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

Studies reveals that plasma leptin levels (LEP) in females are higher than those in males, and that LEP in hypertensive subjects are higher than those in BMI-matched normotensive subjects. To investigate the relationships among LEP, blood pressure (BP) and insulin sensitivity, we studied these relationships in 133 Japanese males and 263 females. LEP were positively correlated with BP, body mass index, body fat mass (FM) and homeostasis model assessment (HOMA). Regression analysis in which age and FM were adjusted showed LEP were associated with BP and HOMA. Even with adjustment by age, FM and HOMA, LEP were still positively correlated BP in males. LEP in insulin-resistant hypertensives was significantly higher than those in insulin-sensitive hypertensives, in insulin-sensitive normotensives and in insulin-resistant normotensives in males. However, in females, a significantly higher LEP was observed in insulin-resistant subjects than in insulin-sensitive subjects regardless of hypertension. These data suggest that it would be sexual difference in the relationships among hyperleptinemia, hyperinsulinemia and hypertension.
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PMID:Gender difference in the relationships among hyperleptinemia, hyperinsulinemia, and hypertension. 1134 26

Hormonal control of the Na+,K+-pump modulates membrane potential in mammalian cells, which in turn drives ion coupled transport processes and maintains cell volume and osmotic balance. Na+,K+-pump regulation is particularly important in the musculoskeletal, cardiovascular and renal systems. Decreased Na+,K+-pump activity can result in a rise in intracellular Na+ concentrations which in turn increase Na+/Ca2+ exchange, thereby raising intracellular Ca2+ levels. In cardiac and skeletal muscle, this could interfere with normal contractile activity. Similarly, in vascular smooth muscle the result would be resistance to vasodilation. Inhibition of the Na+,K+-pump can also reduce the driving force for renal tubular Na+ reabsorption, elevating Na+ excretion. By virtue of decreasing the membrane potential, thus allowing more efficient depolarization of nerve endings and by increasing intracellular Ca2+, inhibition of the Na+,K+-pump can increase nervous tone. The ability of insulin to stimulate the Na+,K+-pump in various cells and tissues, and the physiological significance thereof, have been well documented. Much less is known about the effect of leptin on the Na+,K+-pump. We have shown that leptin inhibits Na+,K+-pump function in 3T3-L1 fibroblasts. Defects in insulin and leptin action are associated with diabetes and obesity, respectively, both of which are commonly associated with cardiovascular complications. In this review we discuss the mechanisms of Na+,K+-pump regulation by insulin and leptin and highlight how, when they fail, they may contribute to the pathophysiology of hypertension associated with diabetes and obesity.
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PMID:Mechanisms and consequences of Na+,K+-pump regulation by insulin and leptin. 1135 12

The cytokine receptors for growth hormone (GH), prolactin and leptin have a critical role in regulating embryo, placental and/or fetal development, which is dependent on stage of gestation and species. GH and prolactin receptors are detectable from conception, and alterations in the maternal hormonal environment may impact on placental growth from this early stage of gestation. Leptin is critical for conception, but its role in fetal growth remains elusive. During late gestation, when fetal growth accelerates and organ maturation occurs, prolactin and insulin-like growth factor-I may have interactive roles in regulating the growth of specific tissues, including adipose tissue. Prolactin, leptin and GH all have specific effects on fetal and neonatal energy balance, which are mediated in part through promoting lipolysis and/or enhancing the expression of uncoupling proteins. An increased understanding of these interactions is likely to have important implications for a number of potentially pathological conditions, including infection, obesity and hypertension.
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PMID:Cytokines and cytokine receptors in fetal growth and development. 1135 22

Insulin resistance and hyperinsulinemia have been observed in essential hypertension. The selective impairment of glucose metabolism in skeletal muscle may accompanied hyperinsulinemia and raise blood pressure through sympathetic nervous system and/or renin-angiotensin system activation, renal sodium retention, proliferation of vascular smooth muscle and leptin. Recently, molecular techniques have applied for investigating the mechanisms of insulin resistance. The mutation of insulin receptor gene, changes of muscle fiber composition and muscle blood flow, abnormalities of insulin signal transduction, and TNF-alpha are considered as involvement of insulin resistance in the skeletal muscle. While further study will be necessary to clarify the mechanisms of insulin resistance and hypertension.
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PMID:[Insulin resistance syndrome]. 1139 82

Obesity is often accompanied with hypertension and increases cardiovascular events. Japanese new guideline on identification of obesity includes a modified BMI categories and a method of detection of visceral fat obesity in Japanese. Hyper-insulinemia and leptin released from adipose tissue play an important role in the development of hypertension in obese patients. Insulin and leptin increase sympathetic tone which results in sodium retention and hyper-responsiveness of blood vessels. As leptin has also a direct vasodilative and diuretic action, its effect on blood pressure is bidirectional. Life style modification, especially diet and physical exercise are important to obtain the body weight loss and the improvement of insulin resistance. Dynamic exercise at the level of fifty percent of max VO2 for 30 to 60 minutes over three times a week should be recommended for hypertensive patients with obesity. ACE inhibitors improve the hypersympathetic tone and impaired insulin sensitivity in obese patients. Calcium antagonist is also useful for these patients.
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PMID:[Treatment of hypertension in the patients with obesity]. 1139 1

In males, aging, health and disease are processes that occur over physiologic time and involve a cascade of hormonal, biochemical and physiological changes that accompany the down-regulation of the hypothalamic-anterior pituitary-testicular axis. As aging progresses there are relative increases of body fat and decreases in muscle mass. The increased adipose tissue mass is associated with the production of a number of newly generated factors. These include aromatase, leptin, PAI-1, insulin resistance, and the dyslipidemias, all of which can lead to tissue damage. Fatty tissue becomes the focal point for study as it represents the intersection between energy storage and mobilization. The increase in adipose tissue is associated with an increase in the enzyme aromatase that converts testosterone to estradiol and leads to diminished testosterone levels that favor the preferential deposition of visceral fat. As the total body fat mass increases, hormone resistance develops for leptin and insulin. Increasing leptin fails to prevent weight gain and the hypogonadal-obesity cycle ensues causing further visceral obesity and insulin resistance. The progressive insulin resistance leads to a high triglyceride-low HDL pattern of dyslipidemia and increased cardiovascular risk. All of these factors eventually contribute to the CHAOS Complex: coronary disease, hypertension, adult-onset diabetes mellitus, obesity and/or stroke as permanent changes unfold. Other consequences of the chronic hypogonadal state include osteopenia, extreme fatigue, depression, insomnia, loss of aggressiveness and erectile dysfunction all of which develop over variable periods of time.
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PMID:Aromatase, adiposity, aging and disease. The hypogonadal-metabolic-atherogenic-disease and aging connection. 1139 22

This study was conducted to evaluate the mechanisms of weight loss-induced blood pressure (BP) reduction focusing, in particular, on the contributions of sympathetic nervous system activity, fasting plasma insulin, and leptin to BP levels, and to delineate the additional influence of antihypertensive drug therapy. Each of five groups of obese hypertensives were treated with the long-acting calcium channel blocker (CCB) amlodipine, the angiotensin converting enzyme (ACE) inhibitor enalapril with or without a weight reduction program, or a weight reduction program alone. The goal BP was less than 140/90 mm Hg for the pharmacologic treatment groups. The weight reduction program groups with or without pharmacologic treatment were divided into two groups; weight loss groups who succeeded in weight reduction (> or = 10%) and nonweight loss groups who failed in weight reduction (<10%) in the first 6 months. The final dose of CCB and ACE inhibitor were less in the combined pharmacologic and weight loss groups than in the pharmacologic treatment alone groups or in the pharmacologic and nonweight loss groups. In the weight reduction groups regardless of pharmacologic treatment, the percent reductions from baseline in plasma insulin, leptin, and norepinephrine (NE) were greater in the weight loss groups (> or = 10%) than in the nonweight loss groups (<10%). The reductions in plasma NE, insulin, and leptin were significantly greater and earlier in combined pharmacologic and weight loss groups than in the pharmacologic treatment alone groups. In ACE inhibitor groups, the reductions in plasma NE, in insulin, and especially in leptin were greater than the other groups. In the CCB alone group, reductions in insulin and leptin occurred, but there was no change in plasma NE. Reductions in insulin and leptin in CCB groups were less and occurred later than in the ACE inhibitor groups or the weight reduction alone group. These results show that weight loss associated with favorable metabolic improvements and these improvements are amplified when combined with pharmacologic treatment. Therefore, weight loss should be regarded as an essential component of any treatment program for obesity-related hypertension. A novel finding from this study is that ACE inhibition had a striking effect to lower plasma leptin. Suppression of sympathetic activity, insulinemia, and leptinemia appeared to play a role in the BP reduction accompanying weight loss.
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PMID:Weight reduction and pharmacologic treatment in obese hypertensives. 1141 32

Obesity may account for as much as 65% to 75% of human essential hypertension in most industrialized countries. Excess renal sodium reabsorption and a hypertensive shift of renal-pressure natriuresis play a key role in mediating obesity hypertension. Sympathetic activation contributes to obesity-induced sodium retention and hypertension because adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with other neurochemical pathways in the hypothalamus may be a partial link between excess weight gain and increased sympathetic activity. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term intravenous leptin infusions in nonobese rodents at rates that raise plasma concentrations to the levels found in severe obesity increase arterial pressure and heart rate through adrenergic activation. Also, transgenic mice that overexpress leptin develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including melanocortin-4 receptors. However, it is unclear whether this pathway or others, such as neuropeptide Y, mediate the long-term effects of leptin on blood pressure. In addition, leptin has other actions, such as stimulation of nitric oxide formation and enhancement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the precise role of these complex interactions in human obesity has not been elucidated, this is an important area for further investigation, especially considering the current epidemic of obesity in most industrialized countries.
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PMID:Obesity hypertension: role of leptin and sympathetic nervous system. 1141 45

Cardiovascular risk factors cluster in obese individuals. Insulin resistance emerges as a common pathogenetic denominator underlying the risk factor cluster. Defects in nonesterified fatty acids metabolism have been implicated in the abnormal lipid and glucose metabolism which characterize the cluster. Other evidence also leads to the adipocyte as an important contributor to the risk factor cluster and cardiovascular complications through effects not only on fatty acids but also on leptin, plasminogen activator inhibitor-1, and angiotensinogen, to name a few. Fatty acids are elevated among abdominally obese individuals, are more resistant to suppression by insulin, and may contribute to hypertension. Fatty acids may affect blood pressure by inhibiting endothelial nitric oxide synthase activity and impairing endothelium-dependent vasodilation. Fatty acids increase alpha1-adrenoceptor-mediated vascular reactivity and enhance the proliferation and migration of cultured vascular smooth-muscle cells. Several effects of fatty acids are mediated through oxidative stress. Fatty acids can also interact with other facets of cluster, including increased angiotensin II, to accentuate oxidative stress. Oxidative stress, in turn, is implicated in the pathogenesis of insulin resistance, hypertension, vascular remodeling, and vascular complications. A clearer delineation of the key reactive oxygen signaling pathways and the impact of various interventions on these pathways could facilitate a rationale approach to antioxidant therapy and improved outcomes among the rapidly growing number of high-risk, insulin-resistant, obese individuals.
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PMID:Insulin resistance and cardiovascular disease. 1141 46

Patients with insulin resistance and/or type 2 diabetes have a 5-fold increase in cardiovascular mortality rate. Therefore, it is a current issue of discussion that arterial hypertension, lipid disorders as well as visceral obesity are coronary risk factors, which might belong to a syndrome that is caused by decreased insulin sensitivity. Concerning a possible molecular link between insulin resistance, atherosclerosis and obesity, we focus in our research on questions looking for a molecular link between lipid metabolism, insulin action, and obesity at a gene regulatory level. Alterations in the structure, function and regulation of transcription factors appear to be such signalling steps which might play an essential role in the pathogenesis and therapy of cardiovascular risk factors associated with insulin resistance, eg the so called metabolic syndrome. Recent examples are members of the nuclear hormone receptor superfamily, eg peroxisome proliferator-activated receptor (PPAR) isoforms and sterol regulatory element-binding proteins (SREBPs). Beside their regulation by different metabolites, these transcription factors are also targets of hormones, like insulin and leptin, growth factors, and inflammatory signals. Therefore, they appear to be a point of signalling convergence at a gene regulatory level. Major signalling pathways coupling receptors at the cell surface for hormones, growth factors as well as cytokines to gene regulatory events in the nucleus are the MAP-kinase cascades. We have recently defined different postreceptor defects in these pathways in patients with clinical phenotypes corresponding to congenital lipoatrophy. Therefore, these studies may identify novel pathways which play a role in the control of body weight, insulin sensitivity and cardiovascular risk.
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PMID:Insulin-regulated transcription factors: molecular link between insulin resistance and cardiovascular risk factors. 1146 84


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