Angiotensin II Infusion Alters Vascular Function in Mouse Resistance Vessels: Roles of O–·2 and Endothelium

2005 ◽  
Vol 43 (1) ◽  
pp. 109-119 ◽  
Author(s):  
Dan Wang ◽  
Tina Chabrashvili ◽  
Lillian Borrego ◽  
Shakil Aslam ◽  
Jason G. Umans
Keyword(s):  
Angiotensin Ii ◽  
Vascular Function ◽  
Resistance Vessels

Abnormal vascular function and morphology in preeclampsia: a study of isolated resistance vessels

1985 ◽  
Vol 69 (4) ◽  
pp. 477-482 ◽  
Author(s):  
C. Aalkjaer ◽  
H. Danielsen ◽  
P. Johannesen ◽  
E. B. Pedersen ◽  
A. Rasmussen ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Pregnant Women ◽  
Vascular Function ◽  
Direct Evidence ◽  
The Other ◽  
Vascular Changes ◽  
Direct Information ◽  
Vascular Abnormalities ◽  
Media Thickness ◽  
Resistance Vessels

1. In order to obtain direct information about vascular changes associated with pre-eclampsia, the morphological and functional characteristics of isolated omental resistance vessels from 11 women with pre-eclampsia, 10 normotensive pregnant women and eight normotensive nonpregnant women were determined. 2. In vessels from the women with preeclampsia, the ratio of media thickness to lumen diameter was increased, compared with that in vessels from the other two groups. 3. The vessels from the women with preeclampsia had an increased responsiveness to angiotensin II and a decreased rate of relaxation, but only when compared with the vessels from the normotensive pregnant women. However, no difference in responsiveness to noradrenaline was found between any of the groups. 4. The angiotensin II responsiveness of the vessels from the women with pre-eclampsia and from the non-pregnant women were similar, suggesting that pre-eclampsia is associated with an absence of the change in vascular function which normally occurs during pregnancy. 5. The study provides direct evidence for an involvement of vascular abnormalities in the pathogenesis of pre-eclampsia.

Beneficial Morphofunctional Changes Promoted by Sildenafil in Resistance Vessels in the Angiotensin II-Induced Hypertension Model

2018 ◽  
Vol 19 (6) ◽  
pp. 483-494 ◽  
Author(s):  
Ananda T. Dias ◽  
Marcos A.S. Leal ◽  
Tadeu C. Zanardo ◽  
Gisele M. Alves ◽  
Marcella L. Porto ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Resistance Vessels ◽  
Induced Hypertension

Bradykinin has no acute effect on the response of forearm blood flow to sympathetic stimulation in man

1990 ◽  
Vol 78 (4) ◽  
pp. 399-401 ◽  
Author(s):  
M. J. Cullen ◽  
J. R. Cockcroft ◽  
D. J. Webb
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Negative Pressure ◽  
Enzyme Inhibitor ◽  
Lower Body Negative Pressure ◽  
Acute Effect ◽  
Acute Administration ◽  
Lower Body ◽  
Resistance Vessels ◽  
Sympathetic Responses

1. Six healthy male subjects received 0.9% (w/v) NaCl (saline) followed by incremental doses of bradykinin (1, 3 and 10 pmol/min), via the left brachial artery. Blood flow and the response of blood flow to lower-body negative pressure were measured in both forearms during infusion of saline and each dose of bradykinin. 2. Bradykinin produced a moderate and dose-dependent increase in blood flow in the infused, but not the non-infused, forearm. Lower-body negative pressure produced an approximately 15–20% reduction in blood flow in both forearms, and this response was unaffected by local infusion of bradykinin. 3. Bradykinin, in contrast to angiotensin II, had no acute effect on peripheral sympathetic responses to lower-body negative pressure. We conclude that, in forearm resistance vessels in man, withdrawal of angiotensin II, rather than accumulation of bradykinin, is likely to account for the attenuation of peripheral sympathetic responses after acute administration of a converting-enzyme inhibitor.

Alterations in vascular function by syncytiotrophoblast extracellular vesicles via lectin-like oxidized low-density lipoprotein receptor-1 in mouse uterine arteries

2018 ◽  
Vol 132 (21) ◽  
pp. 2369-2381 ◽  
Author(s):  
Floor Spaans ◽  
Anita Quon ◽  
Stewart R. Rowe ◽  
Jude S. Morton ◽  
Raven Kirschenman ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Extracellular Vesicles ◽  
Vascular Function ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Oxidized Low Density Lipoprotein ◽  
Uterine Arteries ◽  
Density Lipoprotein Receptor

Syncytiotrophoblast extracellular vesicles (STBEVs), released into the maternal circulation during pregnancy, have been shown to affect vascular function; however, the mechanism remains unknown. In rats, STBEVs were shown to reduce endothelium-mediated vasodilation via lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a multi-ligand scavenger receptor that has been associated with vascular dysfunction. Recently, LOX-1 was shown to interact with the angiotensin II type 1 receptor (AT-1). We hypothesized that, in pregnant mice, STBEVs would impair vascular function via LOX-1 and would specifically affect angiotensin II responses. Uterine arteries from pregnant control (C57BL/6) and LOX-1 knockout (LOX-1KO) mice were isolated on gestational day (GD) 18.5. Endothelium-dependent (methylcholine (MCh); ± N(G)-Nitro-L-arginine methyl ester to assess nitric oxide (NO) contribution), and -independent (sodium nitroprusside) vasodilation, and vasoconstriction (angiotensin II; ± AT-1 [candesartan] or angiotensin II type 2 receptor (AT-2) [PD123.319] receptor antagonists; high potassium salt solution) responses were assessed using wire myography. AT-1 and AT-2 expression was analyzed using fluorescence microscopy. Human umbilical vein endothelial cells (HUVECs) were stimulated with STBEVs ± LOX-1 blocking antibody, and superoxide and peroxynitrite production were analyzed. Although MCh-induced vasodilation was decreased (P=0.0012), NO contribution to vasodilation was greater in LOX-1KO mice (P=0.0055). STBEVs delayed angiotensin II tachyphylaxis in arteries from control but not LOX-1KO mice (P<0.0001), while AT-1 and AT-2 expression was unchanged. STBEVs increased peroxynitrite production in HUVECs via LOX-1 (P=0.0091). In summary, LOX-1 deletion altered endothelium-mediated vasodilation, suggesting that LOX-1 contributes to vascular adaptations in pregnancy. STBEVs increased angiotensin II responsiveness and oxidative stress levels via LOX-1, suggesting that increased LOX-1 expression/activation or STBEVs could adversely affect vascular function and contribute to vascular complications of pregnancy.

Abstract 066: Cyclooxygenase-depended Signaling Via Thromboxane Prostanoid Receptors Mediates Endothelin-i Induced Ros Generation In Mesenteric Resistance Vessels From Mice Infused With Angiotensin Ii

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Christopher S Wilcox ◽  
Cheng Wang ◽  
Dan Wang
Keyword(s):  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Ros Generation ◽  
Oxygen Species ◽  
Ang Ii ◽  
Wild Type ◽  
Prostanoid Receptors ◽  
Resistance Vessels ◽  
Cox 2 ◽  
Cox 1

Background: Angiotensin II (Ang II) increases reactive oxygen species (ROS) and contractions to thromboxane and endothelin-1 (ET-1). Therefore, we tested the hypothesis that cyclooxygenase (COX) and/or thromboxane-prostanoid receptors (TP-Rs) mediate enhanced ROS generations with ET-1 in Ang II-infused mice. Methods: ROS was assessed by urinary 8-isoprotane(8-Iso) excretion and ethedium : dihydroetheldium (DHE) in mesenteric resistance arterioles (MRAs) from wild type (+/+) and littermate COX-1 -/- or TP-R -/- mice infused with vehicle or angiotensin II (Ang II, 400 ng/kg/min for 14 days) (n=6/ group, mean ±SEM). Results: Ang II infusion increased excretion (ng/mg creatine) of TxB 2 (1.3±0.1±1.0±0.1 in COX-1 +/+ mice and 1.9±0.1 vs 1.2±0.1 in TP-R +/+ mice, all P<0.05) and 8-Iso (2.1±0.2 vs 1.4±0.1 in COX-1 +/+ mice and 2.2±0.1 vs 1.4±0.2 in TP-R +/+ mice, all P<0.05) but not in COX-1 -/- or TP-R -/- mice. Ang II enhanced ROS generation (Δunit) with 10 -7 M ET-1 in MRAs from both +/+ mouse genotypes (1.7±0.2 vs 0.1±0.1 in COX-1 +/+ mice and 3.2±0.3 vs 0.1±0.1 in TP-R +/+ mice, all P<0.01). However, this increase in ROS was fully prevented in TP-R-/- mouse vessels (0.3±0.2 vs 0.2±0.1, NS) and in COX-1 +/+ mouse vessels after combined blockade of COX-1( 10 -5 M SC-560) and -2 (paracoxib 10 -5 M) (0.2±0.1 vs 0.1±0.1, NS) and in COX-1 -/- mouse vessels after paracoxib (0.2±0.1 vs 0.2±0.2, NS). Increased ROS generation was only partially prevented in COX-1 -/- mouse vessels (0.5±0.1 vs 0.2±0.2, P<0.05) or in COX-1 +/+ mouse vessels after blockade of COX-1 ( 0.7±0.1 vs 0.1±0.1, NS) or COX-2 (1.0±0.1 vs 0.1±0.1,P<0.05). Conclusions: Increased ROS generation with ET-1 in microvessels from Ang II infused mice depends on products of both COX-1 and -2 that activate TP-Rs. Thus, combined blockade of COX-1 and -2 or TP-Rs may prevent vascular ROS and its many complications during increased Ang II and ET-1, such as hypertension, hypoxia or shock.

Abstract P074: Mitochondrial Isolevuglandins Contribute To Vascular Oxidative Stress And Mitochondria-targeted Scavenger Of Isolevuglandins Reduces Mitochondrial Dysfunction And Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Anna Dikalova ◽  
Vladimir Mayorov ◽  
Liang Xiao ◽  
Alexander Panov ◽  
Venkataraman Amarnath ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Mitochondrial Dysfunction ◽  
Vascular Function ◽  
Therapeutic Potential ◽  
Protein Adducts ◽  
Specific Marker ◽  
Mitochondrial Oxidative Stress ◽  
Major Health Problem ◽  
Multiple Drugs

Hypertension remains a major health problem in Western Societies, and blood pressure is poorly controlled in a third of patients despite use of multiple drugs. Mitochondrial dysfunction contributes to hypertension and mitochondria-targeted agents can potentially improve treatment of hypertension. We have proposed that mitochondrial oxidative stress produces reactive dicarbonyl lipid peroxidation products isolevuglandins (isoLGs) and that scavenging of mitochondrial isoLG improves vascular function and reduces hypertension. To test this hypothesis, we have studied the accumulation of mitochondrial isoLG-protein adducts in human patients with essential hypertension and angiotensin II mouse model of hypertension using mass spectrometry and Western blot analysis. The therapeutic potential of targeting mitochondrial isoLG was tested by the novel mitochondria-targeted isoLG scavenger, mito2HOBA. Mitochondrial isoLG in arterioles isolated from hypertensive patients were 250% greater than in arterioles from normotensive subjects, and ex vivo mito2HOBA treatment of arterioles from hypertensive subjects improved deacetylation of a key mitochondrial antioxidant, superoxide dismutase 2 (SOD2). In human aortic endothelial cells, mito2HOBA diminished mitochondrial superoxide and inhibited cardiolipin oxidation, a specific marker of mitochondrial oxidative stress. In angiotensin II-infused mice, mito2HOBA prevented accumulation of mitochondrial isoLG-protein adducts, improved Sirt3 mitochondrial deacetylase activity, reduced vascular superoxide, increased endothelial nitric oxide, improved endothelium-dependent relaxation, and attenuated hypertension. Mito2HOBA preserved mitochondrial respiration, protected ATP production, and reduced mitochondrial permeability pore opening in angiotensin II-infused mice. These data support the role of mitochondrial isoLGs in endothelial dysfunction and hypertension. We conclude that scavenging of mitochondrial isoLGs may have therapeutic potential in treatment of vascular dysfunction and hypertension.

Effect of increased potassium intake on the renin–angiotensin–aldosterone system and subcutaneous resistance arteries: a randomized crossover study

2020 ◽  
Author(s):  
Rasmus Dreier ◽  
Bahareh Abdolalizadeh ◽  
Camilla L Asferg ◽  
Lisbet R Hölmich ◽  
Niels H Buus ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Crossover Study ◽  
Vascular Function ◽  
Plasma Concentrations ◽  
Resistance Arteries ◽  
Renin Angiotensin Aldosterone System ◽  
Potassium Supplement ◽  
Renin Angiotensin ◽  
Potassium Intake ◽  
Urinary Potassium

Abstract Background Increased potassium intake lowers blood pressure (BP) in hypertensive patients. The underlying mechanism is not fully understood but must be complex because increased potassium intake elevates circulating concentrations of the BP-raising hormone aldosterone. Methods In a randomized placebo-controlled crossover study in 25 normotensive men, we investigated the effect of 4 weeks of potassium supplement (90 mmol/day) compared with 4 weeks of placebo on the renin–angiotensin–aldosterone system (RAAS), urine composition and 24-h ambulatory BP. Vascular function was also assessed through wire myograph experiments on subcutaneous resistance arteries from gluteal fat biopsies. Results Higher potassium intake increased urinary potassium excretion (144.7 ± 28.7 versus 67.5 ± 25.5 mmol/24-h; P &lt; 0.0001) and plasma concentrations of potassium (4.3 ± 0.2 versus 4.0 ± 0.2 mmol/L; P = 0.0002), renin {mean 16 [95% confidence interval (CI) 12–23] versus 11 [5–16] mIU/L; P = 0.0047}, angiotensin II [mean 10.0 (95% CI 6.2–13.0) versus 6.1 (4.0–10.0) pmol/L; P = 0.0025] and aldosterone [mean 440 (95% CI 336–521) versus 237 (173–386) pmol/L; P &lt; 0.0001]. Despite RAAS activation, systolic BP (117.6 ± 5.8 versus 118.2 ± 5.2 mmHg; P = 0.48) and diastolic BP (70.8 ± 6.2 versus 70.8 ± 6.3 mmHg; P = 0.97) were unchanged. In the wire myograph experiments, higher potassium intake did not affect endothelial function as assessed by acetylcholine [logarithmically transformed half maximal effective concentration (pEC50): 7.66 ± 0.95 versus 7.59 ± 0.85; P = 0.86] and substance P (pEC50: 8.42 ± 0.77 versus 8.41 ± 0.89; P = 0.97) or vascular smooth muscle cell reactivity as assessed by angiotensin II (pEC50: 9.01 ± 0.86 versus 9.02 ± 0.59; P = 0.93) and sodium nitroprusside (pEC50: 7.85 ± 1.07 versus 8.25 ± 1.32; P = 0.25) but attenuated the vasodilatory response of retigabine (pEC50: 7.47 ± 1.16 versus 8.14 ± 0.90; P = 0.0084), an activator of Kv7 channels. Conclusions Four weeks of increased potassium intake activates the RAAS in normotensive men without changing BP and this is not explained by improved vasodilatory responses ex vivo.

scholarly journals Rosiglitazone, a Ligand to PPARγ, Improves Blood Pressure and Vascular Function through Renin-Angiotensin System Regulation

PPAR Research ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
María Sánchez-Aguilar ◽  
Luz Ibarra-Lara ◽  
Leonardo Del Valle-Mondragón ◽  
María Esther Rubio-Ruiz ◽  
Alicia G. Aguilar-Navarro ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
In Silico ◽  
Vascular Function ◽  
Renin Angiotensin System ◽  
Dependent Manner ◽  
Insulin Sensitizer ◽  
Angiotensin System ◽  
Renin Angiotensin

Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPARγ) ligand, has been reported to act as insulin sensitizer and exert cardiovascular actions. In this work, we hypothesized that RGZ exerts a PPARγ–dependent regulation of blood pressure through modulation of angiotensin-converting enzyme (ACE)-type 2 (ACE2)/angiotensin-(1-7)/angiotensin II type-2 receptor (AT2R) axis in an experimental model of high blood pressure. We carried on experiments in normotensive (Sham) and aortic coarctation (AoCo)-induced hypertensive male Wistar rats. Both sham and AoCo rats were treated 7 days with vehicle (V), RGZ (5 mg/kg/day), or RGZ+BADGE (120 mg/kg/day) post-coarctation. We measured blood pressure and vascular reactivity on aortic rings, as well as the expression of renin-angiotensin system (RAS) proteins. We found that RGZ treatment in AoCo group decreases blood pressure values and improves vascular response to acetylcholine, both parameters dependent on PPARγ-stimulation. RGZ lowered serum angiotensin II (AngII) but increased Ang-(1-7) levels. It also decreased 8-hydroxy-2′-deoxyguanosine (8-OH-2dG), malondialdehyde (MDA), and improved the antioxidant capacity. Regarding protein expression of RAS, RGZ decreases ACE and angiotensin II type 1 receptor (AT1R) and improved ACE2, AT2R, and Mas receptor in AoCo rats. Additionally, an in silico analysis revealed that 5′UTR regions of RAS and PPARγ share motifs with a transcriptional regulatory role. We conclude that RGZ lowers blood pressure values by increasing the expression of RAS axis proteins ACE2 and AT2R, decreasing the levels of AngII and increasing levels of Ang-(1-7) in a PPARγ-dependent manner. The in silico analysis is a valuable tool to predict the interaction between PPARγ and RAS.

scholarly journals Renal autoregulation and passive pressure-flow relationships in diabetes and hypertension

2010 ◽  
Vol 299 (4) ◽  
pp. F837-F844 ◽  
Author(s):  
J. V. Hill ◽  
G. Findon ◽  
R. J. Appelhoff ◽  
Z. H. Endre
Keyword(s):  
Angiotensin Ii ◽  
Creatinine Clearance ◽  
Vascular Function ◽  
Sprague Dawley ◽  
Pressure Flow ◽  
Sd Rats ◽  
Pressure Threshold ◽  
Renal Flow ◽  
Renal Vascular

We investigated renal hemodynamics in isolated, perfused kidneys from rat models of diabetes and hypertension. Autoregulation and passive vascular responses were measured using stepped pressure ramps in the presence of angiotensin II (pEC50) or papaverine (0.1 mM), respectively. Male diabetic heterozygote m(Ren2)27 rats were compared with three male control groups: nondiabetic, normotensive Sprague-Dawley (SD) rats; nondiabetic, hypertensive heterozygote m(Ren2)27 rats; and diabetic, normotensive SD rats. Kidney function (proteinuria, creatinine clearance) was monitored before induction and at monthly intervals. Vascular function was measured in vitro in rats of induction age (6–8 wk) and at 2 and 4 mo postinduction. Renal flow correlated with age, but not diabetes or the Ren2 gene. Kidney weight-specific and body weight-specific renal flow differed between diabetic and nondiabetic rats because diabetic rats had higher kidney but lower body weights. Kidneys from all groups showed effective autoregulation in the presence of angiotensin II. The autoregulatory pressure threshold of m(Ren2)27 rats was higher, and the autoregulation pressure range was wider, compared with SD rats. When vascular smooth muscle activity was blocked with papaverine, pressure-flow responses differed between groups and with time. The m(Ren2)27 rat groups showed higher renal vascular resistance at lower pressures, suggesting greater vascular stiffness. In contrast, diabetic SD rat kidneys demonstrated reduced vessel stiffness. Flow was impaired in diabetic m(Ren2)27 rats at 4 mo, and this correlated with a decline in creatinine clearance. The results suggest that the characteristic late decline in renal filtration function in diabetes- and hypertension-related renal disease follows changes in renal vascular compliance.

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