Role of angiotensin II in endothelial dysfunction induced by lipopolysaccharide in mice

2007 ◽  
Vol 293 (6) ◽  
pp. H3726-H3731 ◽  
Author(s):  
Donald D. Lund ◽  
Robert M. Brooks ◽  
Frank M. Faraci ◽  
Donald D. Heistad
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Disease States ◽  
Vasomotor Function

Endotoxin [or lipopolysaccharide (LPS)] increases levels of superoxide in blood vessels and impairs vasomotor function. Angiotensin II plays an important role in the generation of superoxide in several disease states, including hypertension and heart failure. The goal of this study was to determine whether the activation of the renin-angiotensin system contributes to oxidative stress and endothelial dysfunction after endotoxin. We examined the effects of enalapril (an angiotensin-converting enzyme inhibitor) or L-158809 (an angiotensin receptor blocker) on increases of superoxide and vasomotor dysfunction in mice treated with LPS. C57BL/6 mice were treated with either enalapril (60 mg·kg−1·day−1) or L-158809 (30 mg·kg−1·day−1) for 4 days. After the third day, LPS (10–20 mg/kg) or vehicle was injected intraperitoneally, and one day later, vasomotor function of the aorta was examined in vitro. After precontraction with PGF2α, the maximal responses to sodium nitroprusside were similar in the aorta from normal and LPS-treated mice. In contrast, the relaxation to acetylcholine was impaired after LPS (54 ± 5% at 10−5, mean ± SE) compared with vessels treated with vehicle (88 ± 1%; P < 0.05). Enalapril improved ( P < 0.05) relaxation in response to acetylcholine to 81 ± 6% after LPS. L-158809 also improved relaxation in response to acetylcholine to 77 ± 4% after LPS. Superoxide (measured with lucigenin and hydroethidine) was increased ( P < 0.05) in aorta after LPS, and levels were reduced ( P < 0.05) following enalapril and L-158809. Thus, after LPS, enalapril and L-158809 reduce superoxide levels and improve relaxation to acetylcholine in the aorta. The findings suggest that activation of the renin-angiotensin system contributes importantly to oxidative stress and endothelial dysfunction after endotoxin.

scholarly journals Combination of β Adrenergic Receptor Block and Renin–Angiotensin System Inhibition Diminished the Angiotensin II-Induced Vasoconstriction and Increased Bradykinin-Induced Vasodilation in Hypertension

Dose-Response ◽  
2017 ◽  
Vol 15 (4) ◽  
pp. 155932581773793 ◽  
Author(s):  
Diego Lezama-Martínez ◽  
Ignacio Valencia-Hernández ◽  
Jazmin Flores-Monroy ◽  
Luisa Martínez-Aguilar
Keyword(s):  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Enzyme Inhibitor ◽  
Spontaneously Hypertensive Rat ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Renin Angiotensin System ◽  
Response Curves ◽  
Angiotensin System ◽  
Renin Angiotensin

In hypertension, the combination therapy is frequently used to obtain a better therapeutic effect and reduce adverse effects. One effective combination is with inhibitors and β-blockers of renin–angiotensin system. Although the mechanisms of action of each drug are already known, the antihypertensive mechanism is more complex and therefore the combined treatment mechanism is unclear. Specifically, the effect of the treatments of angiotensin-converting enzyme inhibitor or AT1 receptor antagonist with β-blocker on the angiotensin II and bradykinin reactivity has not been studied. For this reason, we evaluated the interaction between propranolol and captopril or losartan on vascular reactivity to bradykinin and angiotensin II in spontaneously hypertensive rat. We constructed concentration–response curves to angiotensin II and bradykinin after treatment of SHR with propranolol–captopril or propranolol–losartan by using rat aortic rings. While losartan or captopril with propranolol potentiated bradykinin-induced vasodilation effect, the propranolol–losartan interaction decreased the angiotensin II-induced vasoconstriction. In addition, the combinations did not reduce the heart rate significantly. These results suggest that the combined therapy decreased blood pressure to normotensive values and showed less effect for angiotensin II and greater effect for bradykinin than monotherapy which could contribute in the antihypertensive effect.

scholarly journals Recombinant Expression and Characterization of Human and Murine ACE2: Species-Specific Activation of the Alternative Renin-Angiotensin-System

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Marko Poglitsch ◽  
Oliver Domenig ◽  
Cornelia Schwager ◽  
Stefan Stranner ◽  
Bernhard Peball ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Recombinant Expression ◽  
Renin Angiotensin System ◽  
Functional Connection ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Mas Receptor ◽  
Conversion Rates ◽  
Species Specific

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase of the renin-angiotensin-system (RAS) which is known to cleave several substrates among vasoactive peptides. Its preferred substrate is Angiotensin II, which is tightly involved in the regulation of important physiological functions including fluid homeostasis and blood pressure. Ang 1–7, the main enzymatic product of ACE2, became increasingly important in the literature in recent years, as it was reported to counteract hypertensive and fibrotic actions of Angiotensin II via the MAS receptor. The functional connection of ACE2, Ang 1–7, and the MAS receptor is also referred to as the alternative axis of the RAS. In the present paper, we describe the recombinant expression and purification of human and murine ACE2 (rhACE2 and rmACE2). Furthermore, we determined the conversion rates of rhACE2 and rmACE2 for different natural peptide substrates in plasma samples and discovered species-specific differences in substrate specificities, probably leading to functional differences in the alternative axis of the RAS. In particular, conversion rates of Ang 1–10 to Ang 1–9 were found to be substantially different when applying rhACE2 or rmACE2in vitro. In contrast to rhACE2, rm ACE2 is substantially less potent in transformation of Ang 1–10 to Ang 1–9.

Endogenous renin-angiotensin system and drinking behavior in flounder

1985 ◽  
Vol 248 (2) ◽  
pp. R157-R160 ◽  
Author(s):  
R. J. Balment ◽  
S. Carrick
Keyword(s):  
Angiotensin Ii ◽  
Enzyme Inhibitor ◽  
Drinking Behavior ◽  
Renin Angiotensin System ◽  
Simultaneous Administration ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Physiological Importance ◽  
Plasma Chloride

High rates of drinking in seawater-adapted, compared with freshwater (FW)-adapted, flounder were associated with raised plasma chloride and osmotic concentrations. Hypotension in FW-adapted fish, after papaverine administration, gave rise to greatly elevated rates of drinking. This dipsogenic response apparently relied on activation of the endogenous renin-angiotensin system (RAS) and was abolished by simultaneous administration of the converting enzyme inhibitor, captopril. Exogenous angiotensin II was shown to be dipsogenic and vasopressor in the FW-adapted fish. The physiological importance of the activation of the RAS in the control of drinking behavior in euryhaline fish is discussed.

Effect of digoxin on the in vitro secretion of renin and angiotensin II/III immunoreactivity by the human adrenal gland

1992 ◽  
Vol 127 (3) ◽  
pp. 210-214 ◽  
Author(s):  
Matteo Pistorello ◽  
Margherita Cimolato ◽  
Francesco Pedini ◽  
Donatella Piovan ◽  
Marco Boscaro ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Adrenal Gland ◽  
Renin Angiotensin System ◽  
Aldosterone Secretion ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Superfusion System ◽  
Sustained Reduction ◽  
High Doses

Cardiac glycosides in man inhibit renin secretion, probably through a direct effect at the renal level (i.e. inhibition of juxtaglomerular cell Na/K ATPase). Since there is evidence that the human adrenal possesses an intrinsic renin-angiotensin system, we investigated the effect of digoxin on the in vitro generation of renin and angiotensin II/III, as well as of aldosterone, by the human adrenal gland. Minced normal adrenal tissues were studied in a superfusion system, measuring in the 15-min superfusate fractions active renin by immunoradiometric assay and angiotensin II/III and aldosterone by radioimmunoassay, respectively. In a first set of four experiments using different concentrations of digoxin in sequence for 45 min periods, digoxin 10−5, but not 10−8 and 10−6 mol/l, significantly reduced renin and angiotensin II/III output from adrenals, while no change in aldosterone was observed. In a second set of three experiments, the addition of digoxin 10−5 mol/l for 120 min caused a sustained reduction of renin and angiotensin II/III, but not of aldosterone. In the final experiment, the decrease of renin and angiotensin II/III during superfusion with digoxin 10−5 mol/l was significantly greater than that observed during superfusion with digoxin in the presence of antidigoxin antibodies. Our data indicate that digoxin at high doses reduces renin and angiotensin II/III but not aldosterone secretion by the human adrenal gland. This suggests two different effects of digoxin, probably both mediated by inhibition of the Na/K ATPase activity, on the adrenal renin-angiotensin- and aldosterone-secreting cells.

scholarly journals Inhibition of Renin-Angiotensin System Reverses Endothelial Dysfunction and Oxidative Stress in Estrogen Deficient Rats

PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e17437 ◽  
Author(s):  
Lai Ming Yung ◽  
Wing Tak Wong ◽  
Xiao Yu Tian ◽  
Fung Ping Leung ◽  
Lai Hang Yung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
And Oxidative Stress

scholarly journals Benzbromarone Attenuates Oxidative Stress in Angiotensin II- and Salt-Induced Hypertensive Model Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Nanako Muraya ◽  
Daisuke Kadowaki ◽  
Shigeyuki Miyamura ◽  
Kenichiro Kitamura ◽  
Kohei Uchimura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Radical Scavenging ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Scavenging Effect ◽  
Stress Markers ◽  
Radical Scavenging Effect

Oxidative stress induced by hyperuricemia is closely associated with the renin-angiotensin system, as well as the onset and progression of cardiovascular disease (CVD) and chronic kidney disease (CKD). It is therefore important to reduce oxidative stress to treat hyperuricemia. We previously found that benzbromarone, a uricosuric agent, has a direct free radical scavenging effect in vitro. The antioxidant effects of benzbromarone were evaluated in vivo via oral administration of benzbromarone for 4 weeks to model rats with angiotensin II- and salt-induced hypertension. Benzbromarone did not alter plasma uric acid levels or blood pressure but significantly reduced the levels of advanced oxidation protein products, which are oxidative stress markers. Furthermore, dihydroethidium staining of the kidney revealed a reduction in oxidative stress after benzbromarone administration. These results suggest that benzbromarone has a direct antioxidant effect in vivo and great potential to prevent CVD and CKD.

scholarly journals Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD

2021 ◽  
Vol 22 (13) ◽  
pp. 6702
Author(s):  
Anastasia V. Poznyak ◽  
Dwaipayan Bharadwaj ◽  
Gauri Prasad ◽  
Andrey V. Grechko ◽  
Margarita A. Sazonova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Vascular Function ◽  
Treatment Options ◽  
Renin Angiotensin System ◽  
Inflammatory Cells ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Important Player ◽  
Atherosclerosis Treatment

Atherosclerosis has complex pathogenesis, which involves at least three serious aspects: inflammation, lipid metabolism alterations, and endothelial injury. There are no effective treatment options, as well as preventive measures for atherosclerosis. However, this disease has various severe complications, the most severe of which is cardiovascular disease (CVD). It is important to note, that CVD is among the leading causes of death worldwide. The renin–angiotensin–aldosterone system (RAAS) is an important part of inflammatory response regulation. This system contributes to the recruitment of inflammatory cells to the injured site and stimulates the production of various cytokines, such as IL-6, TNF-a, and COX-2. There is also an association between RAAS and oxidative stress, which is also an important player in atherogenesis. Angiotensin-II induces plaque formation at early stages, and this is one of the most crucial impacts on atherogenesis from the RAAS. Importantly, while stimulating the production of ROS, Angiotensin-II at the same time decreases the generation of NO. The endothelium is known as a major contributor to vascular function. Oxidative stress is the main trigger of endothelial dysfunction, and, once again, links RAAS to the pathogenesis of atherosclerosis. All these implications of RAAS in atherogenesis lead to an explicable conclusion that elements of RAAS can be promising targets for atherosclerosis treatment. In this review, we also summarize the data on treatment approaches involving cytokine targeting in CVD, which can contribute to a better understanding of atherogenesis and even its prevention.

scholarly journals Effects of Resveratrol on the Renin-Angiotensin System in the Aging Kidney

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1741 ◽  
Author(s):  
In-Ae Jang ◽  
Eun Kim ◽  
Ji Lim ◽  
Min Kim ◽  
Tae Ban ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Renin Angiotensin System ◽  
Organ Damage ◽  
Protective Effects ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Endothelial Nitric Oxide

The renin-angiotensin system (RAS), especially the angiotensin II (Ang II)/angiotensin II type 1 receptor (AT1R) axis, plays an important role in the aging process of the kidney, through increased tissue reactive oxygen species production and progressively increased oxidative stress. In contrast, the angiotensin 1-7 (Ang 1-7)/Mas receptor (MasR) axis, which counteracts the effects of Ang II, is protective for end-organ damage. To evaluate the ability of resveratrol (RSV) to modulate the RAS in aging kidneys, eighteen-month-old male C57BL/6 mice were divided into two groups that received either normal mouse chow or chow containing resveratrol, for six months. Renal expressions of RAS components, as well as pro- and antioxidant enzymes, were measured and mouse kidneys were isolated for histopathology. Resveratrol-treated mice demonstrated better renal function and reduced albuminuria, with improved renal histologic findings. Resveratrol suppressed the Ang II/AT1R axis and enhanced the AT2R/Ang 1-7/MasR axis. Additionally, the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, 8-hydroxy-2′-deoxyguanosine, 3-nitrotyrosine, collagen IV, and fibronectin was decreased, while the expression of endothelial nitric oxide synthase and superoxide dismutase 2 was increased by resveratrol treatment. These findings demonstrate that resveratrol exerts protective effects on aging kidneys by reducing oxidative stress, inflammation, and fibrosis, through Ang II suppression and MasR activation.

Presence of cellular renin-angiotensin system in chromaffin cells of bovine adrenal medulla

2002 ◽  
Vol 283 (5) ◽  
pp. H1811-H1818 ◽  
Author(s):  
Jun Ming Wang ◽  
Dirk Slembrouck ◽  
Junhui Tan ◽  
Lut Arckens ◽  
Frans H. H. Leenen ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Bovine Chromaffin Cells

The presence of a local renin-angiotensin system has been established in organs that serve as angiotensin targets. In this study, the expression of angiotensinogen mRNA and subcellular localization of renin, angiotensin-converting enzyme, and angiotensin II were investigated in bovine adrenal medullary cells in primary culture. By light microscopy, expression of angiotensinogen mRNA, immunoreactive renin, angiotensin-converting enzyme, and angiotensin II were readily detectable only in the chromaffin cells. The density distribution of renin and angiotensin II in sucrose gradients suggested a concentration in chromaffin granules, a localization directly confirmed by immunoelectron microscopy. Reverse transcriptase-polymerase chain reaction and sequencing confirmed the expression of angiotensinogen in bovine chromaffin cells and the adrenal medulla. In addition, in vitro autoradiography indicated that both angiotensin-converting enzyme and angiotensin type 1 receptors were present in the adrenal medulla. These results provide the first direct evidence that chromaffin cells in the adrenal medulla are not only the target for angiotensin but should also be considered as potential local angiotensin-generating and -storing cells.

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