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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic syndrome (MetS) is defined by a set of metabolic risk factors, including insulin resistance, central obesity, dyslipidemia, hyperglycemia, and hypertension for type 2 diabetes and cardiovascular disease. Although both retrospective and prospective clinical studies have revealed that MetS is associated with chronic renal disease, even with a nondiabetic cause, the cellular and molecular mechanisms in this association remain largely uncharacterized. Recently, increasing evidence suggests that peroxisome proliferator-activated receptors (PPARs), a subgroup of the nuclear hormone receptor superfamily of ligand-activated transcription factors, may play an important role in the pathogenesis of MetS. All three members of the PPAR nuclear receptor subfamily, PPARalpha, -beta/delta, and -gamma, are critical in regulating insulin sensitivity, adipogenesis, lipid metabolism, inflammation, and blood pressure. PPARs have also been implicated in many renal pathophysiological conditions, including diabetic nephropathy and glomerulosclerosis. Ligands for PPARs such as hypolipidemic PPARalpha activators, and antidiabetic thiazolidinedione PPARgamma agonists affect not only diverse aspects of MetS but also renal disease progression. Emerging data suggest that PPARs may be potential therapeutic targets for MetS and its related renal complications. This review focuses on current knowledge of the role of PPARs in MetS and discusses the potential therapeutic utility of PPAR modulators in the treatment of kidney diseases associated with MetS.
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PMID:PPARs and the kidney in metabolic syndrome. 1823 57

Arterial hypertension is a global public health problem owing to its high prevalence and association with increased risk for cerebral, cardiac and renal events. Hypertension frequently clusters with other cardiometabolic risk factors, such as dysglycemia, low levels of high-density lipoprotein cholesterol and high triglyceride levels. These, along with other factors such as central obesity, increased inflammation, endothelial dysfunction and thrombosis, are components of the metabolic syndrome. All guidelines recommend that the first-line therapy in metabolic syndrome should be based on lifestyle modification, consisting of diet and moderate exercise for at least 30 min/day. Concerning drug treatment of hypertension associated with other cardiometabolic risk factors, many results of head-to-head studies have demonstrated a reduction in new-onset Type 2 diabetes in hypertensive patients treated with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, when compared with conventional antihypertensive therapy. The explanations of the different actions of both these drugs include several mechanisms related to pancreatic insulin release and insulin sensitivity improvement. Another mechanism by which the inhibition of the renin-angiotensin system may improve insulin sensitivity is through the partial peroxisome proliferator-activated receptor-gamma agonism of telmisartan. For that reason, telmisartan has been considered by some experts to be an antihypertensive agent that is particularly useful in the treatment of hypertension associated with cardiometabolic risk factors. The impact of the promising metabolic action exhibited by telmisartan on the outcome of hypertensive patients aggregating other cardiometabolic risk factors waits for adequately randomized and powered clinical trials.
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PMID:Treatment of hypertension in individuals with the cardiometabolic syndrome: role of an angiotensin II receptor blocker, telmisartan. 1832 91

Corosolic acid (CRA), a constituent of Banaba leaves, has been reported to exert anti-hypertension, anti-hyperinsulinemia, anti-hyperglycemia, and anti-hyperlipidemia effects as well as to induce anti-inflammatory and anti-oxidative activities. The aim of this study was to investigate the inhibitory effects of CRA on the development of obesity and hepatic steatosis in KK-Ay mice, a genetically obese mouse model. Six-week-old KK-Ay mice were fed a high fat diet for 9 weeks with or without 0.023% CRA. Nine-week CRA treatment resulted in 10% lower body weight and 15% lower total fat (visceral plus subcutaneous fat) mass than in control mice. CRA treatment reduced fasting plasma levels of glucose, insulin, and triglyceride by 23%, 41%, and 22%, respectively. The improved insulin sensitivity in CRA-treated mice may be due on part to the increased plasma adiponectin and white adipose tissue (WAT) AdipoR1 levels. In addition, CRA treatment increased the expression of peroxisome proliferator-activated receptor (PPAR) alpha in liver and PPAR gamma in WAT. This is the first study to show that CRA treatment can contribute to reduced body weight and amelioration of hepatic steatosis in mice fed a high fat diet, due in part to increased expression of PPAR alpha in liver and PPAR gamma in WAT.
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PMID:Dietary corosolic acid ameliorates obesity and hepatic steatosis in KK-Ay mice. 1837 57

Cardiovascular disease (CVD) is the leading cause of death in the United States and many parts of the world. Potentially modifiable risk factors for CVD include tobacco use, physical inactivity, hypertension, elevated low-density lipoprotein cholesterol, and a cluster of interrelated metabolic risk factors. Over the last several decades, efforts to prevent or treat CVD risk factors have resulted in significantly lower rates of CVD-related mortality. However, many patients never achieve adequate control of CVD risk factors even when these factors have been identified. In addition, the growing prevalence of obesity and type 2 diabetes mellitus (DM) threatens to undermine the improvements in CVD that have been achieved. In the United States, approximately two thirds of adults are overweight or obese, and even modest excess body weight is associated with a significantly increased risk of CVD-related mortality. Lifestyle interventions to promote weight loss reduce the risk of CVD-related illness but are difficult for patients to sustain over long periods of time. The increased incidence of obesity has also contributed to significant increases in the prevalence of other important CVD risk factors, including hypertension, dyslipidemia, insulin resistance, and type 2 DM. Pharmacologic therapies are currently available to address individual CVD risk factors, and others are being evaluated, including endocannabinoid receptor antagonists, inhibitors of peroxisome proliferator-activated receptor subtypes alpha and gamma, and several agents that modulate the activity of glucagon-like peptide-1. The new agents have the potential to significantly improve several CVD risk factors with a single medication and may provide clinicians with several new strategies to reduce the long-term risk of CVD.
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PMID:Cardiovascular disease and modifiable cardiometabolic risk factors. 1845 39

The spontaneously hypertensive rat (SHR) is a model of cardiomyopathy that displays a genetic defect in cardiac fatty acid (FA) translocase/CD36, a plasma membrane long-chain FA transporter. Therapy with medium-chain FAs, which do not require CD36-facilitated transport, has been shown to improve cardiac function and hypertrophy in SHRs despite persistent hypertension. However, little is known about the underlying molecular mechanisms. The aim of this study was to document the impact of medium-chain triglyceride (MCT) therapy in SHRs on the expression level and activity of metabolic enzymes and signaling pathways. Four-week-old male SHRs were administered MCT (SHR-MCT) or long-chain triglyceride (SHR-LCT) for 16 wk. We used Wistar-Kyoto (WKY) rats as controls (WKY-MCT and WKY-LCT). The SHR-MCT group displayed improved cardiac dysfunction [as assessed by left ventricular (LV) end-diastolic pressure and the positive and negative first derivatives of LV pressure/P value], a shift in the beta-myosin heavy chain (MHC)-to-alpha-MHC ratio, and cardiac hypertrophy compared with the SHR-LCT group without an effect on blood pressure. Administration of MCT of SHRs reversed the LCT-induced reduction in the cardiac FA metabolic enzymatic activities of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and medium-chain acyl-CoA dehydrogenase (MCAD). In the SHR-MCT group, the protein expression and transcriptional regulation of myocardial peroxisome proliferator-activated receptor-alpha, which regulates the transcription of LCHAD and MCAD genes, corresponded to the changes seen in those enzymatic activities. Furthermore, MCT intake caused an inhibition of JNK activation in SHR hearts. Collectively, the observed changes in the myocardial activity of metabolic enzymes and signaling pathways may contribute to the improved cardiac dysfunction and hypertrophy in SHRs following MCT therapy.
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PMID:The benefit of medium-chain triglyceride therapy on the cardiac function of SHRs is associated with a reversal of metabolic and signaling alterations. 1845 26

Using a rat model with fructose-induced metabolic syndrome, the effect of gravinol was investigated. Male Wistar rats were fed a 65% fructose diet and administered 10 or 20 mg of gravinol/kg of body weight/day for 2 weeks. High-level fructose feeding led to hyperglycemia, hyperlipidemia, hypertri-glyceridemia, and hypertension. On the other hand, the administration of gravinol significantly lowered serum glucose and total cholesterol levels. The tail arterial blood pressure was significantly elevated with the high-fructose diet. However, rats given gravinol showed a lower blood pressure as compared with fructose-fed control rats. In addition, the triglyceride (TG) levels in serum and lipoprotein fraction were dose-dependently reduced in rats fed gravinol. The decreases of hepatic TG and total cholesterol by gravinol were responsible for the down-regulation of hepatic sterol regulatory element binding protein (SREBP)-1. However, gravinol did not affect the protein levels of hepatic peroxisome proliferator-activated receptor-alpha and SREBP-2. Moreover, gravinol administration in the fructose-fed rats markedly reduced the glycosylated protein and thiobarbituric acid-reactive substance levels in the serum and hepatic mitochondria, and it inhibited the increase of the cyclooxygenase-2 protein level as a result of the down-regulation of nuclear factor kappa B (NF-kappaB). Furthermore, the decrease of anti-apoptotic bcl-2 protein levels and the increase of pro-apoptotic bax protein levels by the high-fructose diet were reversed by gravinol. These findings suggest that fructose-induced metabolic syndrome is attenuated by gravinol administration, which is associated with the reduction of serum lipids and protection against the proinflammatory state induced by oxidative stress.
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PMID:Gravinol ameliorates high-fructose-induced metabolic syndrome through regulation of lipid metabolism and proinflammatory state in rats. 1854 Jun 12

Overweight and obesity lead to an increased risk for metabolic disorders such as impaired glucose regulation/insulin resistance, dyslipidemia, and hypertension. Several molecular drug targets with potential to prevent or treat metabolic disorders have been revealed. Interestingly, the activation of peroxisome proliferator-activated receptor (PPAR), which belongs to the nuclear receptor superfamily, has many beneficial clinical effects. PPAR directly modulates gene expression by binding to a specific ligand. All PPAR subtypes (alpha, gamma, and sigma) are involved in glucose metabolism, lipid metabolism, and energy balance. PPAR agonists play an important role in therapeutic aspects of metabolic disorders. However, undesired effects of the existing PPAR agonists have been reported. A great deal of recent research has focused on the discovery of new PPAR modulators with more beneficial effects and more safety without producing undesired side effects. Herein, we briefly review the roles of PPAR in metabolic disorders, the effects of PPAR modulators in metabolic disorders, and the technologies with which to discover new PPAR modulators.
PPAR Res 2008
PMID:Peroxisome Proliferators-Activated Receptor (PPAR) Modulators and Metabolic Disorders. 1856 91

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

Clofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR alpha) agonist, increases renal tubular cytochrome P450 4a (Cyp4a) expression thereby increasing 20-hydroxyeicosatetraenoic acid (20-HETE) production. To determine if clofibrate affects blood pressure regulation we studied mice with DOCA-salt induced hypertension in wild-type and PPAR alpha knockout mice. Wild-type mice treated with DOCA-salt had higher mean arterial pressures and higher cumulative sodium balance, but lower renal 20-HETE production than did vehicle-treated mice. Treating DOCA-salt mice with clofibrate attenuated the increase in mean arterial pressure and cumulative sodium balance while increasing 20-HETE production and renal Cyp4a expression. In contrast the PPAR alpha knockout mice treated with clofibrate and DOCA-salt showed no attenuation in the increase of blood pressure, cumulative sodium balance, renal 20-HETE production or Cyp4a protein expression. Expression of the PPAR alpha protein was greater in proximal tubules than in renal microvessels. Our results show that PPAR alpha pathway induces renal tubular 20-HETE production which affects sodium retention and blood pressure regulation in DOCA-salt-treated mice.
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PMID:Colfibrate attenuates blood pressure and sodium retention in DOCA-salt hypertension. 1859 30

Hypertriglyceridemia is observed in many metabolic diseases such as the metabolic syndrome, diabetes mellitus, or mixed dyslipidemia frequently leading to premature coronary heart disease (CHD). Additionally, several studies have shown that postprandial hypertriglyceridemia is pronounced in patients with CHD, metabolic syndrome, hypertension, and other pathologic conditions. The triglyceride-rich lipoprotein remnants accumulating in the postprandial state seem to be involved in atherogenesis and in events leading to thrombosis. Since abnormal postprandial lipemia is associated with pathologic conditions, its treatment is of clinical importance.Fibrates are of significant help in managing hypertriglyceridemia. This review summarizes the effect of fibric acid derivatives on postprandial lipemia. Fibrates decrease the production of and enhance the catabolism of triglyceride-rich lipoproteins through the activation of peroxisome proliferator-activated receptor-alpha. Results of clinical studies with fibrates have confirmed their action in decreasing postprandial triglyceride levels by increasing lipoprotein lipase activity, decreasing apolipoprotein CIII production, and by increasing fatty acid oxidation in the liver.It is concluded that fibrates are effective agents in lowering the postprandial increase in remnant lipoprotein particles and retinyl palmitate. Furthermore, fibrates can also affect the postprandial lipid profile by increasing hepatic lipase levels and in some cases, by reducing cholesterol ester transfer protein activity. The main target of fibrate therapy is to improve fasting hypertriglyceridemia, which is an essential component associated with improving postprandial lipemia. Fibrates are well tolerated by patients and adverse effects have been reported rarely after their administration.
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PMID:Therapeutic effects of fibrates in postprandial lipemia. 1869 Jul 58


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