Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study tested the hypothesis that evolution of the metabolic syndrome in obese Zucker rats (OZR) leads to impaired dilator reactivity of cerebral resistance arteries vs. responses determined in lean Zucker rats (LZR). Middle cerebral arteries (MCA) from 17-wk-old male LZR and OZR were isolated and cannulated with glass micropipettes. Vascular reactivity was assessed in response to challenge with ACh, sodium nitroprusside (SNP), reductions and elevations in Po2, 5-HT, and increased intralumenal pressure. Vessels were treated with the free radical scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol) to assess the role of superoxide production in altering reactivity, and passive vascular wall mechanics was assessed in each vessel. Vascular superoxide production was assessed in isolated arteries using fluorescence microscopy. Vessel dilation to ACh and hypoxia was impaired in OZR vs. LZR, although responses to SNP were normal. Vessel constriction to 5-HT, elevated Po2, and elevated intralumenal pressure was enhanced in OZR vs. LZR. Fluorescence microscopy demonstrated an increased superoxide production in arteries of OZR vs. LZR, correctable by incubation with tempol. Although treatment of vessels from OZR with tempol improved dilation to ACh and hypoxia, constrictor responses to 5-HT, elevated Po2, and pressure were not altered by tempol treatment. Indexes of vessel wall mechanics were comparable between groups. These results suggest that vasodilator reactivity of MCA of OZR in response to endothelium-dependent dilator stimuli is impaired vs. LZR and that this may represent a reduced bioavailability of signaling molecules due to oxidant scavenging. However, oxidative stress-independent increases in myogenic tone and constrictor reactivity may contribute to blunted dilator responses of cerebral microvessels.
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PMID:Oxidant stress and constrictor reactivity impair cerebral artery dilation in obese Zucker rats. 1551 4

This study tested the hypothesis that chronically elevated oxidant stress contributes to impaired active hyperemia in skeletal muscle of obese Zucker rats (OZR) vs. lean Zucker rats (LZR) through progressive deteriorations in microvascular structure. Twelve-week-old LZR and OZR were given 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol) in the drinking water for approximately 4 wk. Subsequently, perfusion of in situ gastrocnemius muscle was determined during incremental elevations in metabolic demand, while a contralateral skeletal muscle arteriole and the gastrocnemius muscle was removed to determine dilator reactivity, vessel wall mechanics, and microvessel density. Under control conditions, active hyperemia was impaired at all levels of metabolic demand in OZR, and this was correlated with a reduced microvessel density, increased arteriolar stiffness, and impaired dilator reactivity. Chronic tempol ingestion improved perfusion during moderate to high metabolic demand only and was associated with improved arteriolar reactivity and microvessel density; passive vessel mechanics were unaltered. Combined antioxidant therapy and nitric oxide synthase inhibition in OZR prevented much of the restored perfusion and microvessel density. In LZR, treatment with N(omega)-nitro-L-arginine methyl ester (L-NAME) hydrochloride and hydralazine (to prevent hypertension) impaired active hyperemia, dilator reactivity, and microvessel density, although arteriolar distensibility was not altered. These results suggest that with the development of the metabolic syndrome, chronic reductions in nitric oxide bioavailability, in part via the scavenging actions of oxidative free radicals, contribute to a loss of skeletal muscle microvessels, leading to impaired muscle perfusion with elevated metabolic demand.
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PMID:Reduced nitric oxide bioavailability contributes to skeletal muscle microvessel rarefaction in the metabolic syndrome. 1601 46

Diabetic nephropathy is the leading cause of renal failure in the United States. The obese Zucker rat (OZR; fa/fa) is a commonly used model of type 2 diabetes and metabolic syndrome (MetS), and of the nephropathy and renal oxidative stress commonly seen in these disorders. Heterozygous lean Zucker rats (LZRs; fa/+) are susceptible to high-fat diet (HFD)-induced obesity and MetS. The present study was designed to investigate whether 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL), a membrane-permeable radical scavenger, could alleviate the renal effects of MetS in OZR and LZR fed a HFD, which resembles the typical "Western" diet. OZR and LZR were fed a HFD (OZR-HFD and LZR-HFD) or regular diet (OZR-RD and LZR-RD) and allowed free access to drinking water or water containing 1 mmol/l TEMPOL for 10 weeks. When compared to OZR-RD animals, OZR-HFD animals exhibited significantly higher levels of total renal cortical reactive oxygen species (ROS) production, plasma lipids, insulin, C-reactive protein, blood urea nitrogen (BUN), creatinine (Cr), and urinary albumin excretion (P < 0.05); these changes were accompanied by a significant decrease in plasma high-density lipoprotein levels (P < 0.05). The mRNA expression levels of desmin, tumor necrosis factor-alpha (TNF-alpha), nuclear factor kappaB (NFkappaB), and NAD(P)H oxidase-1 (NOX-1) were significantly higher in the renal cortical tissues of OZR-HFD animals; NFkappaB p65 DNA binding activity as determined by electrophoretic mobility shift assay was also significantly higher in these animals. The same trends were noted in LZR-HFD animals. Our data demonstrate that TEMPOL may prove beneficial in treating the early stages of the nephropathy often associated with MetS.
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PMID:Diet-induced renal changes in Zucker rats are ameliorated by the superoxide dismutase mimetic TEMPOL. 1942 63