Disturbances in nitric oxide/cyclic guanosine monophosphate system in SHR/NDmcr-cp rats, a model of metabolic syndrome

Kagota, Satomi; Yamaguchi, Yu; Tanaka, Naoko; Kubota, Yōko; Kobayashi, Kyoko; Nejime, Namie; Nakamura, Kazuki; Kunitomo, Masaru; Shinozuka, Kazumasa

doi:10.1016/j.lfs.2005.06.029

Cited by 53 publications

(47 citation statements)

References 32 publications

(42 reference statements)

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“…From the above-mentioned results, it is very likely that sGC is a potential biological target for peroxynitrite. We have previously demonstrated that in aortas of SHR-cp, a decrease in sGC expression is accompanied by a decrease in cGMP levels (17). In the present study, unchanged PKG protein expression was also observed.…”

Section: Discussionsupporting

confidence: 81%

“…We have previously demonstrated that systemic oxidative-nitrosative stress is increased in SHR/ NDmcr-cp rats (SHR-cp), which display typical symptoms of metabolic syndrome (16), and proposed that peroxynitrite is involved in dysfunction of vasorelaxation in aortas of SHR-cp (17,18). However, it is currently unclear whether peroxynitrite is actually generated in the vascular walls per se via angiotensin II-induced NADPH-oxidase activation and contributes to dysfunction of vasodilation in SHR-cp.…”

Section: Introductionmentioning

confidence: 99%

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Chronic Production of Peroxynitrite in the Vascular Wall Impairs Vasorelaxation Function in SHR/NDmcr-cp Rats, an Animal Model of Metabolic Syndrome

et al. 2009

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Abstract. We have previously reported that peroxynitrite is involved in dysfunction of nitric oxide (NO)-mediated vasorelaxation in SHR/NDmcr-cp rats (SHR-cp), which display typical symptoms of metabolic syndrome. This study investigated whether peroxynitrite is actually generated in the vascular wall with angiotensin II-induced NADPH-oxidase activation, thus contributing to the dysfunction. In isolated mesenteric arteries of male 18-week-old SHR-cp, relaxations in response to acetylcholine and sodium nitroprusside were impaired compared with that in Wistar-Kyoto rats. This impaired relaxation was not restored by treatment with apocynin, an NADPH-oxidase inhibitor. Protein expression of endothelial NO synthase increased while that of soluble guanylyl cyclase (sGC) decreased in the artery. We observed increased production of superoxide anions and peroxynitrite from the artery and their inhibition by apocynin, and also increased contents of nitrotyrosine, a biomarker of peroxynitrite, in mesenteric arteries and angiotensin II in aortas. Long-term (8 weeks) administration of telmisartan, an angiotensin II type 1-receptor antagonist, prevented the impaired vasorelaxation, decreased sGC expression and increased nitrotyrosine content in mesenteric arteries. These findings suggest that in the vascular wall of SHR-cp, peroxynitrite is continually produced by the reaction of NO with NADPH oxidase-derived superoxide via angiotensin II and gradually denatures sGC protein, leading to vasorelaxation dysfunction.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Chronic Production of Peroxynitrite in the Vascular Wall Impairs Vasorelaxation Function in SHR/NDmcr-cp Rats, an Animal Model of Metabolic Syndrome

et al. 2009

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“…The relaxation in response to acetylcholine in the aorta of SHR / cp rats is markedly impaired compared with that in normal Wistar-Kyoto rats, as previously described (18). Figure 8 shows the acetylcholineinduced endothelium-dependent relaxation in the mesenteric artery from the control and 0.7% CoQ10 groups at the end of the experiment.…”

Section: Effect Of Coq10 On Endothelium-dependent Relaxation Of Mesensupporting

confidence: 72%

“…Inflammation and oxidative stress have been demonstrated to be associated with endothelial dysfunction in subjects with MetS (42) and animal models of disease (29,43). We have also previously reported that endothelium-dependent relaxations are impaired in the aorta of SHR / cp rats due to peroxynitrite generated in the vessel walls (18,44). We think that NADPH oxidasederived superoxide, probably produced due to stimulation of AT 1 receptors, reacts with NO to form peroxynitrite, which decreases active NO and damages endothelial cells, leading to attenuation of endotheliumdependent relaxation.…”

Section: Discussionmentioning

confidence: 69%

“…We have previously demonstrated that systemic oxidative stress and nitrative stress as well as inflammation increase with the development of MetS-like components in SHR / cp rats (19), which display abdominal obesity, hypertension, hyperglycemia, insulin-resistance, and hyperlipidemia (16,18). Several clinical studies have provided evidence that systemic oxidative stress, as measured by urinary 8-epi-prostaglandin F 2α (6) or plasma Ox-LDL (7,8), is associated with MetS.…”

Section: Discussionmentioning

confidence: 99%

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Beneficial Effect of Coenzyme Q10 on Increased Oxidative and Nitrative Stress and Inflammation and Individual Metabolic Components Developing in a Rat Model of Metabolic Syndrome

et al. 2008

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Abstract. Metabolic syndrome (MetS) is a group of cardiovascular risk factors, including visceral obesity, glucose intolerance, hypertension, and dyslipidemia. Increased oxidative and nitrative stress and inflammation and decreased endothelial function occur in an animal model of metabolic syndrome, SHR / NDmcr-cp (SHR / cp) rats. The present study investigated the effects of coenzyme Q10 (CoQ10), one of the important antioxidants, on the abnormal oxidative condition and characteristic components of metabolic syndrome in SHR / cp rats by maintaining them on a diet supplemented with 0.07% -0.7% CoQ10 for 26 weeks. We determined serum levels of oxidatively modified low-density lipoprotein (Ox-LDL) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as oxidative stress markers, 3-nitrotyrosine as a nitrative stress marker, 3-chlorotyrosine as a marker of myeloperoxidase (MPO)-catalyzed oxidation and high-sensitivity C-reactive protein (hsCRP) as an inflammatory marker. The administration of CoQ10 significantly attenuated the increase of oxidative and nitrative stress markers and inflammatory markers in a dose-dependent manner. CoQ10 prevented the elevated serum insulin levels, although it did not affect the elevated glucose level and dyslipidemia. CoQ10 also reduced elevated blood pressure, but did not affect body weight gain. In addition, CoQ10 improved endothelial dysfunction in the mesenteric arteries. These findings suggest that the antioxidant properties of CoQ10 can be effective for ameliorating cardiovascular risk in MetS.

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LGA‐newborn from patients with pregestational obesity present reduced adiponectin‐mediated vascular relaxation and endothelial dysfunction in fetoplacental arteries

Muñoz-Muñoz

Krause

Uauy

et al. 2018

Journal Cellular Physiology

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Maternal obesity is associated with large-for-gestational-age (LGA) neonates and programming of obesity-related cardiovascular disease in the offspring, however, the mechanisms that lead to the later are unclear. Presently, interpretations of NO-dependent changes in vascular function in LGA newborn from obese mothers are conflicting. Adiponectin improves endothelial function by increasing eNOS activity and NO production. We propose that LGAs from obese mothers present a diminished vascular response to adiponectin; thus, affecting eNOS and AMPK activation. Chorionic arteries, umbilical cord and primary cultures of umbilical artery endothelial cells (HUAEC) were collected at term (>38 weeks) from uncomplicated singleton pregnancies of LGA and adequate-for-gestational (AGA) newborn. Vascular reactivity of chorionic plate arteries was assessed by wire myography. mRNA expression of adiponectin receptors 1 (AdipoR1) and AdipoR2 in HUAEC was determined by qPCR. Protein expression of AdipoR1, AdipoR2, AMPK, phospho-AMPKα , eNOS, and phospho-eNOS after stimulation with AdipoRon was determined by Western Blot. Maximal adiponectin-induced chorionic artery relaxation in LGAs was diminished compared to control. In vitro studies showed no differences in expression of AdipoRs, total AMPK and, eNOS activation between groups; however, higher expression of total eNOS and AMPK activation in HUAEC of LGA relative to AGAs were observed. LGA HUAEC showed diminished NO production and eNOS activity compared to AGA in response to AdipoRon but no changes in AMPK activation. Placental endothelium of LGAs shows a diminished vascular response to adiponectin. Moreover, eNOS activation and adiponectin-dependent NO production is lower in HUAEC of LGA from obese mothers, indicating they present dysfuncional placental-endothelial responses.

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Disturbances in nitric oxide/cyclic guanosine monophosphate system in SHR/NDmcr-cp rats, a model of metabolic syndrome

Cited by 53 publications

References 32 publications

Chronic Production of Peroxynitrite in the Vascular Wall Impairs Vasorelaxation Function in SHR/NDmcr-cp Rats, an Animal Model of Metabolic Syndrome

Chronic Production of Peroxynitrite in the Vascular Wall Impairs Vasorelaxation Function in SHR/NDmcr-cp Rats, an Animal Model of Metabolic Syndrome

Beneficial Effect of Coenzyme Q10 on Increased Oxidative and Nitrative Stress and Inflammation and Individual Metabolic Components Developing in a Rat Model of Metabolic Syndrome

LGA‐newborn from patients with pregestational obesity present reduced adiponectin‐mediated vascular relaxation and endothelial dysfunction in fetoplacental arteries

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