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

The obesity pandemic is closely related to hypertension and metabolic syndrome. Visceral adipose tissue plays a key role in the metabolic and cardiovascular complications of being overweight. The pathophysiological link between visceral adiposity and cardiometabolic complications focuses on insulin sensitivity, sympathetic nervous system, renin-angiotensin-aldosterone system (RAAS) and, only recently, on cardiac natriuretic peptide system (CNPS). RAAS and CNPS are endogenous antagonistic systems on sodium balance, cardiovascular system, and metabolism. The circulating RAAS is dysregulated in obese patients, and adipose tissue has a full local renin-angiotensin system that is active at local and systemic level. Adipocyte biology and metabolism are influenced by local renin-angiotensin system, with angiotensin II acting as a 'growth factor' for adipocytes. CNPS induces natriuresis and diuresis, reduces blood pressure, and, moreover, has powerful lipolytic and lipomobilizing activity in humans but not in rodents. In obesity, lower plasmatic natriuretic peptides levels with increasing BMI, waist circumference, and metabolic syndrome have been documented. Thus, reduced CNPS effects coupled with increased RAAS activity have a central role in obesity and its deadly complications. We propose herein an integrated view of the dysregulation of these two antagonistic systems in human obesity complicated with hypertension, metabolic syndrome, and increased cardiovascular risk.
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PMID:Renin-angiotensin system, natriuretic peptides, obesity, metabolic syndrome, and hypertension: an integrated view in humans. 1926 35

High blood pressure is an important constituent of the metabolic syndrome. However, the underlying mechanisms for development of hypertension in the metabolic syndrome are very complicated and remain still obscure. Visceral/central obesity, insulin resistance, sympathetic overactivity, oxidative stress, endothelial dysfunction, activated renin-angiotensin system, increased inflammatory mediators, and obstructive sleep apnea have been suggested to be possible factors to develop hypertension in the metabolic syndrome. Here, we will discuss how these factors influence on development of hypertension in the metabolic syndrome.
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PMID:The underlying mechanisms for development of hypertension in the metabolic syndrome. 1841 54

Prague hypertriglyceridemic (HTG) rats represent a suitable model of metabolic syndrome. We have established the set of F(2) hybrids derived from HTG and Lewis progenitors to investigate the relationship between respective polymorphism(s) of Igf2 gene and blood pressure (BP) or other cardiovascular phenotypes. HTG rats had elevated systolic BP and plasma triglycerides but lower plasma cholesterol compared to Lewis rats of both genders. In males, there was higher mean arterial pressure, diastolic BP and relative heart weight in HTG than in Lewis rats. The results obtained in the total population of F(2) hybrids indicated strong segregation of Igf2 genotype with plasma triglycerides. There was no segregation of Igf2 genotype with any BP component except BP changes occurring after the blockade of either renin-angiotensin system (RAS) or NO synthase. When F(2) population was analyzed according to gender, male F(2) progeny homozygous for HTG Igf2 allele had significantly higher plasma triglycerides and greater BP changes after NO synthase blockade than those homozygous for Lewis allele. On the contrary, male F(2) progeny homozygous for HTG Igf2 allele had significantly lower plasma cholesterol and smaller BP changes after RAS blockade. PCR analysis of Igf2 gene by using of microsatelite D1Mgh22 has shown polymorphism between HTG and Lewis rats. Sequence analysis of cDNA revealed insertion of 14 nucleotides in HTG gene. In conclusion, polymorphism in Igf2 gene may be responsible for differences in lipid metabolism between HTG and Lewis rats. It remains to determine how these abnormalities could be involved in BP regulation by particular vasoactive systems.
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PMID:Abnormal Igf2 gene in Prague hereditary hypertriglyceridemic rats: its relation to blood pressure and plasma lipids. 1841 99

Insulin resistance is a major pathological condition associated with obesity and metabolic syndrome. Insulin resistance and the renin-angiotensin system are intimately linked. We evaluated the role of the renin-angiotensin system in the pathogenesis of insulin resistance-associated, non-alcoholic steatohepatitis by using the angiotensin II type 1 receptor blocker olmesartan medoxomil in a diabetic rat model. The effects of olmesartan on methionine- and choline-deficient (MCD) diet-induced steatohepatitis were investigated in obese, diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and control Long-Evans Tokushima Otsuka (LETO) rats. Components of the renin-angiotensin system were up-regulated in the livers of OLETF rats, compared with LETO rats. In OLETF, but not LETO, rats, oral administration of olmesartan for 8 weeks ameliorated insulin resistance. Moreover, olmesartan suppressed MCD diet-induced hepatic steatosis and the hepatic expression of lipogenic genes (sterol regulatory element-binding protein-1c and fatty acid synthase) in OLETF, but not LETO, rats. In both OLETF and LETO rats, olmesartan inhibited hepatic oxidative stress (4-hydroxy-2-nonenal-modified protein) and expression of NADPH oxidase. Olmesartan also inhibited hepatic fibrosis, stellate cell activation, and expression of fibrogenic genes (transforming growth factor-beta, alpha 1 [I] procollagen, plasminogen activator inhibitor-1) in both OLETF and LETO rats. In conclusion, pharmacological blockade of the angiotensin II type 1 receptor slows the development of steatohepatitis in the OLETF rat model. This angiotensin II type 1 receptor blocker may exert insulin resistance-associated effects against hepatic steatosis and inflammation as well as direct effects against the generation of reactive oxygen species and fibrogenesis.
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PMID:Olmesartan ameliorates a dietary rat model of non-alcoholic steatohepatitis through its pleiotropic effects. 1850 44

Diabetes mellitus is the most common and rapidly growing cause of end-stage renal disease in developed countries. A classic hallmark of early diabetes mellitus includes activation of the renin-angiotensin system (RAS), which may lead to hypertension and renal tissue injury, but the mechanism of RAS activation is elusive. Here we identified a paracrine signaling pathway in the kidney in which high levels of glucose directly triggered the release of the prohypertensive hormone renin. The signaling cascade involved the local accumulation of succinate and activation of the kidney-specific G protein-coupled metabolic receptor, GPR91, in the glomerular endothelium as observed in rat, mouse, and rabbit kidney sections. Elements of signal transduction included endothelial Ca2+, the production of NO and prostaglandin (PGE2), and their paracrine actions on adjacent renin-producing cells. This GPR91 signaling cascade may serve to modulate kidney function and help remove metabolic waste products through renal hyperfiltration, and it could also link metabolic diseases, such as diabetes, or metabolic syndrome with RAS overactivation, systemic hypertension, and organ injury.
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PMID:Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney. 1853 68

Obesity is known to be a major aetiological factor in the development of hypertension. It also leads to dyslipidaemia and raised blood glucose. All of these are components of the metabolic syndrome. Thus, hypertension, as part of the syndrome, is often found together with these other abnormalities. Obesity raises blood pressure by a number of mechanisms, including activation of the sympathetic nervous system and the renin- angiotensin system. Apart from cardiovascular disease and diabetes, the metabolic syndrome is also associated with fatty liver disease, sleep apnoea and some malignancies. Measures to reduce obesity through lifestyle changes are therefore highly desirable, not because of reductions in blood pressure alone.
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PMID:Hypertension as part of the metabolic syndrome. 1854 89

Antihypertensive drugs that inhibit the renin-angiotensin system (RAS) have been proposed to have additional benefits beyond their classic effects on the cardiovascular system, including reducing the risk of new-onset diabetes. Whether RAS inhibitors vary in ability to protect against new-onset diabetes is, however, unknown. The angiotensin II type 1 receptor (AT(1)) blocker telmisartan has been discovered to also activate the peroxisome proliferator-activated receptor-gamma (PPARgamma), an established antidiabetic drug target. In patients with hypertension and biochemical features of the metabolic syndrome, telmisartan has had beneficial effects on lipid and glucose metabolism. As a selective modulator of PPARgamma, telmisartan does not cause the side effects of fluid retention and weight gain associated with conventional thiazolidinedione ligands of PPARgamma. These observations raise the possibility that combined AT(1) receptor blockade and selective PPARgamma modulation with molecules such as telmisartan could provide greater protection from new-onset diabetes and cardiovascular disease than drugs that target either the RAS or PPARgamma alone. The cardioprotective and antidiabetic effects of telmisartan are being assessed in two large clinical trials, the ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomised AssessmeNt Study in ACE-I iNtolerant subjects with cardiovascular Disease (TRANSCEND).
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PMID:Beyond the classic angiotensin-receptor-blocker profile. 1858 Aug 62

Obesity greatly increases risk of cardiovascular disease, metabolic syndrome, and diabetes mellitus. Most obese patients are unable to sustain appreciable weight loss; the body has a natural tendency to return to its previous weight. Although bariatric surgery is effective, it is not without risk. Until better treatments for obesity are available, management remains focused on lifestyle changes, drug therapy, and treating the metabolic complications of obesity. The main cause of metabolic dysfunction in obesity is visceral fat. Fat deposition in and around organs, skeletal muscle, and other tissues is thought to occur when subcutaneous adipose tissue stores are full. Creation of additional adipose-tissue stores is prevented by the mature adipocytes, which inhibit the differentiation of preadipocytes in a negative feedback loop. This inhibition is mediated, in part, by the renin-angiotensin system. Indeed, angiotensin II blockade has been shown to promote adipogenesis in vitro. Clinical studies are currently underway to investigate whether the angiotensin-II-receptor blocker telmisartan can stimulate adipogenesis, with the aim of diverting intramuscular fat back into adipose tissue and thereby restoring insulin sensitivity. If this effect can be demonstrated in humans, this type of agent might become the treatment of choice for obese or overweight people at risk of type 2 diabetes.
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PMID:The value of current interventions for obesity. 1858 Aug 64

The field of primary aldosteronism (PA) and aldosterone-related hypertension has undergone rapid evolution. From a relatively rare curiosity PA has become a common problem particularly in selected hypertensive populations. Patients with PA and aldosterone-related hypertension appear to be at higher cardiovascular and renal risk than comparable patients with essential hypertension probably due to the pleiotropic effects of aldosterone. Aldosterone is also linked to metabolic syndrome and diabetes. The aldosterone-to-renin ratio (ARR) has allowed the widespread screening for PA, but the exact cut-off values may vary in different population groups. All patients with hypertension and hypokalaemia, and young patients with hypertension, hypertension with an incidental adrenal mass, and severe or resistant hypertension should be screened. The use of the ARR to screen all hypertensives for PA is controversial as the test lacks specificity and many patients with false-positive tests will undergo complex and expensive testing to confirm the diagnosis. The fludrocortisone suppression test, the saline infusion test or 24-hour aldosterone excretion may be used to confirm PA in patients with a positive ARR. Adrenal venous sampling is the most reliable test to detect the presence of an aldosterone-producing adenoma, but spiral CT scan or adrenocortical scintigraphy may be useful in centres without facilities for adrenal venous sampling. Spironolactone is emerging as an important antihypertensive agent in patients with resistant hypertension and aldosterone-related hypertension. The ARR may be a useful guide to drug selection in hypertensives patients, but further research is needed to make more definitive recommendations.
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PMID:Primary aldosteronism and aldosterone-associated hypertension. 1858 13

In the present study, we assessed the levels of fasting homocysteine in patients with active Cushing's syndrome using two different assay methods. To determine a possible link between homocysteine and renin-angiotensin-aldosterone system (RAAS), nine patients with Cushing's syndrome and nine patients with metabolic syndrome were given a 1-month treatment with angiotensin II (AII) receptor blocker valsartan. Plasma homocysteine, active renin and aldosterone did not differ significantly among patients with Cushing's syndrome, patients with metabolic syndrome and controls. As expected, active renin increased significantly during valsartan treatment in patients with Cushing's syndrome as well as in patients with metabolic syndrome. Plasma homocysteine did not change after valsartan treatment, suggesting a lack of direct relationship between homocysteine and RAAS. Our data suggest that homocysteine might not serve as a reliable marker of endogenous hypercortisolism or of cardiovascular risk associated with Cushing's syndrome and metabolic syndrome.
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PMID:Homocysteine, renin and aldosterone in patients with Cushing's syndrome. 1859 7


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