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

Atrial fibrillation (AF) is the most common disorder of cardiac rhythm and is responsible for substantial morbidity and mortality in general population. A recent community-based observational study revealed that diabetes and/or hypertension were associated with the development of AF. However, there is no definite evidence to show that patients with type 1 diabetes have an increased risk for the development of AF. These findings suggest that hyperglycemia per se may not explain the positive association between diabetes and AF. Growing body of evidence supports the presence of insulin resistance as the fundamental pathophysiological disturbance responsible for the metabolic syndrome, a constellation of metabolic disorders such as hypertension, dyslipidemia, and obesity that raise the risk for diabetes mellitus and cardiovascular diseases. Further, several clinical trials have shown that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of insulin resistance. These observations suggest that insulin resistance could account for the increased risk for AF in the patients with diabetes and/or hypertension and that the interruption of the RAS may be a promising therapeutic strategy for preventing the development of AF. In the first part of this paper, we review clinical studies to support the concept that angiotensin II type 1 receptor blockers (ARBs) could prevent the development of AF in insulin resistant patients and discuss the possible underlying mechanisms. In the second part, we discuss the potential utility of telmisartan, a unique ARB with peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-modulating activity, for blocking the development of AF in patients with insulin resistance.
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PMID:Possible molecular mechanisms by which angiotensin II type 1 receptor blockers (ARBs) prevent the development of atrial fibrillation in insulin resistant patients. 1879 76

Using the cardio-ankle vascular index (CAVI) as an indicator, we assessed improvement of arterial stiffness in 95 outpatients with hypertension complicated by type 2 diabetes mellitus who were treated orally for >or= 12 months with telmisartan 40 mg/day, losartan 50 mg/day or candesartan 8 mg/day. At 1 year, in the telmisartan and losartan groups CAVI did not change whereas in the candesartan group CAVI showed a statistically significant decrease of 2.70%. Although telmisartan is believed to enhance the activity of peroxisome proliferator-activated receptor (PPAR-gamma) in vitro, it did not ameliorate arterial stiffness in our patients. Candesartan, however, improved arterial stiffness independently of blood pressure lowering and without PPAR-gamma agonist action, possibly by direct action resulting from its potent affinity and binding capacity for the angiotensin II type 1 receptor. We conclude that candesartan is a potentially useful therapy against arterial stiffness in hypertensive patients with type 2 diabetes mellitus.
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PMID:Relative effects of telmisartan, candesartan and losartan on alleviating arterial stiffness in patients with hypertension complicated by diabetes mellitus: an evaluation using the cardio-ankle vascular index (CAVI). 1883 6

Despite remarkable progress in diagnosis and understanding of risk factors, cardiovascular disease (CVD) remains still the leading cause of morbidity and mortality in the world's developed countries. The metabolic syndrome, a cluster of risk factors (visceral obesity, insulin resistance, dyslipidaemia, and hypertension), is increasingly being recognized as a new risk factor for type 2 diabetes and atherosclerotic cardiovascular disease. Nevertheless, there is wide variation in both the occurrence of disease and age of onset, even in individuals who display very similar risk profiles. There is now compelling evidence that a complex interplay between genetic determinants and environmental factors (still largely unknown) is the reason for this large inter-individual variation in disease susceptibility. The purpose of the present review is to describe the current status of our knowledge concerning the gene-environment interactions potentially implicated in the pathogenesis of metabolic syndrome, diabetes and cardiovascular disease. It focuses predominantly on studies of genes (peroxisome proliferator-activated receptor-gamma, alcohol dehydrogenase type 1C, apolipoprotein E, glutathione S-transferases T1 and M1) that are known to be modified by dietary and lifestyle habits (fat diet, intake of alcohol and smoking habit). It also describes the limited current understanding of the role of genetic variants of xenobiotic metabolizing enzymes and their interactions with environmental toxicants. Additional studies are needed in order to clarify whether inter-individual differences in detoxification of environmental toxicants may have an essential role in the development of CVD and contribute to the emerging field of "environmental cardiology". Such knowledge may be particularly relevant for improving cardiovascular risk stratification and conceiving the development of "personalized intervention program".
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PMID:Metabolic syndrome, diabetes and atherosclerosis: influence of gene-environment interaction. 1902 10

Angiotensin type 1 receptor blockers are widely used for the treatment of hypertension, and one angiotensin type 1 receptor blocker, telmisartan, specifically activates the peroxisome proliferator-activated receptor (PPAR)-gamma. We studied the impact of PPARgamma mutants on transcriptional control and interaction with cofactors to elucidate differences in the molecular mechanism between telmisartan and other PPARgamma agonists, thiazolidinediones (TZDs). We created several amino acid substitutions in the ligand binding domain of PPARgamma that, based on molecular modeling, may affect the binding of these agents. In transient expression experiments, wild-type PPARgamma-mediated transcription stimulated by telmisartan was more than one third of that stimulated by TZDs. The activation stimulated by TZDs was impaired, whereas activation stimulated by telmisartan was retained, in the H323Y, S342A, and H449A mutants. In the Y473A mutant, the TZD-induced activation was further impaired and lower than that of telmisartan-induced activation. Coexpression of coactivators enhanced the activation by both telmisartan and TZDs, but activation by telmisartan always exceeded that of TZDs in the Y473A mutant. Based on a mammalian two-hybrid assay, the interaction with corepressors was retained in Y473A. Telmisartan and TZDs, but not 9cis retinoic acid, dissociated corepressors from the wild-type PPARgamma. Telmisartan most effectively dissociated corepressors from Y473A. The interaction with coactivators was enhanced by TZD activation of wild-type PPARgamma and both telmisartan and TZD activation of Y473A. Thus, the Y473A mutant is selectively stimulated by telmisartan but not TZDs, suggesting that telmisartan and TZDs have differential effects on the transcriptional control. In conclusion, these PPARgamma mutants could be powerful tools for developing novel therapeutic agents that retain the metabolic efficacy of PPARgamma activation with fewer adverse effects, such as the increase in body weight associated with TZDs.
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PMID:A selective peroxisome proliferator-activated receptor-gamma modulator, telmisartan, binds to the receptor in a different fashion from thiazolidinediones. 1914 80

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that predominantly affects women during their reproductive years. Although SLE can affect any organ system, the kidneys are prominently involved in the form of immune complex glomerulonephritis. In addition, in women with SLE, risk for the development of cardiovascular disease is dramatically increased. Hypertension is a major risk factor for cardiovascular disease and is highly prevalent in women with SLE. Nevertheless, there has been little exploration of the pathophysiological mechanisms that promote SLE hypertension. This review discusses the role of several mechanisms, with an emphasis on the kidney, in SLE hypertension. These mechanisms include the renin-angiotensin system, endothelin, oxidative stress, sex steroids, metabolic changes, peroxisome proliferator-activated receptor-gamma, and, perhaps most importantly, chronic inflammation and cytokines. Growing evidence suggests a link between chronic inflammation and hypertension. Therefore, elucidation of mechanisms that promote SLE hypertension may be of significant value not only for patients with SLE, but also for a better understanding of the basis for essential hypertension.
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PMID:The pathophysiology of hypertension in systemic lupus erythematosus. 1915 8

Among angiotensin receptor blockers (ARBs), telmisartan is suggested to function as a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR gamma) and to improve lipid and glucose metabolism. Clinical benefits of telmisartan over other ARBs may be apparent in combination with diuretics, which have harmful influences on lipid and glucose metabolism. In the present study, 21 patients treated with mild to moderate hypertension (13 women and 8 men aged 63.1 +/- 11.6 years) underwent a 24-week treatment period with telmisartan 40 mg and HCTZ 12.5 mg once daily, or a 24-week treatment period with losartan 50 mg and HCTZ 12.5 mg once daily, without a wash-out period, in a quasi-randomized cross-over manner. Their ambulatory blood pressure and metabolic parameters were measured after the 2 treatment periods. Ambulatory systolic and diastolic blood pressures did not differ significantly between the 2 treatment periods during 24 hours, daytime, night-time, and early-morning hours (06:00-08:00). Serum uric acid was insignificantly higher in the treatment period with telmisartan/HCTZ than in the treatment period with losartan/HCTZ (P = 0.086). Although serum total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol did not differ significantly, serum triglycerides were slightly higher in the treatment period with telmisartan/HCTZ than in the treatment period with losartan/HCTZ (P = 0.060). Parameters of glucose metabolism did not differ significantly between the 2 treatment periods. In conclusion, antihypertensive efficacy was similar between the 2 regimens throughout 24 hours, despite different elimination half-lives of telmisartan and losartan. Although telmisartan is suggested to function as a partial agonist of PPARgamma, no clinical benefit was found in combination with HCTZ with respect to lipid and glucose metabolism.
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PMID:Comparison of therapies between fixed-dose telmisartan/hydrochlorothiazide and losartan/hydrochlorothiazide in patients with mild to moderate hypertension. 1924 49

Telmisartan, an angiotensin II type 1 receptor antagonist, was reported to be a partial agonist of peroxisome proliferator-activated receptor-gamma. Although peroxisome proliferator-activated receptor-gamma activators have been shown to have an anti-inflammatory effect, such as inhibition of cytokine production, it has not been determined whether telmisartan has such effects. We examined whether telmisartan inhibits expression of interleukin-6 (IL-6), a proinflammatory cytokine, in vascular smooth muscle cells. Telmisartan, but not valsartan, attenuated IL-6 mRNA expression induced by tumor necrosis factor-alpha (TNF-alpha). Telmisartan decreased TNF-alpha-induced IL-6 mRNA and protein expression in a dose-dependent manner. Because suppression of IL-6 mRNA expression was prevented by pretreatment with GW9662, a specific peroxisome proliferator-activated receptor-gamma antagonist, peroxisome proliferator-activated receptor-gamma may be involved in the process. Telmisartan suppressed IL-6 gene promoter activity induced by TNF-alpha. Deletion analysis suggested that the DNA segment between -150 bp and -27 bp of the IL-6 gene promoter that contains nuclear factor kappaB and CCAAT/enhancer-binding protein-beta sites was responsible for telmisartan suppression. Telmisartan attenuated TNF-alpha-induced nuclear factor kappaB- and CCAAT/enhancer-binding protein-beta-dependent gene transcription and DNA binding. Telmisartan also attenuated serum IL-6 level in TNF-alpha-infused mice and IL-6 production from rat aorta stimulated with TNF-alpha ex vivo. These data suggest that telmisartan may attenuate inflammatory process induced by TNF-alpha in addition to the blockade of angiotensin II type 1 receptor. Because both TNF-alpha and angiotensin II play important roles in atherogenesis through enhancement of vascular inflammation, telmisartan may be beneficial for treatment of not only hypertension but also vascular inflammatory change.
Hypertension 2009 May
PMID:Inhibition of tumor necrosis factor-alpha-induced interleukin-6 expression by telmisartan through cross-talk of peroxisome proliferator-activated receptor-gamma with nuclear factor kappaB and CCAAT/enhancer-binding protein-beta. 1928 54

Blood pressure (BP) is one of the most important and common vascular risk factors but it is often poorly controlled. Inhibition of the renin-angiotensin-aldosterone system (RAAS) provides beneficial effects in hypertensives. The association of low-dosed diuretics in combination with RAAS blocking agents allows maximum benefit from potassium depletion and control of compensatory increase in renin secretion, so increasing the efficacy and safety of RAAS blockers. Irbesartan is a potent and selective angiotensin II subtype 1 receptor antagonist indicated for use in patients with hypertension, including those with type 2 diabetes mellitus and nephropathy. Once-daily irbesartan administration provides 24h control of BP. In patients with mild-to-moderate hypertension, irbesartan was as effective as enalapril, atenolol and amlodipine, and more effective than losartan and valsartan in terms of absolute reduction in BP and response rate. Irbesartan also induced regression of left ventricular hypertrophy. Moreover, irbesartan 300 mg/day exerts a significant renoprotective effect in hypertensive type 2 diabetic patients. The relative risk of doubling of serum creatinine was significantly lower with irbesartan than amlodipine or placebo. Irbesartan was also effective in non-diabetic nephropatic patients. Moreover, irbesartan has peroxisome proliferator-activated receptor agonistic effects in in vitro studies, and it also demonstrated beneficial effects on inflammatory markers of atherosclerosis and endothelial function. The overall incidence of adverse events is similar to that of placebo. A fixed dose of hydrochlorothiazide (HCTZ) and irbesartan shows additive antihypertensive effect in a dose dependent manner up to HCTZ 25 mg and irbesartan 300 mg with high tolerability in diverse patient groups. Combination effects on end organ protection must be evaluated by broad spectrum studies. Ongoing trials about irbesartan and its combination with diuretics may provide necessary data to interpret the value of this association among others.
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PMID:Irbesartan and hydrochlorothiazide association in the treatment of hypertension. 1986 79

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. 1941 Jan 60

Telmisartan is an angiotensin-II type 1 receptor (AT1R) blocker, currently used to treat patients with hypertension. Telmisartan, in addition to its effect on AT1R, is thought to activate the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR gamma), thereby acting as a partial PPAR gamma agonist. This study was conducted to examine whether telmisartan might suppress cytokine-induced inflammatory signaling in vascular endothelial cells, thereby attenuating cellular inflammation possibly by PPAR gamma activation. Telmisartan caused a dose-dependent suppression of the tumor necrosis factor-alpha (TNFalpha)-induced activation of nuclear factor (NF)-kappaB in vascular endothelial cells in this study. The PPAR gamma antagonist, GW9662, did not influence the inhibitory effect of telmisartan on NF-kappaB activation. The thiazolidinediones neither influenced TNFalpha-induced NF-kappaB activation nor influenced the inhibitory effect of telmisartan in this process. Telmisartan dose dependently diminished the TNFalpha-induced gene expression of VCAM-1, and GW9662 did not attenuate this effect. Thus, telmisartan inhibits the cytokine-induced expression of the VCAM-1 gene by blocking NF-kappaB activation independently of PPAR gamma activation. Although the mechanism by which this occurs remains unclear, our findings suggest that telmisartan-induced anti-inflammatory effects might have favorable effects on vasculature in hypertensive patients.
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PMID:Telmisartan inhibits cytokine-induced nuclear factor-kappaB activation independently of the peroxisome proliferator-activated receptor-gamma. 1959 May 8


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