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

Pioglitazone, a member of the PPAR-gamma agonist drug family, has been demonstrated to improve both metabolic and vascular insulin resistance when applied to patients with Type 2 diabetes mellitus. The drug is well tolerated with fluid retention and weight gain being the most frequently described side effects. The observed effects (e.g., improvements in glucose and lipid metabolism, improvements of endothelial function and microcirculation, reduction of surrogate markers of atherosclerosis and inflammation and an improvement in hypertension) have made pioglitazone one of the frequently prescribed antidiabetic drugs in the US and Europe. Several trials have shown its potency to reduce carotid intima-media thickness, and outcome studies with pioglitazone have shown its potential to delay the progression of Type 2 diabetes and atherosclerosis and even reduce cardiovascular mortality. The purpose of this review is to provide an overview about recently published clinical results with pioglitazone. They underline the value of this drug when used alone or in combination with other antidiabetic drugs for a successful management of Type 2 diabetes mellitus.
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PMID:Pioglitazone: update on an oral antidiabetic drug with antiatherosclerotic effects. 1769 99

We assessed the effect of the addition of pioglitazone on metabolic control and heart function of patients with type 2 diabetes already receiving sulfonylurea plus metformin. Forty-four patients were given 30 mg of pioglitazone for 3 months. Physical examination, laboratory tests including N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiography, were performed at baseline and at study completion. Target HbA(1c) levels were achieved by 44.2% of the patients. Pioglitazone ameliorated lipid profile and lowered liver enzymes and C-reactive protein. Significant increases in NT-proBNP by 39% (P < 0.005) were noticed, but echocardiographic parameters were not altered, even in high-risk subgroups (patients older than 60 years, with diabetes for more than 10 years, with hypertension, with elevated baseline NT-proBNP levels, with left ventricular hypertrophy). In patients with a greater than 60% increase in NT-proBNP levels, a significant increase in left ventricular ejection fraction (P < 0.05) and in fractional shortening (P < 0.05) was found. None of the patients developed edema or signs or symptoms of heart failure. Triple oral combination antidiabetic treatment is an effective therapeutic strategy and weight gain does not abrogate its beneficial actions. Pioglitazone does not affect heart function and even though it increases NT-proBNP, this appears to represent a reaction to volume overload.
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PMID:Effect of pioglitazone on heart function and N-terminal pro-brain natriuretic peptide levels of patients with type 2 diabetes. 1776 92

Beneficial effects of thiazolidinediones, peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, on cardiovascular injuries have been reported. However, the effects of these agonists on left ventricular (LV) hypertrophy have not been clarified. To investigate whether pioglitazone improves LV hypertrophy, we used 32-week-old stroke-prone spontaneously hypertensive rats (SHR-SP) that had been treated or not treated with pioglitazone (10 mg/kg/day) for 8 weeks, and Wistar Kyoto rats (WKY). We evaluated LV geometry by echocardiography; myocyte hypertrophy, tissue fibrosis, and appearance of myofibroblasts by histological examination; mRNA expression by real-time polymerase chain reaction (PCR); protein expression by Western blot; activities of matrix metalloproteinase (MMP) by zymography; and production of reactive oxygen species (ROS) by electron spin resonance spectroscopy or thiobarbituric acid reactive substances (TBARS). SHR-SP showed concentric hypertrophy of the LV, but WKY did not. The myocyte diameter, fraction of tissue fibrosis, and number of myofibroblasts were greater in SHR-SP. mRNA expressions of collagen type I and type III, tissue growth factor (TGF)-beta1, and brain natriuretic peptide (BNP); protein expression of connective tissue growth factor (CTGF); activities of MMP2 and MMP9; and ROS were increased in SHR-SP. Pioglitazone did not decrease blood pressure, but partially normalized LV geometry in addition to decreasing myocyte diameter, interstitial fibrosis and number of myofibroblasts; mRNA levels of collagen type I and BNP; MMP2 activity; and protein level of CTGF. However, the mRNA level of collagen type III and TGF-beta1, MMP9 activity, and ROS production were not improved. In conclusion, pioglitazone reversed the concentric LV remodeling independently from blood pressure or oxidative stress in chronic hypertension.
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PMID:Beneficial effects of pioglitazone on left ventricular hypertrophy in genetically hypertensive rats. 1803 80

The effect of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, on hypertensive cardiovascular injury is unknown. We examined the effect of pioglitazone on hypertensive cardiovascular injury and the significance of combination of pioglitazone with angiotensin type 1 receptor blocker. Stroke-prone spontaneously hypertensive rats (SHRSP) were orally given pioglitazone, candesartan, or combined pioglitazone and candesartan for 4 weeks to compare their effects on cardiovascular injury. Pioglitazone, without lowering blood pressure, significantly suppressed cardiac inflammation and fibrosis and reduced vascular endothelial dysfunction, and these beneficial effects were associated with the reduction of superoxide by inhibition of cardiovascular NADPH oxidase. Thus, pioglitazone protects against hypertensive cardiovascular injury, by inhibiting reactive oxygen species (ROS). Combination of pioglitazone and candesartan suppressed cardiac hypertrophy, inflammation, and interstitial fibrosis of SHRSP to a greater extent than either monotherapy, and reduced vascular endothelial dysfunction of SHRSP more than either monotherapy. Furthermore, more beneficial effects of their combination on cardiovascular injury were associated with more reduction of NADPH oxidase-mediated cardiovascular ROS. To elucidate the underlying molecular mechanism, we examined cardiovascular NADPH oxidase subunits. Pioglitazone monotherapy significantly attenuated cardiovascular p22(phox) and Rac1 in SHRSP, whereas pioglitazone combined with candesartan more attenuated p22(phox) and significantly reduced Nox1. Thus, additive suppression of cardiovascular NADPH oxidase by the combination was attributed to its additive attenuation of p22(phox) and Nox1 protein levels. In conclusion, we showed that pioglitazone protected against hypertensive cardiovascular damage, and the combination of pioglitazone and candesartan exerted more beneficial effects on hypertensive cardiovascular injury by more suppressing ROS.
Hypertension 2008 Feb
PMID:Beneficial effects of pioglitazone on hypertensive cardiovascular injury are enhanced by combination with candesartan. 1857 65

Insulin resistance, which precedes type 2 diabetes mellitus (T2DM), is a widespread pathology associated with the metabolic syndrome, myocardial ischemia, and hypertension. Finding an adequate treatment for this pathology is an important goal in medicine. The purpose of the present research was to investigate the effect of an extract from Aloe vera gel containing a high concentration of polyphenols on experimentally induced insulin resistance in mice. A polyphenol-rich Aloe vera extract (350 mg/kg) with known concentrations of aloin (181.7 mg/g) and aloe-emodin (3.6 mg/g) was administered orally for a period of 4 weeks to insulin resistant ICR mice. Pioglitazone (50 mg/kg) and bi-distilled water were used as positive and negative controls respectively. Body weight, food intake, and plasma concentrations of insulin and glucose were measured and insulin tolerance tests were performed. The insulin resistance value was calculated using the homeostasis model assessment for insulin resistance (HOMA-IR) formula. Results showed that the polyphenol-rich extract from Aloe vera was able to decrease significantly both body weight (p < 0.008) and blood glucose levels (p < 0.005) and to protect animals against unfavorable results on HOMA-IR, which was observed in the negative control group. The highest glucose levels during the insulin tolerance curve test were in the negative control group when compared to the Aloe vera extract and pioglitazone treated mice (p < 0.05). In conclusion, Aloe vera gel could be effective for the control of insulin resistance.
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PMID:Effect of a polyphenol-rich extract from Aloe vera gel on experimentally induced insulin resistance in mice. 1818 89

The metabolic syndrome is a risk factor for the development of chronic kidney disease. Angiotensin II type 1 receptor blockers (ARBs) and thiazolidinediones (TZDs) provide renovascular protection, probably in the metabolic syndrome. However, the effect of both agents administered together in patients with metabolic syndrome remains to be determined. The aim of this study was to assess the effects of ARB plus TZD combination therapy in Zucker obese rats fed a high-protein diet, an animal model of metabolic syndrome and renal injury. Zucker obese rats were fed a high-protein diet (OHP; n=6), a high-protein diet containing candesartan, an ARB (OHP+C; n=6), or a high-protein diet containing both candesartan and pioglitazone (OHP+CP; n=6) for 12 weeks. Systolic blood pressure and urinary protein excretion were measured throughout the study, and renal histology and immunohistochemistry were assessed at 12 weeks. OHP rats developed hypertension (157+/-4 mmHg) and proteinuria (178+/-44 mg/d), and these conditions were significantly ameliorated by candesartan (to 143+/-3 mmHg and 84+/-25 mg/d, respectively). Pioglitazone enhanced the antihypertensive and anti-proteinuric effects of candesartan (121+/-3 mmHg, 16+/-8 mg/d, respectively). Histologically, candesartan ameliorated glomerulosclerosis, podocyte injury, interstitial fibrosis and monocyte/macrophage infiltration into the tubulointerstitium in the kidneys of OHP rats. Pioglitazone abrogated residual interstitial fibrosis in the kidneys of OHP+C rats. Our results suggested that pioglitazone augmented the antihypertensive, anti-proteinuric and possibly renal anti-fibrotic actions of candesartan in Zucker obese rats fed a high-protein diet. The combination therapy of ARB and TZD may protect against renal injury in patients with metabolic syndrome.
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PMID:Pioglitazone enhances the antihypertensive and renoprotective effects of candesartan in Zucker obese rats fed a high-protein diet. 1863 87

Metabolic syndrome is considered as clustering of cardiovascular risk factors related to insulin resistance. Pioglitazone is one of thiazolidinediones that acts as insulin sensitizer. Since insulin resistance plays a role in pathogenesis of hypertension, pioglitazone may subserve antihypertensive effect in subjects with metabolic syndrome. We reviewed literatures about the effects of pioglitazone on blood pressure. Although blood pressure lowering effect of pioglitazone is small, several clinical trials and a meta-analysis indicated that it decreases both systolic and diastolic blood pressure. Pioglitazone has favorable effects on important components of metabolic syndrome including blood pressure.
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PMID:[Pioglitazone effects on blood pressure in patients with metabolic syndrome]. 1870 May 62

We investigated the ability of angiotensin II type 1 (AT1) receptor blockers with peroxisome proliferator-activated receptor (PPAR)-gamma agonist activity (telmisartan and irbesartan) and AT1 receptor blockers devoid of PPARgamma agonist activity (eprosartan and valsartan) to inhibit vascular cell proliferation studied in the absence of angiotensin II stimulation. Telmisartan and, to a lesser extent, irbesartan inhibited proliferation of human aortic vascular smooth muscle cells in a dose-dependent fashion, whereas eprosartan and valsartan did not. To investigate the role of PPARgamma in the antiproliferative effects of telmisartan, we studied genetically engineered NIH3T3 cells that express PPARgamma. Pioglitazone inhibited proliferation of NIH3T3 cells expressing PPARgamma but had little effect on control NIH3T3 cells that lack PPARgamma. In contrast, telmisartan inhibited proliferation equally in NIH3T3 with and without PPARgamma. Valsartan failed to inhibit proliferation of either cell line. In addition, telmisartan inhibited proliferation equally in aortic smooth muscle cells derived from mice with targeted knockout of PPARgamma in the smooth muscle and from control mice, whereas valsartan had no effect on cell proliferation. Telmisartan, but not valsartan, reduced phosphorylation of AKT but not extracellular signal-regulated kinase otherwise induced by exposure to serum of quiescent human smooth muscle cells, quiescent mice smooth muscle cells lacking PPARgamma, or quiescent Chinese hamster ovary-K1 cells lacking the AT1 receptor. In summary, the antiproliferative effects of telmisartan in the absence of exogenously supplemented angiotensin II involve more than just AT1 receptor blockade and do not require activation of PPARgamma. It might be postulated that inhibition of AKT activation is a mechanism mediating the antiproliferative effects of telmisartan, including in cells lacking AT1 receptors or PPARgamma.
Hypertension 2009 Dec
PMID:Telmisartan-induced inhibition of vascular cell proliferation beyond angiotensin receptor blockade and peroxisome proliferator-activated receptor-gamma activation. 1982 96

The favorable effects of the peroxisome proliferator-activated receptor-gamma ligand pioglitazone on glucose metabolism are associated with an increase in the fat-derived hormone adiponectin in the bloodstream. A recent clinical trial, Prospective Pioglitazone Clinical Trial in Macrovascular Events, demonstrated that pioglitazone improved cardiovascular outcomes in patients with type 2 diabetes mellitus. However, the functional role of adiponectin in cardioprotection by pioglitazone has not been examined experimentally. Here we investigated the effect of pioglitazone on angiotensin II (Ang II)-induced cardiac hypertrophy and assessed the potential contribution of adiponectin to the action of pioglitazone on the heart. Wild-type or adiponectin-deficient mice were treated with pioglitazone as food admixture at a concentration of 0.01% for 1 week followed by 2 weeks of infusion with Ang II at 3.2 mg/kg per day. Ang II infusion in wild-type mice resulted in exacerbated myocyte hypertrophy and increased interstitial fibrosis, which were accompanied by elevated phosphorylation of extracellular signal-regulated kinase and expression of transforming growth factor-beta1 in the heart. Treatment of wild-type mice with pioglitazone attenuated cardiac hypertrophy and fibrosis, extracellular signal-regulated kinase phosphorylation, and transforming growth factor-beta1 expression in response to Ang II. Pioglitazone also increased the plasma adiponectin level and phosphorylation of cardiac AMP-activated protein kinase in wild-type mice in the presence of Ang II. The suppressive effects of pioglitazone on Ang II-induced cardiac hypertrophy and fibrosis were diminished in adiponectin-deficient mice. Furthermore, pioglitazone had no effects on the phosphorylation of extracellular signal-regulated kinase and AMP-activated protein kinase in the Ang II-infused heart of adiponectin-deficient mice. These data provide direct evidence that pioglitazone protects against Ang II-induced pathological cardiac remodeling via an adiponectin-dependent mechanism.
Hypertension 2010 Jan
PMID:Evidence for the importance of adiponectin in the cardioprotective effects of pioglitazone. 1993 24

To treat metabolic syndrome, fat tissue dysfunction should be corrected rather than controlling conventional risk factors such as hypertension, dyslipidemia, and diabetes mellitus. For this purpose, accumulating evidence suggests increasing plasma adiponectin levels can be a key treatment strategy, especially in setting of food or drug selection. Here we report that adipocyte precursors obtained from several sites of fat tissue, which we call Metabolic Stem Cells (MSC), could be used as a novel screening system to identify adiponectin enhancing drugs or food for individual patients. MSC were prepared from fat tissues collected from 29 patients. They were differentiated in cultures into mature adipocytes. The time course of adiponectin production was independent of the number of mature adipocytes and gradually decreased at 48 h after differentiation. Pioglitazone, a full PPARgamma agonist, stabilized adiponectin production at days 8-16 after differentiation, whereas telmisartan, a partial PPARgamma agonist, showed variable response. Dividing the adiponectin secretion of day 12 by that of day 10 provided an estimate of adiponectin-producing activity irrespective of the number of MSC-derived adipocytes in culture. Using this score of adiponectin-production activity, we successfully assessed 16 agents in a 96-well plate. The effect of each agent on adiponectin production showed a similar pattern, independent of the site of isolated adipose tissue. Our results show that MSC can be used as a tool for selecting drugs that enhance adiponectin-production activity.
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PMID:Measurement of adiponectin production from differentiated metabolic stem cells. 2022 81


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