Chronic intermittent hypobaric hypoxia provides vascular protection in the aorta of the 2-kidney, 1-clip rat model of hypertension

2018 ◽  
Vol 96 (8) ◽  
pp. 807-814
Author(s):  
Congrui Fu ◽  
Na Li ◽  
Yujia Yuan ◽  
Ri Wang ◽  
Jinting Chen ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Rat Model ◽  
Hypobaric Hypoxia ◽  
Critical Factor ◽  
Rat Aorta ◽  
Reduce Blood Pressure ◽  
Vascular Protection ◽  
Spontaneously Hypertensive ◽  
Intermittent Hypobaric Hypoxia ◽  
Endothelium Dependent Relaxation

Many studies have demonstrated that chronic intermittent hypobaric hypoxia (CIHH) can reduce blood pressure in spontaneously hypertensive rats and renovascular hypertensive (RVH) rats in which endothelial dysfunction is determined as a critical factor. However, whether CIHH can regulate vasodilation of the aorta in RVH rats remains unknown. The purpose of this study was to investigate the effect of CIHH on impaired relaxation of the aorta in the 2-kidney, 1-clip (2K1C) RVH rat model. The results showed CIHH improved the impaired endothelium-dependent relaxation in the 2K1C rat aorta. The endothelial dysfunction was prevented by the p38 antagonist SB203580, but not by the ERK1/2 antagonist PD98059 or JNK antagonist SP600125. Furthermore, the expression of p-eNOS, HIF-1α, and HIF-2α increased while that of p-p38 and BMP-4 decreased in CIHH-treated aortas from 2K1C rats. Finally, the p-eNOS expression was upregulated and the p-p38 expression was downregulated by pre-incubation of SB203580 or the BMP-4 antagonist Noggin with the aorta. CIHH ameliorated the impairment of endothelium-dependent relaxation through upregulating the expression of p-eNOS, which may be mediated by the inhibition of BMP-4/p-p38 MAPK, and upregulating the expression of HIFs in the 2K1C rat aorta.

Monoamine oxidases are novel sources of cardiovascular oxidative stress in experimental diabetes

2015 ◽  
Vol 93 (7) ◽  
pp. 555-561 ◽  
Author(s):  
Adrian Sturza ◽  
Oana M. Duicu ◽  
Adrian Vaduva ◽  
Maria D. Dănilă ◽  
Lavinia Noveanu ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Rat Model ◽  
Experimental Diabetes ◽  
Xylenol Orange ◽  
Diabetic Rat ◽  
Organ Bath ◽  
Monoamine Oxidases ◽  
Mao B ◽  
Cardiovascular Morbidity And Mortality ◽  
Endothelium Dependent Relaxation

Diabetes mellitus (DM) is widely recognized as the most severe metabolic disease associated with increased cardiovascular morbidity and mortality. The generation of reactive oxygen species (ROS) is a major event causally linked to the development of cardiovascular complications throughout the evolution of DM. Recently, monoamine oxidases (MAOs) at the outer mitochondrial membrane, with 2 isoforms, MAO-A and MAO-B, have emerged as novel sources of constant hydrogen peroxide (H2O2) production in the cardiovascular system via the oxidative deamination of biogenic amines and neurotransmitters. Whether MAOs are mediators of endothelial dysfunction in DM is unknown, and so we studied this in a streptozotocin-induced rat model of diabetes. MAO expression (mRNA and protein) was increased in both arterial samples and hearts isolated from the diabetic animals. Also, H2O2 production (ferrous oxidation – xylenol orange assay) in aortic samples was significantly increased, together with an impairment of endothelium-dependent relaxation (organ-bath studies). MAO inhibitors (clorgyline and selegiline) attenuated ROS production by 50% and partially normalized the endothelium-dependent relaxation in diseased vessels. In conclusion, MAOs, in particular the MAO-B isoform, are induced in aortas and hearts in the streptozotocin-induced diabetic rat model and contribute, via the generation of H2O2, to the endothelial dysfunction associated with experimental diabetes.

Persistence of EDHF pathway and impairment of the nitric oxide pathway after chronic mercury chloride exposure in rats: Mechanisms of endothelial dysfunction

2010 ◽  
Vol 30 (11) ◽  
pp. 1777-1784 ◽  
Author(s):  
S Omanwar ◽  
K Ravi ◽  
M Fahim
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Rat Aorta ◽  
Mercury Exposure ◽  
Mercury Chloride ◽  
Dependent Manner ◽  
Selective Loss ◽  
Dose Dependent ◽  
Endothelium Dependent Relaxation

Chronic mercury exposure impairs vascular function, leading to the depression of endothelium-dependent vasodilatation. Loss of the nitric oxide (NO) pathway has been implicated, but little is known about effects on other endothelial mediators. This study investigated the mechanisms of endothelial dysfunction in rats subjected to chronic mercury chloride exposure. The endothelium-dependent relaxation of rat aorta evoked by acetylcholine (ACh) and isoproterenol was impaired in a dose-dependent manner by chronic mercury chloride exposure. Endothelium-independent responses to sodium nitroprusside (SNP) were not affected by chronic mercury chloride exposure. In healthy vessels, ACh-induced relaxation was inhibited by L-N-nitroarginine methyl ester (L-NAME; 10–4M) and partially by glybenclamide (10–5M), indicating the involvement of NO and endothelium-derived hyperpolarizing factor (EDHF). In vessels from mercury-exposed rats, responses to ACh were insensitive to L-NAME but were significantly reduced by glybenclamide, indicating selective loss of NO-mediated relaxation. In vessels from mercury-exposed rats, responses to ACh were partially restored after treatment with the antioxidant, superoxide dismutase (SOD) and catalase, this effect was not seen when aorta from exposed group was incubated with L-NAME along with SOD and catalase indicating selective loss of NO-mediated vasodilatation and with no affect the EDHF-mediated component of relaxation. The results imply that chronic mercury exposure selectively impairs the NO pathway as a consequence of oxidative stress, while EDHF is able to maintain endothelium-dependent relaxation at a reduced level.

scholarly journals Mechanisms of Cardiovascular Protection Associated with Intermittent Hypobaric Hypoxia Exposure in a Rat Model: Role of Oxidative Stress

2018 ◽  
Vol 19 (2) ◽  
pp. 366 ◽  
Author(s):  
Miguel Aguilar ◽  
Alejandro González-Candia ◽  
Jorge Rodríguez ◽  
Catalina Carrasco-Pozo ◽  
Daniel Cañas ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Hypobaric Hypoxia ◽  
Cardiovascular Protection ◽  
Hypoxia Exposure ◽  
Intermittent Hypobaric Hypoxia

scholarly journals Association of testosterone with estrogen abolishes the beneficial effects of estrogen treatment by increasing ROS generation in aorta endothelial cells

2015 ◽  
Vol 308 (7) ◽  
pp. H723-H732 ◽  
Author(s):  
Tiago J. Costa ◽  
Graziela S. Ceravolo ◽  
Rosangela A. dos Santos ◽  
Maria Aparecida de Oliveira ◽  
Priscila X. Araújo ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Spontaneously Hypertensive Rats ◽  
Reactive Oxygen Species Generation ◽  
Oxygen Species ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Endothelium Dependent Relaxation

Testosterone has been added to hormone replacement therapy to treat sexual dysfunction in postmenopausal women. Whereas estrogen has been associated with vascular protection, the vascular effects of testosterone are contradictory and the effects of its association with estrogen are largely unknown. In this study we determined the effects of testosterone associated with conjugated equine estrogen (CEE) on vascular function using a model of hypertensive postmenopausal female: ovariectomized spontaneously hypertensive rats. Female spontaneously hypertensive rats were divided into sham-operated, ovariectomized (OVX), and OVX treated for 15 days with either CEE alone (OVX+CEE) or associated with testosterone (OVX+CEE+T). Angiotensin II (ANG II)-induced contraction was markedly increased in aortic rings from OVX compared with sham-operated rats. CEE treatment restored ANG-II responses, a beneficial effect abrogated with CEE+T. CEE treatment also increased endothelium-dependent relaxation, which was impaired in OVX rats. This effect was lost by CEE+T. Treatment of aortas with losartan (ANG-II type-1 receptor antagonist) or apocynin (NADPH-oxidase inhibitor) restored the endothelium-dependent relaxation in OVX and CEE+T, establishing an interplay between ANG-II and endothelial dysfunction in OVX and CEE+T. The benefits by CEE were associated with downregulation of NADPH-oxidase subunits mRNA expression and decreased reactive oxygen species generation. The association of testosterone with CEE impairs the benefits of estrogen on OVX-associated endothelial dysfunction and reactive oxygen species generation in rat aorta by a mechanism that involves phosphorylation of the cytosolic NADPH-oxidase subunit p47 phox.

scholarly journals Probucol Protects against Hypochlorite-induced Endothelial Dysfunction

2005 ◽  
Vol 280 (16) ◽  
pp. 15612-15618 ◽  
Author(s):  
Paul K. Witting ◽  
Ben J. Wu ◽  
Mark Raftery ◽  
Peter Southwell-Keely ◽  
Roland Stocker
Keyword(s):  
Endothelial Dysfunction ◽  
Sulfonic Acid ◽  
High Performance ◽  
Hypochlorous Acid ◽  
Rabbit Aorta ◽  
Vascular Protection ◽  
Two Phase ◽  
Butyl Phenol ◽  
Endothelium Dependent Relaxation

Atherosclerosis is associated with endothelial dysfunction and a heightened state of inflammation characterized, in part, by an increase in vascular myeloperoxidase and proteins modified by its principal oxidant, hypochlorous acid (HOCl). Here we examined whether probucol could protect against endothelial dysfunction induced by the two-electron oxidant HOCl. Hypochlorous acid eliminated endothelium-dependent relaxation of rabbit aorta, whereas endothelial function and tissue cGMP was preserved and elevated, respectively, in animals pretreated with probucol. Exogenously added probucol also protected against HOCl-induced endothelial dysfunction.In vitro, HOCl oxidized probucol in a two-phase process with rate constantsk1= 2.7 ± 0.3 × 102andk2= 0.7 ± 0.2 × 102m–1s–1that resulted in a dose- and time-dependent accumulation of probucol-derived disulfoxide, 4,4′-dithiobis(2,6-di-tert-butyl-phenol) (DTBP), DTBP-derived thiosulfonate, disulfone, and sulfonic acid, together with 3,3′,5,5′-tetra-tert-butyl-4,4′-diphenoquinone (DPQ) as determined by high performance liquid chromatography and mass spectrometry. Like HOCl, selectedone-electron oxidants converted probucol into DTBP and DPQ. Also, dietary andin vitroadded DTBP protected aortic rings from HOCl-induced endothelial dysfunction andin vitrooxidation by HOCl gave rise to the thiosulfonate, disulfone, and sulfonic acid intermediates and DPQ. However, the product profiles of thein vitrooxidation systems were different from those in aortas of rabbits receiving dietary probucol or DTBP ± HOCl treatment. Together, the results show that both probucol and DTBP react with HOCl and protect against HOCl-induced endothelial dysfunction, although direct scavenging of HOCl is unlikely to be responsible for the vascular protection by the two compounds.

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