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

Obesity is commonly associated with impaired myocardial contractile function. However, a direct link between these 2 states has not yet been established. There has been an indication that leptin, the product of the human obesity gene, may play a role in obesity-related metabolic and cardiovascular dysfunctions. The purpose of this study was to determine whether leptin exerts any direct cardiac contractile action that may contribute to altered myocardial function. Ventricular myocytes were isolated from adult male Sprague-Dawley rats. Contractile responses were evaluated by use of video-based edge detection. Contractile properties analyzed in cells electrically stimulated at 0.5 Hz included peak shortening, time to 90% peak shortening, time to 90% relengthening, and fluorescence intensity change. Leptin exhibited a dose-dependent inhibition in myocyte shortening and intracellular Ca(2+) change, with maximal inhibitions of 22.4% and 26.2%, respectively. Pretreatment with the NO synthase inhibitor N:(omega)-nitro-L-arginine methyl ester (L-NAME, 100 micromol/L) blocked leptin-induced inhibition of both peak shortening and fluorescence intensity change. Leptin also stimulated NO synthase activity in a time- and concentration-dependent manner, as reflected in the dose-related increase in NO accumulation in these cells. Addition of an NO donor (S-nitroso-N-acetyl-penicillamine [SNAP]) to the medium mimicked the effects of leptin administration. In summary, this study demonstrated a direct action of leptin on cardiomyocyte contraction, possibly through an increased NO production. These data suggest that leptin may play a role in obesity-related cardiac contractile dysfunction.
Hypertension 2000 Oct
PMID:Leptin attenuates cardiac contraction in rat ventricular myocytes. Role of NO. 1104 Feb 26

Leptin, a peptide hormone produced mainly in fat cells, appears to be important for the regulation of metabolism, insulin secretion/sensitivity and body weight. Recently, elevated plasma leptin levels have been reported in patients with arterial hypertension. Because a change in circulating leptin concentrations in such patients could be caused by altered rates of production or disposal, or both, the aim of the present study was to identify regions of leptin overflow into the bloodstream and of leptin extraction. Patients with arterial hypertension (n=12) and normotensive controls (n=20) were studied during catheterization with elective blood sampling from different vascular beds (artery, and renal, hepatic, iliac and cubital veins). Plasma leptin was determined by a radioimmunoassay. Patients with hypertension had significantly elevated levels of circulating leptin (12.8 ng/l, compared with 4.1 ng/l in the controls; P<0.001), and this was also the case when adjusted for body mass index (BMI) [0.435 and 0.167 ng/l per unit BMI (kg/m(2)) respectively; P<0.001]. Circulating leptin was directly related to arterial blood pressure (r=0.38-0.62, P</=0.05-0.005) and immunoreactive insulin (r=0.51, P<0.62), but not to plasma renin activity. A significant renal extraction ratio for leptin was seen in the hypertensive patients, but this was not significantly lower than that in the controls (0.09 compared with 0. 16; P=0.1). The hypertensive patients had a significantly higher hepatic venous/arterial leptin ratio than the controls (1.02 compared with 0.93; P<0.02), and this ratio was correlated directly with the BMI (r=0.38, P=0.05) and immunoreactive insulin (r=0.43, P<0.05). In both hypertensive patients and controls there was a significant spillover of leptin into the iliac vein, but not into the cubital vein. In conclusion, the high concentration of circulating leptin in patients with arterial hypertension is probably caused by increased release of leptin from abdominal (especially mesenteric and omental) and gluteal adipose tissue stores, and renal extraction is slightly reduced. Leptin kinetics in arterial hypertension require further investigation.
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PMID:Elevated circulating leptin levels in arterial hypertension: relationship to arteriovenous overflow and extraction of leptin. 1109 96

Obesity is a major public health problem in Western countries, and >55% of adult Americans are overweight or obese. A major contributor to the epidemic of obesity is the current environment, which is characterized by increased availability of high energy foods and decreased physical activity. Several studies also demonstrated that genetic susceptibility contributes to obesity in some populations. Obesity research has focused primarily on the role of the hypothalamus in neuroendocrine regulation of food intake. However, a growing number of studies support a potential contribution of adipose tissue, via its newly discovered secretory function, to the pathogenesis of obesity and co-morbid conditions including cardiovascular disease, diabetes and hypertension. This paper will review the role of four factors secreted by adipose tissue (leptin, agouti, angiotensin II and prostaglandins) and their functions in the regulation of energy balance and whole-body homeostasis. Several other peptide and nonpeptide substances are secreted from adipose tissue; their function and regulation have been documented extensively.
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PMID:Secretory, endocrine and autocrine/paracrine function of the adipocyte. 1111 Aug 81

We determined the central interactions of neuropeptide Y and leptin on cardiovascular and sympathetic responses in conscious rabbits. Intracerebroventricular injections of neuropeptide Y (0.1 and 1 nmol/40 microL) elicited dose-related decreases in arterial pressure and renal sympathetic nerve activity without a significant change in heart rate. Peak depressor or sympathoinhibitory responses of mean arterial pressure and renal sympathetic nerve activity (-13.0+/-1.5 mm Hg and -27.6+/-4.9%) were observed at 25 and 20 minutes after intracerebroventricular injection of 1 nmol of neuropeptide Y, respectively. Pretreatment with intracerebroventricular injection of leptin (3 nmol) prevented the depressor and sympathoinhibitory responses elicited by intracerebroventricular neuropeptide Y. Intravenous injection of the same dose of neuropeptide Y (1 nmol) as that used in the intracerebroventricular experiment failed to cause any cardiovascular and renal sympathetic nerve responses. On the other hand, a subdepressor dose of intracerebroventricular infusion of neuropeptide Y (1 nmol/300 microL per hour) significantly attenuated the baroreflex sensitivities assessed by renal sympathetic nerve activity and heart rate compared with vehicle infusion (G(max); -7.4+/-0.7 versus -13.7+/-0.9%/mm Hg, P:<0.01, and -4.0+/-0.3 versus -6.7+/-0.8 bpm/mm Hg, P:<0.05, respectively). These results suggest that central neuropeptide Y participates in the regulations of the sympathetic nerve activity to kidney and the baroreceptor reflex and that the depressor response induced by intracerebroventricular neuropeptide Y is modulated, at least in part, by central leptin in conscious rabbits.
Hypertension 2000 Dec
PMID:Central cardiovascular action of neuropeptide Y in conscious rabbits. 1111 22

Recent research has emphasized the importance of the metabolic cluster, which includes glucose intolerance, dyslipidemia, and high blood pressure, as a strong predictor of the obesity-related morbidities and premature mortality. Fundamental to this association, commonly referred to as the metabolic syndrome, is the close interaction between abdominal fat patterning, total body adiposity, and insulin resistance. As the initial step in identifying major genetic loci influencing these phenotypes, we performed a genomewide scan by using a 10-centiMorgan map in 2,209 individuals distributed over 507 nuclear Caucasian families. Pedigree-based analysis using a variance components linkage model demonstrated a quantitative trait locus (QTL) on chromosome 3 (3q27) strongly linked to six traits representing these fundamental phenotypes [logarithm of odds (lod) scores ranged from 2.4 to 3.5]. This QTL exhibited possible epistatic interaction with a second QTL on chromosome 17 (17p12) strongly linked to plasma leptin levels (lod = 5.0). Situated at these epistatic QTLs are candidate genes likely to influence two biologic precursor pathways of the metabolic syndrome.
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PMID:Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. 1112 Oct 50

The common syndrome of insulin resistance is frequently seen in obese individuals, and is characterized by glucose intolerance, dyslipidemia, high blood pressure, and an increased risk of coronary heart disease. A rare genetic form of insulin resistance is Dunnigan-type familial partial lipodystrophy (FPLD; OMIM #151660), which is characterized by loss of subcutaneous fat from extremities, trunk, and gluteal region, and always by insulin resistance and hyperinsulinemia, often with hypertension, dyslipidemia, type-2 diabetes and early endpoints of atherosclerosis. FPLD was recently discovered to result from mutated LMNA (R482Q; OMIM #150330.0010), which is the gene encoding nuclear lamins A and C. Results from extended pedigrees indicate that dyslipidemia precedes the plasma glucose abnormalities in FPLD subjects with mutant LMNA, and that the hyperinsulinemia is present early in the course of the disease. Plasma leptin is also markedly reduced in subjects with FPLD due to mutant LMNA. Thus, rare mutations in a nuclear structural protein can be associated with markedly abnormal qualitative and quantitative phenotypes, indicating that a defect in the structure and function of the nuclear envelope can result in a phenotype that shares many aspects with the common syndrome of insulin resistance.
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PMID:Insulin resistance in human partial lipodystrophy. 1112 71

Longitudinal and cross-sectional studies suggest that a large number of obese patients have a high prevalence of hypertension. This association causes the following changes: insulin and leptin resistance with a suppressed biologic activity of natriuretic peptide, which contributes to sodium retention with concomitant expanded cardiopulmonary volume and increased cardiac output. The cellular metabolism of cations may be altered in obesity and may lead to changes in vascular responsiveness and increased vascular resistance. These changes lead to structural adaptations in the heart characterized by concentric-eccentric left ventricular hypertrophy. The hypertrophic condition provides the basis for the development of congestive heart failure and cardiac arrhythmias that may explain the higher rates of cardiac sudden death in those patients. In the kidneys, obesity hypertension may initiate a derangement of renal function. The increased deposit of interstitial cells and of extracellular matrix between the tubules induces higher interstitial hydrostatic pressure and tubular sodium reabsorption. The consequent increase in renal flow and glomerular filtration enhances albuminuria excretion and the susceptibility to the development of renal damage. In summary, the hemodynamic and structural adaptations related to obesity hypertension is the cause of greater risk for adverse cardiovascular and renal events.
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PMID:Obesity-hypertension: the effects on cardiovascular and renal systems. 1113 Jul 76

Dunnigan-type familial partial lipodystrophy (FPLD; OMIM 151660) is a rare monogenic form of insulin resistance characterized by loss of subcutaneous fat from the extremities, trunk, and gluteal region. FPLD recapitulates the main metabolic attributes of the insulin resistance syndrome, including central obesity, hyperinsulinemia, glucose intolerance and diabetes, dyslipidemia, and hypertension. Through the use of focused DNA sequencing of positional candidate genes on chromosome 1q21, we discovered that FPLD results from mutations in LMNA (R482Q; OMIM 150330.0010), which is the gene that encodes nuclear lamins A and C. By stratifying members of extended FPLD pedigrees according to LMNA genotype, we found that hyperinsulinemia is present early in the course of the disease and that dyslipidemia (characterized by high triglycerides and depressed HDL cholesterol) precedes the development of glucose abnormalities. Plasma leptin is also markedly reduced in subjects with FPLD due to mutant LMNA. The findings in FPLD indicate that defective structure of the nuclear envelope produces a phenotype of insulin resistance. The findings may have relevance for common insulin resistance and for drug-associated lipodystrophies, whose molecular basis is unknown at present.
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PMID:Familial partial lipodystrophy: a monogenic form of the insulin resistance syndrome. 1113 44

The incidence of obesity (especially childhood obesity) and its associated health-related problems have reached epidemic proportions in the United States. Recent investigations suggest that the causes of obesity involve a complex interplay of genetic, environmental, psychobehavioral, endocrine, metabolic, cultural, and socioeconomic factors. Several genes and their protein products, such as leptin, may be particularly important in appetite and metabolic control, although the genetics of human obesity appear to involve multiple genes and metabolic pathways that require further elucidation. Severe obesity is frequently associated with significant comorbid medical conditions, including coronary artery disease, hypertension, type II diabetes mellitus, gallstones, nonalcoholic steatohepatitis, pulmonary hypertension, and sleep apnea. Long-term reduction of significant excess weight in these patients may improve or resolve many of these obesity-related health problems, although convincing evidence of long-term benefit is lacking. Available treatments of obesity range from diet, exercise, behavioral modification, and pharmacotherapy to surgery, with varying risks and efficacy. Nonsurgical modalities, although less invasive, achieve only relatively short-term and limited weight loss in most patients. Currently, surgical therapy is the most effective modality in terms of extent and duration of weight reduction in selected patients with acceptable operative risks. The most widely performed surgical procedure, Roux-en-Y gastric bypass, achieves permanent (followed up for more than 14 years) and significant weight loss (more than 50% of excess body weight) in more than 90% of patients.
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PMID:Current status of medical and surgical therapy for obesity. 1117 43

Pregnancy-induced hypertension (PIH), which includes both gestational hypertension and preeclampsia, is a common and morbid pregnancy complication for which the pathogenesis remains unclear. Emerging evidence suggests that insulin resistance, which has been linked to essential hypertension, may play a role in PIH. Conditions associated with increased insulin resistance, including gestational diabetes, polycystic ovary syndrome, and obesity, may predispose to hypertensive pregnancy. Furthermore, metabolic abnormalities linked to the insulin resistance syndrome are also observed in women with PIH to a greater degree than in normotensive pregnant women: These include glucose intolerance, hyperinsulinemia, hyperlipidemia, and high levels of plasminogen activator inhibitor-1, leptin, and tumor necrosis factor-alpha. These observations suggest the possibility that insulin resistance may be involved in the pathogenesis of PIH and that approaches that improve insulin sensitivity might have benefit in the prevention or treatment of this syndrome, although this requires further study.
Hypertension 2001 Feb
PMID:Brief review: hypertension in pregnancy : a manifestation of the insulin resistance syndrome? 1123 Feb 77


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