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

Although thiazolidinediones and magnesium supplementation improves insulin action and increases HDL-cholesterol, the potential link between serum magnesium and thiazolidinediones has received little attention. Focusing on the increase of serum magnesium, 63 eligible subjects were enrolled and randomly allocated to receive either 30 mg Pioglitazone once daily (Group A) or lifestyle intervention (Group B) during 12 weeks. Subjects were eligible if they were glucose-intolerant, and excluded if they had high blood pressure, diabetes or abnormal liver function tests. The personnel assessing outcomes were blinded to group assignment. Of the 63 eligible subjects, 3 dropped out (one in group A, and two in Group B) because they moved out of the city. So, 30 subjects in each group, who satisfactorily completed the follow-up, were included in the analysis of data. There were no serious adverse events or side effects due to Pioglitazone or lifestyle intervention. At baseline, the groups did not differ significantly in serum magnesium levels 1.73 +/- 0.17 versus 1.72 +/- 0.14 mg/dl, p = 0.80. Subjects who received Pioglitazone significantly increased their serum magnesium to 1.93 +/- 0.16 mg/dl whereas in the lifestyle intervention group the increase was 1.74 +/- 0.25 mg/dl, p < 0.0001. What this study showed was a significant increase in the serum magnesium levels of glucose-intolerant subjects who received 30 mg Pioglitazone once daily.
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PMID:Pioglitazone increases serum magnesium levels in glucose-intolerant subjects. A randomized, controlled trial. 1274 60

The objective of this study was to determine the effect of pioglitazone on blood pressure (BP) and oxidative balance in obese, hypertensive, Sprague-Dawley rats and to identify some of the molecular mechanisms involved. After 12 weeks of a moderately high-fat diet, rats diverged into obesity-prone (OP) and obesity-resistant (OR) groups (n=6 per group). At the end of the diet, peroxisome proliferator activated receptor-gamma (PPARgamma) mRNA expression and activity in the renal cortex and medulla of OP rats were significantly lower compared with that in OR rats. Pioglitazone treatment increased PPARgamma expression and activity in OP rats, suggesting a possible direct ligand-related effect of pioglitazone. As opposed to the untreated OP group, which showed moderate hypertension (systolic BP=159+/-5.3 mm Hg) after 12 weeks, pioglitazone-treated rats were normotensive (systolic BP=123.9+/-2.7 mm Hg). Insulin production was reduced by 2-fold in the OP group treated with pioglitazone. Urinary isoprostanes and renal lipid peroxides were also reduced in OP rats treated with pioglitazone compared with untreated counterparts. Also, expression of p47phox and gp91phox, both increased in OP versus OR rats, was reduced in the former by pioglitazone treatment. In addition, pioglitazone treatment increased nitrate/nitrite excretion and expression of renal endothelial and neuronal nitric oxide synthase. Collectively, the results show that pioglitazone treatment prevented hypertension and renal oxidative stress both by reducing free-radical production and by increasing nitric oxide production/availability.
Hypertension 2004 Jan
PMID:Pioglitazone prevents hypertension and reduces oxidative stress in diet-induced obesity. 1463 18

HIV-associated lipodystrophy syndrome is a syndrome occurring in HIV-infected patients who were treated with highly-active antiretroviral therapy (HAART), especially regimen containing protease inhibitors. The syndrome consists of fat redistribution, with loss of subcutaneous fat and increase in visceral fat, and metabolic disturbances, including glucose intolerance or overt diabetes and dyslipidemia. No standard treatment has been established for this syndrome. Pioglitazone is an oral antidiabetic agent that acts primarily on adipose tissue to reduce insulin resistance. The authors report a 50-year old HIV-infected woman who developed HIV-associated lipodystrophy syndrome after 3 months of HAART. She had significant weight loss with obvious loss of subcutaneous fat, together with development of hypertension, diabetes and dyslipidemia. After treatment with 30 milligrams of pioglitazone daily, her body weight increased within the first month of treatment. Subcutaneous fat loss was restored. Improvement in glycemic and lipid control was also noted. CT scan of the abdomen revealed that fatty infiltration in the liver was markedly decreased. Visceral fat as assessed by CT scan had also decreased. Pioglitazone appeared to have beneficial effects in this patient.
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PMID:Improvement of fat redistribution, insulin resistance and hepatic fatty infiltration in HIV-associated lipodystrophy syndrome by pioglitazone: a case report. 1506

The present study investigates the effect of pioglitazone treatment on blood pressure, vascular reactivity and antioxidant enzymes in L-NAME induced hypertension in normal and STZ-diabetic rats. Diabetes was induced in male Sprague Dawley rats (200+/-15 g) by single intravenous injection of 55 mg/kg of streptozotocin (STZ). Rats were randomized into diabetic and nondiabetic groups, Nomega-nitro-L-arginine-methyl ester (L-NAME, 50 mg/kg) was administered in drinking water for 4 weeks. They were treated with pioglitazone (10 mg/kg/day, p.o.) for 4 weeks and following protocol was carried out. Blood pressure, blood glucose levels and body weight were measured. Thoracic aorta was isolated and dose response curve of phenylephrine (PE) with intact and denuded endothelium was recorded. Dose response curve of acetylcholine (Ach) and sodium nitroprusside (SNP) was recorded in precontracted rings. Lipid peroxidation, superoxide dismutase, catalase, and reduced glutathione were estimated in liver, kidney, and aorta. Pioglitazone produced no significant effect on blood glucose levels, body weight and blood pressure of L-NAME administered nondiabetic and diabetic rats. Pioglitazone treatment had no significant effect on PE induced contraction and Ach induced relaxation in L-NAME diabetic and nondiabetic rats. SNP completely relaxed aortic rings of all the groups. Higher oxidative stress in case of diabetic rats was significantly (p<0.05) reduced by pioglitazone treatment. Although pioglitazone reduced oxidative stress in diabetic rats, there was no significant effect on blood pressure as there was complete absence of nitric oxide due to administration of L-NAME. Hence from the present study it can be concluded that reduction in blood pressure in case of STZ-diabetic rats is nitric oxide mediated.
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PMID:Effect of pioglitazone on L-NAME induced hypertension in diabetic rats. 1616 16

Atherogenic dyslipidemia is one of the major components of the metabolic syndrome, a complex cluster of several risk factors within a single patient that according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel III includes at least 3 of the following: large waist circumference, elevated triglyceride levels, low levels of high-density lipoprotein cholesterol (HDL-C), hypertension, and elevated fasting glucose levels, which are directly related to the incidence of coronary heart disease. Atherogenic dyslipidemia clinically presents as elevated serum triglyceride levels, increased levels of small dense low-density lipoprotein (sdLDL) particles, and decreased levels of HDL-C. An important component of atherogenic dyslipidemia is central obesity, which is defined as increased waist circumference and has recently been identified as a chief predictor of the metabolic syndrome in certain patients. Another recent study found that both body mass index and waist circumference were highly predictive of eventual development of the metabolic syndrome. Because atherogenic dyslipidemia usually precedes the clinical manifestation of the metabolic syndrome, strategies to treat it are the focus of pharmacologic intervention. For example, the 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors, commonly known as statins, benefit hypercholesterolemic patients who have atherogenic dyslipidemia that is associated with the metabolic syndrome. Pioglitazone, an antidiabetic agent that acts primarily by decreasing insulin resistance, improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Pioglitazone improves glycemic control while reducing circulating insulin levels. The investigational agent, rimonabant--a centrally and peripherally acting, selective cannabinoid type-1 receptor blocker--is the first therapy developed for managing several cardiovascular risk factors at one time. Rimonabant has shown promise in attacking atherogenic dyslipidemia from several vantage points by affecting glucose, HDL-C, triglycerides, and waist circumference in patients who are prone to atherogenic dyslipidemia.
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PMID:The metabolic basis of atherogenic dyslipidemia. 1647 58

Ragaglitazar is a novel and potent dual peroxisome proliferators activated receptor (PPAR) alpha and gamma activator. The aim of this study is to investigate the effect of ragaglitazar on blood pressure and endothelial function in insulin resistant animal model and non-insulin resistant hypertensive models. The effects ragaglitazar were tested in Zucker fa/fa, spontaneously hypertensive rats (SHR), 2 kidney 1clip rat (2K1C) and Wistar Kyoto rats (WKY). Pioglitazone was taken as a comparative standard. Ragaglitazar showed significant reduction (P<0.001) of systolic blood pressure (SBP) in insulin resistant fa/fa rats, with concomitant reduction in plasma triglycerides (TG) and insulin levels while pioglitazone (10 mg kg(-1)) showed significant (P<0.05) but comparatively less reduction. Ragaglitazar in contrast to pioglitazone showed significant reduction (P<0.05) of SBP in SHR, 2K1C while the same dose did not have any effect on normotensive WKY. Ragaglitazar also showed significant improvement in acetylcholine-induced relaxation in isolated aorta of Zucker fa/fa, SHR, 2K1C and also potentiated the insulin-induced vasorelaxation in Zucker fa/fa rats. These findings summarize that ragaglitazar shows significant reduction of BP and improvement in endothelial function not only in insulin resistant but also in non-insulin resistant hypertensive models where standard thiazolidinediones are ineffective. These data indicates that dual PPARalpha and gamma activator ragaglitazar can be beneficial for the treatment of hypertension and vascular disease commonly associated with type 2 diabetes.
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PMID:Antihypertensive effect of ragaglitazar: a novel PPARalpha and gamma dual activator. 1665 Oct 4

Peroxisome Proliferator-Activate Receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. The three PPARs (alpha, beta/delta, and gamma) are distributed differently in the different organs. PPARalpha is most common in the liver, but also found in kidney, gut, skeletal muscle and adipose tissue, while PPARbeta/delta, is fairly ubiquitous; it may be found in body tissues and brain (for myelination process and lipid metabolism in the brain). PPARgamma has 3 isoforms, such as PPARgamma 1, PPARgamma 2, and PPARgamma 3. The syndrome-X was firstly coined by Reaven in 1988 and then to be provided in 1999 by the name : the metabolic syndrome-X. This metabolic syndrome represents a "Cluster" of metabolic disorders and cardiovascular risk factors which has been collected and summarized by the author and such a cluster includes: insulin resistance/hyperinsulinemia, central obesity, glucose intolerance/DM, atherogenic dyslipidemia (increase TG, decrease HDL-cholesterol, increase Apo-B, increase small dense LDL), hypertension, prothrombotic state (increase PAI-1, increase F-VII, increase fibrinogen, increase vWF, increase adhesion molecules), endothelial dysfunction, hyperuricemia, and increased hsC-RP and cytokines. The metabolic syndrome-X may lead to the development of T2DM and coronary heart disease (CHD); insulin resistance plays pivotal roles in the progression of such a syndrome and cardiovascular diseases. Improvement of Insulin Resistance, therefore, is most likely to reduce the high cardiovascular event rate in T2DM. It has been generally accepted that Insulin Resistance (detected by HOMA-R) and Acute Insulin Response = AIR (by HOMA-B) are both usually present in T2DM. The Thiazolidinedions (TZDs) are Insulin Sensitizers (e.g Rosiglitazone = ROS, Pioglitazone = PIO) introduced into clinical practice in 1997; clinical evidence data showed that TZDs improved both HOMA-R, and HOMA-B. PPARgamma can be activated by TZDs and it appears to be fundamental to the pathophysiology of diabetes mellitus i.e increase GLUT-4, increase glucokinase, decrease PEPCK, increase GLUT-4, and decreases production by fat cell of several mediators that may cause insulin resistance, such as TNFalpha and resistin. PPARgamma also mediates increased production of Adiponectin and the insulin signaling intermediate PI3K, and both actions lead to increase insulin sensitivity. A "dual PPARgamma-PPARalpha agonists" (e.g PIO, but ROS poorly activate PPARalpha) might lower glucose and modulate lipids. Thus, PIO, as a stronger "dual PPARgamma-PPARalpha agonists", shows an important therapeutic pathway in diabetes mellitus and cardiovascular diseases, even in metabolic syndrome. Current evidence suggests a close relationship between activation of PPARgamma and restoration of insulin sensitivity by reductions in TNFalpha and FFAs, and the enhancement of insulin stimulation of PI3-K Pathway and also increase adiponectin & decrease resistin.
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PMID:New approach in the treatment of T2DM and metabolic syndrome (focus on a novel insulin sensitizer). 1711 68

A new concept has been proposed to capture the flow of events and chain reactions associated with cardiovascular risk: the metabolic domino. The metabolic domino differs for each individual based on their genetic predisposition. Lifestyle changes are the first dominoes to fall, which lead to obesity and insulin resistance, followed by postprandial hyperglycemia, hypertension, and hyperlipidemia. Atherosclerosis then begins, and diabetes occurs once the domino for impairment of insulin secretion has toppled. Progression of the atherosclerotic process can lead to cardiovascular events such as ischemic heart diseases or cerebrovascular disorders. Preclinical and clinical data indicate that treatments which inhibit the renin angiotensin system, such as angiotensin receptor blockers, can suppress the onset of diabetes and, when administered even earlier in the metabolic domino, reduce the development of hypertension in at-risk individuals. The inhibition of inflammation with thiazolidinedione can also block the sequence of events leading to cardiovascular outcomes, as was shown with pioglitazone in the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive).
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PMID:Metabolic domino: new concept in lifestyle medicine. 1724 76

Inhibition of the renin-angiotensin system reportedly exerts potent antiatherogenic effects by reducing vascular inflammation. We tested the hypothesis that pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, further reduces vascular inflammation in patients receiving angiotensin II receptor blockers. Patients with hypertension who had developed type 2 diabetes mellitus were randomly assigned to receive either pioglitazone (15 mg/d, n = 20) or voglibose, an alpha-glucosidase inhibitor (0.6 mg/d, n=19) for 6 months, and changes in their serum concentrations of C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were monitored. Pioglitazone, but not voglibose, reduced CRP levels within 1 month (-51%+/-7%, mean+/-SEM; P<.001). C-reactive protein levels were decreased after 6 months of treatment with either pioglitazone or voglibose, with the former being more effective (-57%+/-8% vs -9%+/-18%; P<.05). The levels of ICAM-1 and VCAM-1 were significantly reduced after 1 month of pioglitazone therapy (-9%+/-3% and -8%+/-3%, respectively; both P<.05), with the beneficial effects persisting throughout the study period. In contrast, the levels of ICAM-1 and VCAM-1 were not altered during the study period in patients on voglibose. There was no correlation between the reduction of hemoglobin A1c and that of CRP, ICAM-1, or VCAM-1. These results suggest that augmentation with pioglitazone further reduces vascular inflammation in patients with hypertension and diabetes who are receiving angiotensin II receptor blockers. This may contribute to the reduction of cardiovascular events in this at-risk population.
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PMID:Pioglitazone produces rapid and persistent reduction of vascular inflammation in patients with hypertension and type 2 diabetes mellitus who are receiving angiotensin II receptor blockers. 1737 17

The recent analysis of the French MONICA registries report a reduction in the incidence of fatal MI related to improvement of care whereas the overall incidence of coronary events remain stable, suggesting the need for a better primary prevention. The extensive review of the death certificates and the analysis of the death classification from the same registries indicate an under estimation of MI-related death in the national death registry. It is also confirmed that instead of 50%, approximately 80% of coronary death are explained by the four major risk factors including smoking, hypercholesterolemia, hypertension and diabetes. The international REACH registry has enrolled more than 67 000 individuals including patients with symptomatic atherothrombotic disease and patients with multiple risk factors. The analysis of baseline characteristics and of the one year FU shows a high residual risk and a lack of efficacy of secondary prevention. The existence of a symptomatic disease and the number of symptomatic localization of atherothrombosis are critical factors to predict recurrence of major vascular events Secondary analysis of the INTERHEART study provide the essence of what should any physician know about the relationship between coronary heart disease and smoking, either active or passive. Prevention with respect to this risk factor remains very insufficient. Varenicline, a new nicotinic receptor partial agonist, should help patients involved in smoking cessation program. The established detrimental effects of perioperative smoking represent a unique opportunity to promote smoking cessation in individuals scheduled for surgery. The major cardiovascular impact of second hand smoking has been recently demonstrated by the short-term effects of banning smoking in public places on the incidence of acute coronary events. The SPARCL study has demonstrated the benefit of high dose of atorvastatine to prevent recurrent acute ischemic cerebrovascular event in patients with a prior history of stroke or TIA. In the open ASTEROID study, high doses of rosuvastatine confirm the possibility of reducing the volume of coronary atheroma analyzed by IVUS. The expected benefit of glitazones to reduce the incidence of death, MI and stroke in diabetes patients with a prior history of vascular event has been confirmed in the PROactive study. Pioglitazone provided a clear reduction of recurrent vascular events in diabetes patient with a prior MI at a cost of a significant increase of the risk of heart failure. In the DREAM study, neither ramipril nor rosiglitazone have reduced the incidence of cardiovascular events significantly. The moderate benefit of the fenofibrate to prevent cardiovascular events in the FIELD study, which was carried out in diabetics mostly in primary prevention, needs to be considered after adjustment on statin use in a higher proportion of patients of the placebo group. Postprandial hyperglycaemia, analyzed by the peak of glycaemia after a load in glucose, has been confirmed as a more powerful independent predictive factor of the risk of cardiovascular event than fasting glycaemia. The systematic screening postprandial hyperglycaemia represents an interesting strategy for primary prevention which warrants further investigation. If obesity is a risk factor whose impact on morbi-mortality is well established, a French study shows that body mass index has an unfavourable influence on the cognitive functions in middle-aged men and women.
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PMID:[The best of epidemiology and cardiovascular prevention in 2006]. 1740 66


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