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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pregnancy-related hypertension is defined by systolic blood pressure > or = 140 mmHg and/or diastolic blood pressure > or = 90 mmHg at any term. It is more appropriate to talk about "hypertensive pregnancy syndromes", for the clinical aspects can be very heterogeneous. This disease is still common and affects approximately 10 to 15% of pregnancies. It essentially involves pathological placentation. When the maternal endothelium tolerates the trophoblast, the pregnancy is normal. Two elements play pivotal roles in the genesis of preeclampsia: defective placentation around 16 weeks of gestation and abnormal maternal response to placentation. Hypertension is difficult to diagnose during pregnancy because pregnant women are very subject to white coat hypertension. Self-monitoring and ambulatory monitoring of blood pressure are especially useful in this situation. Insofar as possible, it is important to distinguish preexisting hypertension, which preceded pregnancy, simple pregnancy-related hypertension, and more complicated forms, for their management differs. Treatment to lower blood pressure is aimed solely at preventing maternal complications of hypertension; lt has no effect on the course of the pregnancy and is sometimes even harmful for fetal growth. Except in cases of preeclampsia, it is not urgent to begin such treatment during pregnancy. If required, blood pressure should be reduced very progressively to maintain placental perfusion while slowly reaching a target value between 120/80 and 140/90 mmHg. Platelet aggregation inhibitors are the only effective preventive treatment for placental ischemia. They are reserved for at-risk pregnancies after 16 weeks of gestation, at a dose of 100mg/day. Short-term risks are associated especially with the complicated forms of hypertension. In the long term, preeclampsia is a marker of cardiovascular risk, for these women are at risk of developing chronic hypertension or having a cardiovascular accident in later years. Pregnancy is currently considered a situation that can reveal the likelihood of developing the metabolic syndrome and its cardiovascular complications.
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PMID:[Pregnancy-related hypertension: a cardiovascular risk situation]. 1925 Jul 98

We wondered if Zucker obese (ZO) rats would be a good experimental model to evaluate cardiovascular complications of metabolic syndrome (MS). ZO rats were compared with both their littermate controls, Zucker lean (ZL) rats and to Wistar rats (reference strain). We designed this work:(i) to measure certain physical and biochemical characteristics of MS; (ii) to evaluate coronary and cardiac function in isolated conditions and after ischemia; and (iii) to study plasma and heart tissue oxidative stress markers. In vivo, ZO rats had higher levels of plasma glucose, cholesterol and triglycerides than their ZL littermates, but there was no difference between the groups for systolic arterial blood pressure and heart rate. In vitro, coronary endothelial function was notably impaired in ZO and ZL rats. After global ischemia, the worse ventricular recovery in ZO and ZL rats was associated with arrhythmias during reperfusion. We detected similar levels of plasma ascorbyle free radical, oxygen radical absorbance capacity and vitamin C concentrations in the three groups. Dihydroethidium staining showed higher superoxide production in the coronary vessels of ZO rats than in ZL and Wistar rats. Our results show that ZO might only correspond to early-stage cardiovascular complications associated with MS.
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PMID:Are Zucker obese rats a useful model for cardiovascular complications in metabolic syndrome? Physical, biochemical and oxidative stress considerations. 1926 71

We have recently shown that the inability of repetitive ischemia (RI) to activate p38 MAPK (p38) and Akt in metabolic syndrome [JCR:LA-cp (JCR)] rats was associated with impaired coronary collateral growth (CCG). Furthermore, Akt and p38 activation correlated with optimal O(2)(-). levels and were altered in JCR rats, and redox-sensitive p38 activation was required for CCG. Here, we determined whether the activation of Src, a possible upstream regulator, was altered in JCR rats and whether redox-dependent Src and Akt activation were required for CCG. CCG was assessed by myocardial blood flow (microspheres) and kinase activation was assessed by Western blot analysis in the normal zone and collateral-dependent zone (CZ). RI induced Src activation (approximately 3-fold) in healthy [Wistar-Kyoto (WKY)] animals but not in JCR animals. Akt inhibition decreased (approximately 50%), and Src inhibition blocked RI-induced CCG in WKY rats. Src inhibition decreased p38 and Akt activation. Myocardial oxidative stress (O(2)(-). and oxidized/reduced thiols) was measured quantitatively (X-band electron paramagnetic resonance). An antioxidant, apocynin, reduced RI-induced oxidative stress in JCR rats to levels induced by RI in WKY rats versus the reduction in WKY rats to very low levels. This resulted in a significant restoration of p38 (approximately 80%), Akt (approximately 65%), and Src (approximately 90%) activation in JCR rats but decreased the activation in WKY rats (p38: approximately 45%, Akt: approximately 65%, and Src: approximately 100%), correlating with reduced CZ flow in WKY rats (approximately 70%), but significantly restored CZ flow in JCR rats (approximately 75%). We conclude that 1) Akt and Src are required for CCG, 2) Src is a redox-sensitive upstream regulator of RI-induced p38 and Akt activation, and 3) optimal oxidative stress levels are required for RI-induced p38, Akt, and Src activation and CCG.
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PMID:Redox-sensitive Akt and Src regulate coronary collateral growth in metabolic syndrome. 1937 6

Previous study suggests that with evolution of the metabolic syndrome, patterns of arteriolar reactivity are profoundly altered and may constrain functional hyperemia. This study investigated interactions between parameters of vascular reactivity at two levels of resistance arterioles in obese Zucker rats (OZR), translating these observations into perfusion regulation for in situ skeletal muscle. Dilation of isolated and in situ resistance arterioles from OZR to acetylcholine, arachidonic acid (AA), and hypoxia (isolated arterioles only) were blunted vs. lean Zucker rats (LZR), although dilation to adenosine was intact. Increased adrenergic tone (phenylephrine) or intralumenal pressure (ILP) impaired dilation in both strains (OZR>LZR). Treatment of OZR arterioles with Tempol (superoxide dismutase mimetic) or SQ-29548 (prostaglandin H2/thromboxane A2 receptor antagonist) improved dilator reactivity under control conditions and with increased ILP, but had minimal effect with increased adrenergic tone. Arteriolar dilation to adenosine was well maintained in both strains under all conditions. For in situ cremasteric arterioles, muscle contraction-induced elevations in metabolic demand elicited arteriolar dilations and hyperemic responses that were blunted in OZR vs. LZR, although distal parallel arterioles were characterized by heterogeneous dilator and perfusion responses. alpha-Adrenoreceptor blockade improved outcomes at rest but had minimal effect with elevated metabolic demand. Treatment with Tempol or SQ-29548 had minimal impact at rest, but lessened distal arteriolar perfusion heterogeneity with increased metabolic demand. In blood-perfused gastrocnemius of OZR, perfusion was constrained primarily by adrenergic tone, while myogenic activation and endothelium-dependent dilation did not appear to contribute significantly to ischemia. These results of this novel, integrated approach suggest that adrenergic tone and metabolic dilation are robust determinants of bulk perfusion to skeletal muscle of OZR, while endothelial dysfunction may more strongly regulate perfusion distribution homogeneity via the impact of oxidant stress and AA metabolism.
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PMID:Integration of skeletal muscle resistance arteriolar reactivity for perfusion responses in the metabolic syndrome. 1938 88

Fetal or early postnatal stressors may predispose infants to develop diabetes, metabolic syndrome, or stroke. We hypothesized that postnatal stress will predispose animals to develop metabolic syndrome and impair the physiologic response to hypoxic-ischemic brain injury. We characterized the short- and long-term physiologic responses to postnatal stress by examining corticosterone (CS), glucose metabolism, and brain injury in neonatal and adult rats exposed to hypoxia-ischemia (H-I). Rat pups were divided into three levels of postnatal stress from postnatal day (P) 3 to P7. All rats underwent unilateral brain injury on either P7 or P134. We measured brain injury, growth, blood pressure, urine/plasma CS, plasma leptin, insulin, and glucose before and after H-I. Postnatal stress increased neonatal CS production, exacerbated neonatal white matter injury, and was associated with adult hyperglycemia after H-I despite increased insulin production. There were no group differences in adult weight, blood pressure, or leptin. Postnatal stress exacerbated brain injury and produced adult hyperglycemia, triggered after hypoxia exposure, consistent with the hypotheses that neonates exposed to early stress are more vulnerable to hypoxia and may be predisposed to develop metabolic syndrome in adulthood. Prolonged maternal separation produced more hyperglycemia than did brief daily handling.
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PMID:Postnatal stress produces hyperglycemia in adult rats exposed to hypoxia-ischemia. 1953 78

Allopurinol is an inhibitor of xanthine oxidoreductase (XOR) and inhibits the generation of uric acid (UA) as the final product of purine catabolism, as well as the resulting generation of superoxide (O2(-)), in humans. Elevation of the serum UA (SUA) level, referred to as hyperuricemia (HU), eventually leads to gout and allopurinol has been used for the treatment of HU and gout. Studies have revealed the role of elevated SUA levels and the associated oxidative stress (OS) in a broad spectrum of pathological conditions and it is anticipated that these findings would also expand the use of allopurinol as a therapeutic drug. This article presents a review of reports, mainly of recent studies, on the efficacy of allopurinol in various diseases and explores novel potential uses of the drug. Important novel and potential uses of great interest include metabolic syndrome (MetS) and related disorders, chronic kidney disease (CKD), nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Ischemia-reperfusion injury and mucositis, encountered as adverse effects of cancer treatment, have also been under investigation as potential targets for allopurinol.
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PMID:Allopurinol, an inhibitor of uric acid synthesis--can it be used for the treatment of metabolic syndrome and related disorders? 1958 65

Menopausal hormone therapy (HT) has shown conflicting cardiovascular endpoints, depending on the women studied. The endothelium is the main site for sex steroids cardiovascular action. To assess the influence of age, previous hormonal exposure and of metabolic syndrome (MS) on microcirculatory function, we studied 68 normotensive non-diabetic postmenopausal women, 34-70 years old, by dynamic nailfold videocapillaroscopy evaluating red blood cell velocity (RBCV) at baseline and during the reactive hyperemia response after 1 min ischemia (RBCV(max)) and time taken to reach it (TRBCV(max)). There was an inverse correlation between RBCV and RBCV(max), versus age (p=0.02 for both) and time since menopause (TSM, p=0.01 and p=0.03, respectively). Women who used oral contraceptives in the past showed higher RBCV (1.51+/-0.10 vs. 1.43+/-0.09 mm/s, p=0.01) and RBCV(max) (1.70+/-0.11 vs. 1.63+/-0.07 mm/s, p=0.03) compared to never user ones. A longer time after menopause without HT was associated to lower RBCV(max) (p=0.05). Women with MS had longer TRBCV(max) (9.85+/-1.77 vs. 8.47+/-1.71 s, p=0.02), as well as those with higher hematocrit, hemoglobin and leukocyte counts (p=0.03, p=0.01 and p=0.03, respectively) and lower HDL (p=0.03). In conclusion, in postmenopausal women of low cardiovascular risk, advanced age, longer TSM, longer time after menopause without HT and MS were associated to microcirculatory function impairment, whereas past use of oral contraceptives seemed to have a protective effect.
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PMID:Microcirculatory function in postmenopausal women: role of aging, hormonal exposure and metabolic syndrome. 1969 69

We examined the impact of metabolic syndrome (MS) on coronary stenosis progression and major cardiovascular (CV) events and investigated the mitigating effects of low-density lipoprotein (LDL) cholesterol lowering and LDL cholesterol lowering plus high-density lipoprotein (HDL) cholesterol increasing. This analysis combined individual patient data from 445 subjects who participated in 3 double-blinded, randomized, placebo-controlled trials (FATS, HATS, and AFREGS) comparing intensive lipid therapy to placebos on coronary stenosis progression by quantitative coronary angiography and on major CV events. The primary end points were change in mean proximal coronary diameter stenosis (Delta%S(prox)) over 3 years and the frequency of the predefined composite of coronary artery disease death, nonfatal myocardial infarction, stroke, and revascularization due to worsening ischemia. Patients with MS had 50% more rapid coronary stenosis progression and 64% increased CV event frequency compared to those without. More rapid coronary stenosis progression was significantly and independently associated with a 3.5-fold increased event risk (p <0.001). Combination lipid therapy significantly decreased stenosis progression by 83% (Delta%S(prox) 0.5 vs 2.9, p <0.001) in patients with MS and induced a small net regression in those without (Delta%S(prox) -0.3 vs 2.0, p <0.001). Combination therapy decreased the event rate by 54% (13% vs 28%, p = 0.03) in those with MS and by 82% (3% vs 17%, p = 0.002) without. On average, each 10% decrease in LDL cholesterol or 10% increase in HDL cholesterol was significantly associated with a 0.3 Delta%S(prox) decrease. Each 10% decrease in LDL cholesterol or 10% increase in HDL cholesterol was associated with 11% (p = 0.02) or 22% (p <0.001) event risk decrease. In conclusion, patients with MS have significantly more rapid coronary stenosis progression and a higher frequency of CV events. Greater stenosis progression rate is associated with a higher event rate. LDL cholesterol-lowering and HDL cholesterol-increasing therapies independently and significantly decrease coronary stenosis progression and decrease CV events.
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PMID:Effects of combination lipid therapy on coronary stenosis progression and clinical cardiovascular events in coronary disease patients with metabolic syndrome: a combined analysis of the Familial Atherosclerosis Treatment Study (FATS), the HDL-Atherosclerosis Treatment Study (HATS), and the Armed Forces Regression Study (AFREGS). 1993 75

Heterocyclic indazole derivatives are claimed in patent WO2008138448 as inhibitors of the serum- and glucocorticoid-inducible-kinase 1 (SGK1) and drugs for the pharmacological treatment of SGK1-related diseases, such as diabetes, obesity, metabolic syndrome, systemic and pulmonary hypertension, cardiac fibrosis, hypertrophy and insufficiency, arteriosclerosis, glomerulosclerosis, nephrosclerosis, nephritis, nephropathy, deranged electrolyte excretion, fibrosing and inflammatory disease (e.g., liver cirrhosis, lung fibrosis, rheumatism, arthrosis, Crohn s disease, chronic bronchitis, radiation fibrosis, sclerodermia, cystic fibrosis, scar formation and Alzheimer' disease), tumor growth, peptic ulcers and some disorders hitherto not conclusively shown to involve SGK1. Most of the claims are supported by the literature. SGK1 is ubiquitously expressed and its expression is stimulated by hyperglycemia, cell shrinkage, ischemia, glucocorticoids, mineralocorticoids and several inflammatory mediators including TGF-ss. SGK1 is activated by insulin and growth factors via the phosphatidylinositol-3-kinase pathway. SGK1 regulates ion channels (including ENaC, KCNE1/KCNQ1), carriers (including NCC, NHE3, SGLT1), Na(+)/K(+)-ATPase, enzymes (including glycogen-synthase-kinase-3) and transcription factors (including FOXO3a, ss-catenin, NF-kappaB). A gain-of-function SGK1 gene variant, carried by approximately 3 - 5% of Caucasians and approximately 10% of Africans, is associated with increased blood pressure, obesity and type 2 diabetes. In vitro and in vivo experiments suggested a critical role of SGK1 in renal fluid retention and hypertension, glucose-induced obesity, coagulation and increased matrix protein formation.
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PMID:Heterocyclic indazole derivatives as SGK1 inhibitors, WO2008138448. 2002 Dec 89

A high serum uric acid is common in subjects with pulmonary hypertension. The increase in serum uric acid may be a consequence of the local tissue ischemia and/or hypoxia, and it may also result from other factors independent of ischemia or hypoxia that occur in various forms of pulmonary hypertension. While classically viewed as a secondary phenomenon, recent studies suggest that hyperuricemia may also have a role in mediating the local vasoconstriction and vascular remodeling in the pulmonary vasculature. If uric acid does have a contributory role in pulmonary hypertension, we may see an increasing prevalence of pulmonary hypertension as hyperuricemia is common in subjects with obesity and metabolic syndrome. We propose studies to investigate the role of uric acid in pulmonary hypertension and to determine if lowering serum uric acid may have clinical benefit in this condition.
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PMID:Could uric acid be a modifiable risk factor in subjects with pulmonary hypertension? 2006 95


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