scholarly journals Butterfly Pea Flower (Clitoria ternatea Linn.) Extract Ameliorates Cardiovascular Dysfunction and Oxidative Stress in Nitric Oxide-Deficient Hypertensive Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 523
Author(s):  
Putcharawipa Maneesai ◽  
Metee Iampanichakul ◽  
Nisita Chaihongsa ◽  
Anuson Poasakate ◽  
Prapassorn Potue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Vascular Dysfunction ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Sprague Dawley ◽  
Necrosis Factor Alpha ◽  
Clitoria Ternatea ◽  
Plasma Nitrate

In this study, we examine whether Clitoria ternatea Linn. (CT) can prevent Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced cardiac and vascular dysfunction in rats. Male Sprague Dawley rats were given L-NAME (40 mg/kg, drinking water) and orally administered with CT extract (300 mg/kg/day) or lisinopril (2.5 mg/kg/day) for 5 weeks. The main phytochemical components of the CT extract were found to be flavonoids. The CT extract alleviated the high blood pressure in rats receiving L-NAME. Decreased vasorelaxation responses to acetylcholine and enhanced contractile responses to sympathetic nerve stimulation in aortic rings and mesenteric vascular beds of L-NAME treated rats were ameliorated by CT extract supplementation. Left ventricular hypertrophy and dysfunction were developed in L-NAME rats, which were partially prevented by CT extract treatment. The CT extract alleviated upregulated endothelial nitric oxide synthase expression, decreased plasma nitrate/nitrite levels, and increased oxidative stress in L-NAME rats. It suppressed high levels of serum angiotensin-converting enzyme activity, plasma angiotensin II, and cardiac angiotensin II type 1 receptor, NADPH oxidases 2, nuclear factor-kappa B, and tumor necrosis factor-alpha expression. The CT extract, therefore, partially prevented L-NAME-induced hypertension and cardiovascular alterations in rats. These effects might be related to a reduction in the oxidative stress and renin–angiotensin system activation due to L-NAME in rats.

scholarly journals Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia

2008 ◽  
Vol 295 (4) ◽  
pp. F1134-F1141 ◽  
Author(s):  
Laura G. Sánchez-Lozada ◽  
Virgilia Soto ◽  
Edilia Tapia ◽  
Carmen Avila-Casado ◽  
Yuri Y. Sautin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Uric Acid ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Systemic Hypertension ◽  
Sprague Dawley ◽  
Renal Vasoconstriction ◽  
Renal Abnormalities ◽  
Oxonic Acid

Endothelial dysfunction is a characteristic feature during the renal damage induced by mild hyperuricemia. The mechanism by which uric acid reduces the bioavailability of intrarenal nitric oxide is not known. We tested the hypothesis that oxidative stress might contribute to the endothelial dysfunction and glomerular hemodynamic changes that occur with hyperuricemia. Hyperuricemia was induced in Sprague-Dawley rats by administration of the uricase inhibitor, oxonic acid (750 mg/kg per day). The superoxide scavenger, tempol (15 mg/kg per day), or placebo was administered simultaneously with the oxonic acid. All groups were evaluated throughout a 5-wk period. Kidneys were fixed by perfusion and afferent arteriole morphology, and tubulointerstitial 3-nitrotyrosine, 4-hydroxynonenal, NOX-4 subunit of renal NADPH-oxidase, and angiotensin II were quantified. Hyperuricemia induced intrarenal oxidative stress, increased expression of NOX-4 and angiotensin II, and decreased nitric oxide bioavailability, systemic hypertension, renal vasoconstriction, and afferent arteriolopathy. Tempol treatment reversed the systemic and renal alterations induced by hyperuricemia despite equivalent hyperuricemia. Moreover, because tempol prevented the development of preglomerular damage and decreased blood pressure, glomerular pressure was maintained at normal values as well. Mild hyperuricemia induced by uricase inhibition causes intrarenal oxidative stress, which contributes to the development of the systemic hypertension and the renal abnormalities induced by increased uric acid. Scavenging of the superoxide anion in this setting attenuates the adverse effects induced by hyperuricemia.

Abstract 15326: Inactivation of Mitochondrial Deacetylase Sirt3 Induces Oxidative Stress, Promotes Vascular Hypertrophy, Increases Aortic Dissections, Exacerbates Hypertension and Mortality

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anna Dikalova ◽  
Sergey Gutor ◽  
Vasiliy Polosukhin ◽  
Sergey Dikalov
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Cardiovascular Disease ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Aortic Dissection ◽  
Vascular Dysfunction ◽  
Vascular Hypertrophy ◽  
Abdominal Aortic ◽  
Aortic Dissections

Introduction: Vascular dysfunction plays a key role in hypertension and cardiovascular disease, which causes one-third of deaths worldwide. Mitochondrial dysfunction contributes to these conditions; however, specific mechanisms are not clear. We showed inactivation of mitochondrial deacetylase Sirt3 in arterioles from patients with essential hypertension associated with superoxide dismutase inactivation, vascular inflammation and oxidative stress. Hypothesis: We hypothesized that the loss of vascular Sirt3 induces oxidative stress, promotes vascular dysfunction and hypertension. Methods: To test this hypothesis, we developed tamoxifen-inducible smooth muscle specific Sirt3 knockout mice (SmcSirt3KO) by crossing the Sirt3flox/flox mice with mice carrying a gene for inducible Cre in the vascular smooth muscle cells. Results and Discussion: Hypertension was modestly increased but considerably increased mortality in angiotensin II-infused SmcSirt3KO mice (35% vs 5% in WT) which was associated with higher rate of aortic dissections (50% vs 10% in WT). The basal superoxide and nitric oxide levels were not affected in SmcSirt3KO mice, however, angiotensin II infusion significantly increased superoxide and nitric oxide inactivation in SmcSirt3KO mice compared with wild-type mice supporting the pathological role of smooth muscle Sirt3 impairment. Post-mortem analysis showed high frequency of abdominal aortic aneurysms in angiotensin II-infused SmcSirt3KO mice suggesting that adverse vascular remodeling contributed to high mortality in these mice. To gain further insight into vascular pathology we performed histological examination using Verhoeff-van Gieson staining. Angiotensin II-infused SmcSirt3KO mice had 5-time higher abdominal aortic dissections rate, increased vascular hypertrophy, and disrupted elastic lamellae. Conclusion: Aortic dissection is a catastrophic disease with high mortality and morbidity characterized by fragmentation of elastin and smooth muscle cell dysfunction. Our data suggest that Sirt3 impairment can contribute to vascular hypertrophy, aortic dissection, end-organ-damage and mortality. It is conceivable that targeting Sirt3 may have therapeutic potential in cardiovascular disease.

Abstract 189: Toll-like Receptor 2 Blockade Decreases Contractility in Angiotensin II-induced Hypertensive Rat Resistance Arteries

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Trevor Hardigan ◽  
Maria-Alicia Sepulveda ◽  
Kenia Pedrosa Nunes ◽  
R. Clinton Webb
Keyword(s):  
Angiotensin Ii ◽  
Vascular Dysfunction ◽  
Renin Angiotensin System ◽  
Mesenteric Arteries ◽  
Sodium Balance ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Response Curves ◽  
Tlr2 Expression ◽  
The Impact

Toll-like receptors (TLRs) are pattern recognition receptors of the innate immune system that recognize endogenous damage-associated molecular patterns (DAMPS). TLR2 plays a role in cardiovascular diseases such as atherosclerosis and heart failure, but its role in hypertension is unknown. Angiotensin II (ANG), the effector molecule of the renin-angiotensin system, has been shown to cause an immune response leading to an inflammatory profile, in addition to its effects on vascular tone and sodium balance. We hypothesized that signaling through TLR2 in ANG-induced hypertension contributes to an increase in resistance artery contractility and vascular dysfunction. Sprague-Dawley rats were implanted with osmotic mini-pumps dispensing ANG (60 mg/day) for a 28 day period. Systolic blood pressure (measured directly via femoral canulation to confirm the ANG rats as a model of hypertension) was significantly increased in the ANG-treated rats (170 ±4.79 mmHg) vs. control (97 ±6.9 mmHg (p<0.05)). Concentration response curves to norepinephrine (NE; 10-9-10-4 M) were performed in second and third order mesenteric arteries from control and angiotensin-treated rats. Vessels were pre-incubated with and without antibody to TLR2 (1μg) for 35 minutes prior to the concentration-response curves to determine the impact of TLR2 blockade. The EMax (force of contraction as % of maximum KCl response) of the ANG vessels treated with anti-TLR2 was significantly lower than that of the ANG vessels alone (EMax: 129.2±10.69% vs 183.8±16.73%, respectively), and comparable to control-vessel levels (EMax in control vessels: 135.1±4.360%, p<0.05). Additionally, we sought to determine protein levels of TLR2 and downstream signaling protein MyD88 in the mesenteric arteries. In the arteries from the ANG treated animals, TLR2 expression was significantly increased 2.95±0.20 fold above control, and MyD88 expression was increased 1.35±0.06 fold above control (p<0.05). This suggests that TLR2 signaling leads to augmented contractility and is associated with the vascular dysfunction observed in hypertension.

Hesperidin Suppresses Renin-Angiotensin System Mediated NOX2 Over-Expression and Sympathoexcitation in 2K-1C Hypertensive Rats

2018 ◽  
Vol 46 (04) ◽  
pp. 751-767 ◽  
Author(s):  
Chutamas Wunpathe ◽  
Prapassorn Potue ◽  
Putcharawipa Maneesai ◽  
Sarawoot Bunbupha ◽  
Parichat Prachaney ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vascular Dysfunction ◽  
Renin Angiotensin System ◽  
Receptor Protein ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Over Expression

Hesperidin, a flavonoid derived from citrus fruits, possesses several beneficial effects including anti-oxidation and anti-inflammation. The aim of this study was to investigate the effects of hesperidin on the renin-angiotensin system (RAS) cascade that mediated oxidative stress and sympathoexcitation in two-kidney, one-clipped (2K-1C) hypertensive rats. 2K-1C hypertension was induced in male Sprague-Dawley rats. Hypertensive rats were treated with hesperidin at 20[Formula: see text]mg/kg or 40[Formula: see text]mg/kg or losartan at 10[Formula: see text]mg/kg beginning at three weeks after surgery and then continued for four weeks ([Formula: see text]/group). Hesperidin reduced blood pressure in a dose-dependent manner in hypertensive rats compared to untreated rats ([Formula: see text]). Increased plasma angiotensin converting enzyme (ACE) activity and angiotensin II levels, as well as, upregulated AT1 receptor protein expression in aortic tissues were attenuated in hypertensive rats treated with hesperidin. Hesperidin suppressed oxidative stress markers and NADPH oxidase over-expression, and restored plasma nitric oxide metabolites in 2K-1C rats. This was associated with improvement of the vascular response to acetylcholine in isolated mesenteric vascular beds and aortic rings from 2K-1C rats treated with hesperidin ([Formula: see text]). Enhancement of nerve-mediated vasoconstriction related to high plasma noradrenaline in the 2K-1C group was alleviated by hesperidin treatment ([Formula: see text]). Furthermore, losartan exhibited antihypertensive effects by suppressing the RAS cascade and oxidative stress and improved vascular dysfunction observed in 2K-1C rats ([Formula: see text]). Based on these results, it can be presumed that hesperidin is an antihypertensive agent. Its antihypertensive action might be associated with reducing RAS cascade-induced NOX2 over-expression and sympathoexcitation in 2K-1C hypertensive rats.

A Review of Angiotensin Receptor Blocker-based Therapies at all Levels of Cardiovascular Risk

2011 ◽  
Vol 7 (4) ◽  
pp. 254 ◽  
Author(s):  
Giuliano Tocci ◽  
Lorenzo Castello ◽  
Massimo Volpe ◽  
◽  
◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ventricular Hypertrophy ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Clinical Settings ◽  
Angiotensin Ii Receptor ◽  
Angiotensin System ◽  
Receptor Blockers ◽  
Artery Disease

The renin–angiotensin system (RAS) has a key role in the maintenance of cardiovascular homeostasis, and water and electrolyte metabolism in healthy subjects, as well as in several diseases including hypertension, left ventricular hypertrophy and dysfunction, coronary artery disease, renal disease and congestive heart failure. These conditions are all characterised by abnormal production and activity of angiotensin II, which represents the final effector of the RAS. Over the last few decades, accumulating evidence has demonstrated that antihypertensive therapy based on angiotensin II receptor blockers (ARBs) has a major role in the selective antagonism of the main pathological activities of angiotensin II. Significant efforts have been made to demonstrate that blocking the angiotensin II receptor type 1 (AT1) subtype receptors through ARB-based therapy results in proven benefits in different clinical settings. In this review, we discuss the main benefits of antihypertensive strategies based on ARBs in terms of their efficacy, safety and tolerability.

Renal endothelial dysfunction and impaired autoregulation after ischemia-reperfusion injury result from excess nitric oxide

2006 ◽  
Vol 291 (3) ◽  
pp. F619-F628 ◽  
Author(s):  
Zhengrong Guan ◽  
Glenda Gobé ◽  
Desley Willgoss ◽  
Zoltán H. Endre
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Endothelial Nitric Oxide

Endothelial dysfunction in ischemic acute renal failure (IARF) has been attributed to both direct endothelial injury and to altered endothelial nitric oxide synthase (eNOS) activity, with either maximal upregulation of eNOS or inhibition of eNOS by excess nitric oxide (NO) derived from iNOS. We investigated renal endothelial dysfunction in kidneys from Sprague-Dawley rats by assessing autoregulation and endothelium-dependent vasorelaxation 24 h after unilateral (U) or bilateral (B) renal artery occlusion for 30 (U30, B30) or 60 min (U60, B60) and in sham-operated controls. Although renal failure was induced in all degrees of ischemia, neither endothelial dysfunction nor altered facilitation of autoregulation by 75 pM angiotensin II was detected in U30, U60, or B30 kidneys. Baseline and angiotensin II-facilitated autoregulation were impaired, methacholine EC50 was increased, and endothelium-derived hyperpolarizing factor (EDHF) activity was preserved in B60 kidneys. Increasing angiotensin II concentration restored autoregulation and increased renal vascular resistance (RVR) in B60 kidneys; this facilitated autoregulation, and the increase in RVR was abolished by 100 μM furosemide. Autoregulation was enhanced by Nω-nitro-l-arginine methyl ester. Peri-ischemic inhibition of inducible NOS ameliorated renal failure but did not prevent endothelial dysfunction or impaired autoregulation. There was no significant structural injury to the afferent arterioles with ischemia. These results suggest that tubuloglomerular feedback is preserved in IARF but that excess NO and probably EDHF produce endothelial dysfunction and antagonize autoregulation. The threshold for injury-producing, detectable endothelial dysfunction was higher than for the loss of glomerular filtration rate. Arteriolar endothelial dysfunction after prolonged IARF is predominantly functional rather than structural.

scholarly journals Inflammatory Monocytes Determine Endothelial Nitric-oxide Synthase Uncoupling and Nitro-oxidative Stress Induced by Angiotensin II

2014 ◽  
Vol 289 (40) ◽  
pp. 27540-27550 ◽  
Author(s):  
Sabine Kossmann ◽  
Hanhan Hu ◽  
Sebastian Steven ◽  
Tanja Schönfelder ◽  
Daniela Fraccarollo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Inflammatory Monocytes ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Abstract 814: Atorvastatin Attenuates Oxidative Stress And Improves Neuronal Nitric Oxide Synthase In The Brain Stem Of Heart Failure Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Joseph Francis ◽  
Li Yu ◽  
Anuradha Guggilam ◽  
Srinivas Sriramula ◽  
Irving H Zucker
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Brain Stem ◽  
Mrna Expression ◽  
Natriuretic Peptide ◽  
Left Ventricular ◽  
Neuronal Nos ◽  
The Brain

3-Hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to reduce the incidence of myocardial infarction independent of their lipid-lowering effects. Nitric oxide (NO) in the central nervous system contributes to cardiovascular regulatory mechanisms. Imbalance between nitric oxide (NO) and superoxide anion (O 2 . − ) in the brain may contribute to enhanced sympathetic drive in heart failure (HF). This study was done to determine whether treatment with atorvastatin (ATS) ameliorates the imbalance between NO and O 2 . − production in the brain stem and contributes to improvement of left ventricular (LV) function. Methods and Results: Myocardial infarction (MI) was induced by ligation of the left coronary artery or sham surgery. Subsequently, mice were treated with ATS (10 μg/kg) (MI + ATS), or vehicle (MI + V). After 5 weeks, echocardiography revealed left ventricular dilatation in MI mice. Realtime RT-PCR indicated an increase in the mRNA expression of the LV hypertrophy markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Neuronal NOS (nNOS) and endothelial NOS (eNOS) mRNA expression were significantly reduced, while that of NAD(P)H oxidase subunit (gp91phox) expression was elevated in the brain stem of MI mice. Compared with sham-operated mice, ATS-treated mice showed reduced cardiac dilatation, decreased ANP and BNP in the LV. ATS also reduced gp91phox expression and increased nNOS mRNA expression in the brain stem, while no changes in eNOS and iNOS were observed. Conclusion: These findings suggest that ATS reduces oxidative stress and increases neuronal NOS in the brain stem, and improves left ventricular function in heart failure.

Abstract 337: Activation of Myocardial AMP-activated Protein Kinase by Metformin Prevents Progression of Heart Failure in Dogs; Involvement of eNOS Activation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hideyuki Sasaki ◽  
Hiroshi Asanuma ◽  
Masashi Fujita ◽  
Hiroyuki Takahama ◽  
Masanori Asakura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Heart Failure ◽  
Cell Death ◽  
Protein Kinase ◽  
Left Ventricular ◽  
Vehicle Group ◽  
Mrna Levels ◽  
Compound C ◽  
Amp Activated Protein Kinase

Background; Several studies have shown that metformin activates AMP-activated protein kinase (AMPK), which mediates potent cardioprotection against ischemia-reperfusion injury. AMPK is also activated in experimental failing myocardium, suggesting that activation of AMPK is beneficial for the pathophysiology of heart failure. We investigated whether metformin prevents oxidative stress-induced cell death in rat cardiomyocytes and attenuates the progression of heart failure in dogs. Methods and Results; The treatment with metformin (10 μmol/L) protected the rat cultured cardiomyocytes against cell death due to H 2 O 2 exposure (50 μmol/L) as indicated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), TUNEL staining, and flow cytometry. These effects were blunted by an AMPK inhibitor, compound-C (20 μmol/L), suggesting that the activation of AMPK decreased the extent of apoptosis-induced cell death due to H 2 O 2 exposure. Continuous rapid ventricular pacing (230/min for 4 weeks) in dogs caused heart failure and the treatment with metformin (100 mg/kg/day PO, n=8) decreased left ventricular (LV) end-diastolic dimension (32.8±0.4 vs. 36.5±1.0 mm, p< 0.01) and pressure (11.8±1.1 vs. 22±0.9 mmHg, p< 0.01), and increased LV fractional shortening (18.6±1.8 vs. 9.6±0.7 %, p< 0.01) along with enhanced phosphorylation of AMPK and the decreased the number of TUNEL-positive cells of the LV myocardium compared with the vehicle group (n=8). Interestingly, metformin increased the protein and mRNA levels of endothelial nitric oxide synthase of the LV myocardium and plasma nitric oxide levels. Metformin improved the plasma insulin resistance without increased myocardial GLUT-4 translocation. Furthermore, the subcutaneous administration of AICAR (50 mg/kg/every other day), another AMPK activator mediated the equivalent effects to metformin, strengthening the pivotal role of AMPK in reduction of apoptosis and prevention of heart failure. Conclusions; Activation of myocardial AMPK attenuated the oxidative stress-induced cardiomyocyte apoptosis and prevented the progression of heart failure in dogs, along with eNOS activation. Thus, metformin or AICAR may be applicable as a novel therapy for heart failure.

Androgens augment proximal tubule transport

2004 ◽  
Vol 287 (3) ◽  
pp. F452-F459 ◽  
Author(s):  
Albert Quan ◽  
Sumana Chakravarty ◽  
Jian-Kang Chen ◽  
Jian-Chun Chen ◽  
Samer Loleh ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Specific Binding ◽  
Extracellular Volume ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Renin Angiotensin

The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawley rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 ± 0.31 vs. 3.31 ± 0.23 nl·min−1·mm−1, P < 0.01). Luminally perfusing with either enalaprilat (10−4 M) to inhibit production of angiotensin II or losartan (10−8 M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blot analysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.

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