index ◽  
Plasma Levels ◽  
Inflammatory Markers ◽  
Tumor Necrosis ◽  
Healthy Controls ◽  
Short Term ◽  
Tnf Α ◽  
Necrosis Factor

AbstractBackgroundNowadays, yoga is endorsed and advised routinely to stay fit and healthy, as well as control many chronic diseases including diabetes type 2, hypertension, coronary artery diseases, etc. Now, our assumption is that those who do regular yoga have different persona than who do not do yoga regularly. We planned to test our hypothesis scientifically, and therefore baseline physiological characteristics with stress and inflammation levels in long-term and short-term meditators and healthy novice controls were analyzed.MethodsIn this retrospective analysis, 97 male participants were included for their Baseline analysis. Fifteen apparently healthy subjects practicing preksha meditation (since >5 years, at least 5 days a week) were included as long-term meditators (LTMs); 58 subjects who attended one of our short-term yoga-based lifestyle intervention programs for 2 weeks were included as short-term meditators (STMs); 24 male novice subjects, who did not participate in any yogic intervention, were included as healthy controls. Here, we analyzed the Baseline plasma levels of stress and inflammatory markers, cortisol, β-endorphin, interleukin (IL)-6 and tumor necrosis factor (TNF)-α in long-term meditators vs. short-term meditators vs. healthy controls.Outcome measuresThe study parameters body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), plasma levels of stress and immune markers, cortisol, β-endorphin (β-Ed), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were assessed in all the three groups at baseline.ResultsSignificant (p<0.05) differences were observed at baseline for plasma levels of stress and inflammatory markers as well as body mass index and systolic blood pressure among LTM vs. STM vs. healthy controls.ConclusionsOur observations suggest that the subjects who do regular yoga-meditation practice have better stress & inflammation status than comparable age matched healthy controls.

scholarly journals The effects of phentolamine on fructose-fed rats

2012 ◽  
Vol 90 (8) ◽  
pp. 1075-1085 ◽  
Author(s):  
Kangbin Zhou ◽  
Ujendra Kumar ◽  
Violet G. Yuen ◽  
John H. McNeill
Keyword(s):  
Blood Pressure ◽  
Uric Acid ◽  
Angiotensin Ii ◽  
Plasma Levels ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Medical Disorders ◽  
Dietary Fructose ◽  
Plasma Nitrate

Metabolic syndrome (MS) is a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes. MS is associated with obesity, increased blood pressure, hyperlipidemia, and hyperglycemia. This study was designed to investigate the pharmacological profile of phentolamine, a nonselective α adrenergic receptor antagonist, in the prevention of increased blood pressure in fructose-fed rats. Phentolamine prevented the fructose-induced increase in systolic blood pressure without affecting insulin sensitivity and major metabolic parameters. The levels of plasma noradrenaline and angiotensin II, 2 proposed contributors to the development of fructose-induced elevated blood pressure, were examined. Neither noradrenaline nor angiotensin II levels were affected by phentolamine treatment. Since overproduction of nitric oxide has been shown to lead to an elevation in peroxynitrite, the role of oxidative stress, a proposed mechanism of fructose-induced elevated blood pressure and insulin resistance, was examined by measuring plasma levels of total nitrate/nitrite. Plasma nitrate/nitrite was significantly elevated in all fructose-fed animals, regardless of treatment with phentolamine. Another proposed contributor toward fructose-induced MS is an elevation in uric acid levels. In this experiment, plasma levels of uric acid were found to be increased by dietary fructose and were unaffected by phentolamine treatment.

Luteolin Reduces Blood Pressure via Down-regulation of Renal Angiotensin II Receptor and Mineralocorticoid Receptor Expressions in Rats Co-exposed to Diclofenac and Sodium Fluoride

2021 ◽  
Author(s):  
Temitayo Olabisi Ajibade ◽  
Akinleye Stephen AKINRINDE ◽  
Moses Olusola Adetona ◽  
Ademola Adetokunbo Oyagbemi ◽  
Aduragbenro Deborah A. Adedapo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Sodium Fluoride ◽  
Antioxidant Status ◽  
Renal Toxicity ◽  
Protein Carbonyls ◽  
Angiotensin Ii Receptor ◽  
Male Wistar Rats ◽  
Renal Expression

Abstract This study was designed to investigate the modulatory role of Luteolin (Lut) on haemodynamic parameters and the potential mechanisms involving renal Angiotensin II (AT2R) and Mineralocorticoid (MCR) receptors in renal toxicity induced by co-exposure to Diclofenac (Dcf) and sodium fluoride (NaF) in rats. Male Wistar rats were administered with either vehicle (control), Dcf only (9 mg/kg orally) or concurrently with NaF (300 ppm in drinking water). Other groups were treated with LutA (100 mg/kg) or LutB (200 mg/kg) along with Dcf and NaF exposures. All treatments lasted 8 days, following which blood pressure indices were measured using tail-cuff plethysmography. Renal expressions of AT2R and MCR were studied with immunohistochemistry, while biomarkers of oxidative and antioxidant status were also measured in the kidneys. Systolic, diastolic and mean arterial pressures were significantly (p<0.05) reduced in Dcf-treated rats, compared to control values. However, co-treatment with NaF or Lut restored these parameters. While the expression of AT2R and MCR was high in the Dcf and Dcf+NaF groups, treatment with Lut caused obvious reduction in the renal expression of these receptors. Increased lipid peroxidation (Malondialdehyde) and protein oxidation (protein carbonyls) with a lowering of reduced glutathione levels contributed to the renal toxicity of Dcf, which was significantly ameliorated in Lut-treated rats. The protective effect of Lut on blood pressure was probably mediated by stimulation of renal expressions of AT2R and MCR, reduction of oxidative stress and an improvement of renal antioxidant status.

Piper sarmentosum Roxb. Root Extracts Confer Neuroprotection by Attenuating Beta Amyloid-Induced Pro-Inflammatory Cytokines Released from Microglial Cells

2019 ◽  
Vol 16 (3) ◽  
pp. 251-260 ◽  
Author(s):  
Elaine Wan Ling Chan ◽  
Emilia Tze Ying Yeo ◽  
Kelly Wang Ling Wong ◽  
Mun Ling See ◽  
Ka Yan Wong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Mrna Expression ◽  
Inflammatory Mediators ◽  
Beta Amyloid ◽  
Microglial Cells ◽  
Root Extracts ◽  
Tnf Α ◽  
P38α Mapk ◽  
Anti Inflammatory ◽  
Bv2 Microglial Cells

<P>Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive, increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are associated with AD. Piper sarmentosum Roxb. (PS) is a medicinal plant reported to possess various biological properties, including anti-inflammatory, anti-psychotic and anti-oxidant activity. However, little is known about the anti-inflammatory activity of PS roots despite their traditional use to treat inflammatory- mediated ailments. Objective: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts obtained from the roots of PS against beta-amyloid (Aβ)-induced microglial toxicity associated with the production of pro-inflammatory mediators. Method: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate (REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aβ. The production and mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay. BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective effect was assessed using MTT assay. Results: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression of IL-1β, IL-6 and TNF-α in Aβ-induced BV2 microglial cells. In addition, RHXN, REA and RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in microglia. Importantly, PS root extracts have protective effects against Aβ-induced indirect neurotoxicity either by inhibiting the production of NO, IL-1β, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y cells against these inflammatory mediators. Conclusions: These findings provided evidence that PS root extracts confer neuroprotection against Aβ- induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a potential therapeutic agent for inflammation-related neurological conditions including Alzheimer’s disease (AD).</P>

Anti-Hypertensive Potential and Epigenetics of Angiotensin II type 2 Receptor (AT2R)

2020 ◽  
Vol 16 ◽  
Author(s):  
Mayank Chaudhary
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Blood Pressure Regulation ◽  
Biologically Active ◽  
Pressure Regulation ◽  
Tissue Remodelling ◽  
Critical Pathway

Background:: Renin angiotensin system (RAS) is a critical pathway involved in blood pressure regulation. Octapeptide, angiotensin II (Ang aII), is biologically active compound of RAS pathway which mediates its action by binding to either angiotensin II type 1 receptor (AT1R) or angiotensin II type 2 receptor (AT2R). Binding of Ang II to AT1R facilitates blood pressure regulation whereas AT2R is primarily involved in wound healing and tissue remodelling. Objective:: Recent studies have highlighted additional role of AT2R to counter balance detrimental effects of AT1R. Activation of angiotensin II type 2 receptor using AT2R agonist has shown effect on natriuresis and release of nitric oxide. Additionally, AT2R activation has been found to inhibit angiotensin converting enzyme (ACE) and enhance angiotensin receptor blocker (ARB) activity. These findings highlight the potential of AT2R as novel therapeutic target against hypertension. Conclusion:: The potential role of AT2R highlights the importance of exploring additional mechanisms that might be crucial for AT2R expression. Epigenetic mechanisms including DNA methylation and histone modification have been explored vastly with relation to cancer but role of such mechanisms on expression of AT2R has recently gained interest.

scholarly journals Plasma and cerebrospinal fluid inflammation and the blood-brain barrier in older surgical patients: the Role of Inflammation after Surgery for Elders (RISE) study

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Sarinnapha M. Vasunilashorn ◽  
◽  
Long H. Ngo ◽  
Simon T. Dillon ◽  
Tamara G. Fong ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Plasma Levels ◽  
Inflammatory Markers ◽  
Brain Barrier ◽  
Markers Of Inflammation ◽  
Blood Brain ◽  
Csf Levels ◽  
The Relationship

Abstract Background Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surgery, we aimed to examine whether surgery compromises the blood-brain barrier (BBB), evaluate postoperative changes in inflammatory markers, and assess the correlations between plasma and CSF levels of inflammation. Methods We examined the Role of Inflammation after Surgery for Elders (RISE) study of adults aged ≥ 65 who underwent elective hip or knee surgery under spinal anesthesia who had plasma and CSF samples collected at baseline and postoperative 1 month (PO1MO) (n = 29). Plasma and CSF levels of three inflammatory markers previously identified as increasing after surgery were measured using enzyme-linked immunosorbent assay: interleukin-6 (IL-6), C-reactive protein (CRP), and chitinase 3-like protein (also known as YKL-40). The integrity of the BBB was computed as the ratio of CSF/plasma albumin levels (Qalb). Mean Qalb and levels of inflammation were compared between baseline and PO1MO. Spearman correlation coefficients were used to determine the correlation between biofluids. Results Mean Qalb did not change between baseline and PO1MO. Mean plasma and CSF levels of CRP and plasma levels of YKL-40 and IL-6 were higher on PO1MO relative to baseline, with a disproportionally higher increase in CRP CSF levels relative to plasma levels (CRP tripled in CSF vs. increased 10% in plasma). Significant plasma-CSF correlations for CRP (baseline r = 0.70 and PO1MO r = 0.89, p < .01 for both) and IL-6 (PO1MO r = 0.48, p < .01) were observed, with higher correlations on PO1MO compared with baseline. Conclusions In this elective surgical sample of older adults, BBB integrity was similar between baseline and PO1MO, plasma-CSF correlations were observed for CRP and IL-6, plasma levels of all three markers (CRP, IL-6, and YKL-40) increased from PREOP to PO1MO, and CSF levels of only CRP increased between the two time points. Our identification of potential promising plasma markers of inflammation in the CNS may facilitate the early identification of patients at greatest risk for neuroinflammation and its associated adverse cognitive outcomes.

Sign in / Sign up

Export Citation Format

Share Document