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

Leptin plays an important role in regulation of body weight through regulation of food intake and sympathetically mediated thermogenesis. The hypothalamic melanocortin system, via activation of the melanocortin-4 receptor (MC4-R), decreases appetite and weight, but its effects on sympathetic nerve activity (SNA) are unknown. In addition, it is not known whether sympathoactivation to leptin is mediated by the melanocortin system. We tested the interactions between these systems in regulation of brown adipose tissue (BAT) and renal and lumbar SNA in anesthetized Sprague-Dawley rats. Intracerebroventricular administration of the MC4-R agonist MT-II (200 to 600 pmol) produced a dose-dependent sympathoexcitation affecting BAT and renal and lumbar beds. This response was completely blocked by the MC4-R antagonist SHU9119 (30 pmol ICV). Administration of leptin (1000 microg/kg IV) slowly increased BAT SNA (baseline, 41+/-6 spikes/s; 6 hours, 196+/-28 spikes/s; P=0.001) and renal SNA (baseline, 116+/-16 spikes/s; 6 hours, 169+/-26 spikes/s; P=0.014). Intracerebroventricular administration of SHU9119 did not inhibit leptin-induced BAT sympathoexcitation (baseline, 35+/-7 spikes/s; 6 hours, 158+/-34 spikes/s; P=0.71 versus leptin alone). However, renal sympathoexcitation to leptin was completely blocked by SHU9119 (baseline, 142+/-17 spikes/s; 6 hours, 146+/-25 spikes/s; P=0.007 versus leptin alone). This study demonstrates that the hypothalamic melanocortin system can act to increase sympathetic nerve traffic to thermogenic BAT and other tissues. Our data also suggest that leptin increases renal SNA through activation of hypothalamic melanocortin receptors. In contrast, sympathoactivation to thermogenic BAT by leptin appears to be independent of the melanocortin system.
Hypertension 1999 Jan
PMID:Interactions between the melanocortin system and leptin in control of sympathetic nerve traffic. 993 Nov 62

Primary empty sella syndrome (ESS) is an anatomo-radiological picture characterized by the presence of an arachnoid herniation filled with liquor that compresses the pituitary against the sellar wall. ESS occurs particularly in obese, hypertensive, cephalgic women, it is often asymptomatic but it may be associated with ophthalmologic, neurologic and sometime non-characterizing endocrine disorders. We report here 71 cases of primary ESS observed and assessed during the last fourteen years. The following endocrinological diagnostic procedures were carried out: hormonal (RIA) basal profile: FT3, FT4, TSH, PRL, ACTH, FSH, LH, 8.00 a.m. and p.m. cortisolemia, Aldo, PRA, DHEA-S, FTe, E2, P, PTH, CT, and calcemia and phosphoremia; provocative tests: TRH, GnRH, insulin hypoglycemia, etc.; inhibition tests: "overnight" and high dose dexamethasone. Clinical, radiological (skull radiographs, CT and/or MRI) and ophthalmologic (fundus, visual fields) assessment were made. We found principally cephalgia (52/71: 73.2%), hypertension (42/71: 59.1%), obesity (47/71: 66.1%). But we found especially mental disorders (57/71: 80.2%), in our knowledge not previously reported in the literature, as anxiety or dysthymic disorders with behavioural disturbances (chiefly oral compulsion). We found endocrinopathies in 36/71 (50.7%), isolated or coexisting in some patients: hyperPRL (14%), hypopituitarism (10.4%), hypogonadism (7%), diabetes insipidus (2.8%), hyperACTH (1.4%), hypoGH (15.4%), pituitary adenomas (8.4%). Several hypothalamic illness show a clinical picture including mental disorders and obesity. The Authors hypothesize that the ESS may be a "new" hypothalamic syndrome (compression/stretching on hypophysis and/or hypophyseal stalk by arachnoidocele; disorder of some hormones and neurotransmitters as leptin, neuropeptide Y, orexins, POMC-derived peptides, etc).
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PMID:[Primary empty sella syndrome. Observations on 71 cases]. 1020 96

The adipocyte hormone, leptin, is secreted in proportion to adipose mass and is implicated in the regulation of energy balance via its central actions on food intake and sympathetic nervous system activity. The placenta was also shown recently to be a possible source of leptin in pregnant women, raising the possibility that the normal relationship between leptin and adiposity may be altered in pre-eclampsia. We therefore sought to assess the extent to which maternal second trimester serum leptin concentrations differed for women who would subsequently develop pre-eclampsia and those who would remain normotensive. This nested case-control study population comprised 38 women with pregnancy-induced hypertension and proteinuria (pre-eclampsia) and 192 normotensive women. Multiple least-squares regression procedures were used to assess the independent relationship between leptin concentrations and risk of pre-eclampsia. Serum leptin concentrations, measured by radioimmunoassay, were highly correlated with maternal pre-pregnancy and second trimester body mass index (r = 0.71 and r = 0.74 respectively; P < 0.001 for both) among normotensive women, and to a lesser extent among women who developed pre-eclampsia (r = 0.29 and r = 0.42; P = 0.09 and 0.02 respectively). Among women with a pre-pregnancy body mass index of < or = 25 kg/m2, pre-eclampsia cases compared with controls had higher mean second trimester leptin concentrations after adjustment for confounding factors. In contrast, pre-eclampsia cases had lower mean leptin concentrations than controls for those women with a pre-pregnancy body mass index above 25 kg/m2. Other factors in addition to the level of adiposity may therefore influence serum leptin concentrations in pre-eclamptic pregnant women. Our results suggest the possibility that leptin, like several other placentally derived substances (e.g. steroid hormones, eicosanoids and cytokines), may be involved in the pathogenesis of pre-eclampsia. Further work is needed to confirm our findings and to assess the metabolic importance and determinants of leptin concentrations in uncomplicated and pre-eclamptic pregnancies.
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PMID:Pre-eclampsia disrupts the normal relationship between serum leptin concentrations and adiposity in pregnant women. 1021 9

This cross-sectional study aimed to evaluate the relationship between leptin and the cluster of abnormalities often referred to as the metabolic syndrome. The serum leptin concentration, body mass index (BMI), percent body fat, total fat mass (FM), waist and hip circumference, waist to hip ratio (WHR), prevalence of hypertension, and triglyceride (TG), lipoprotein, and uric acid concentration were determined in 86 type 2 diabetic (n = 59) and healthy (n = 27) subjects. Multiple regression analyses showed that the estimates of total body obesity (BMI, percent body fat, and total FM), sex, and serum uric acid concentration are independently associated with the serum leptin concentration. The finding of a positive correlation between serum leptin and uric acid levels suggests that leptin could be a pathogenic factor responsible for hyperuricemia in obesity.
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PMID:Serum leptin is associated with serum uric acid concentrations in humans. 1038 Nov 38

Obesity poses a serious health hazard and its treatment is often disappointing. Major advances have been made during recent years in the understanding of body weight regulation, with the discovery of leptin, a protein produced by adipocytes and acting on the central nervous system to reduce food intake, and that of beta-3 adrenergic receptors and uncoupling proteins which contribute to stimulate energy expenditure. Numerous metabolic complications are associated with abdominal obesity and most of them, such as diabetes mellitus, dyslipidaemias and arterial hypertension, appear to be linked to insulin resistance and may be part of the socalled metabolic syndrome or syndrome X. While very-low-calorie diets are usually effective in the short-term, they cannot, in the long-term and for most patients, solve the problem of severe obesity. Pharmacological antiobesity treatment may include drugs that reduce food intake, drugs that increase energy expenditure and drugs that affect nutrient partitioning or metabolism. All of these pharmacological approaches have potential efficacy, but unfortunately serious limitations. This is also the case of mechanical means, such as intragastric balloons. Consequently, bariatric surgery may be considered as a valuable alternative therapy in well-selected patients with morbid obesity refractory to classical treatments. In conclusion, obesity is a chronic disease and should be treated as such with reasonable expectations.
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PMID:Medical aspects of obesity. 1042 50

Previous studies demonstrated elevated plasma leptin and angiotensinogen (PRA) levels in essential hypertension. However, a few studies investigated the relationship between leptin and angiotensinogen levels in both lean and overweight/ obese hypertensives. The aim of the present study was therefore to examine the relationship between blood pressure, leptin and plasma renin activity in normotensives and in both lean and overweight/obese patients with essential hypertension. Two groups of subjects who were carefully matched for age, gender, waist:hip ratio and body mass index (BMI) were studied: 28 normotensives (NT) (age: 40.1+/-9.1 years old, BMI: 28.1+/-3.6 kg/m2, male/female: 18/10) and 33 newly diagnosed mild to moderate essential hypertensives (EHT) (age: 38.9+/-10 years old, BMI: 27.9+/-4.8 kg/m2, male/female: 22/11). No significant differences in age, gender, waist:hip ratio, fasting blood glucose and BMI were detected between EHT and NT groups. However, systolic and diastolic pressures, mean arterial blood pressures, plasma leptin levels and PRA were significantly higher in EHT group than in NT group (P = 0.001). Plasma leptin levels were strongly correlated with BMI in EHT (r=0.67, P = 0.001) and NT groups (r=0.44, P = 0.001). Plasma leptin levels were correlated with plasma PRA levels in both EHT and NT groups (r = 0.66 and r = 0.44; both P < 0.05, respectively). There was no correlation between leptin or PRA and systolic, diastolic pressures, or mean arterial blood pressures. Furthermore, the patients were divided as lean (n=16) and overweight/obese (n = 17) and compared with BMI-matched controls. In both subgroups, plasma leptin and PRA levels were also higher than those of controls. Our results showed that elevated plasma leptin and PRA are associated with hypertension in both lean and overweight/obese hypertensives. Moreover, plasma leptin was significantly correlated with plasma angiotensinogen levels. These findings suggest that adipose mass is an important determinant of blood pressure, although the mechanism is not clear.
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PMID:Plasma leptin levels strongly correlate with plasma renin activity in patients with essential hypertension. 1045 Aug 36

Excess of body fat, or obesity, is a major health problem and confers a higher risk of cardiovascular and metabolic disorders such as diabetes, hypertension, and coronary heart disease. Leptin is an adipocyte-derived satiety factor that plays an important role in the regulation of energy homeostasis, and its synthesis and secretion are markedly increased in obese subjects. To explore the metabolic consequences of an increased amount of leptin on a long-term basis in vivo, we generated transgenic skinny mice with elevated plasma leptin concentrations comparable to those in obese subjects. Overexpression of leptin in the liver has resulted in complete disappearance of white and brown adipose tissue for a long period of time in mice. Transgenic skinny mice exhibit increased glucose metabolism accompanied by the activation of insulin signaling in the skeletal muscle and liver. They also show small-sized livers with a marked decrease in glycogen and lipid storage. The phenotypes are in striking contrast to those of recently reported animal models of lipoatrophic diabetes and patients with lipoatrophic diabetes with reduced amount of leptin. The present study provides evidence that leptin is an adipocyte-derived antidiabetic hormone in vivo and suggests its pathophysiologic and therapeutic implications in diabetes.
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PMID:Increased glucose metabolism and insulin sensitivity in transgenic skinny mice overexpressing leptin. 1048 Jun 14

Substantial evidence from epidemiological data supports a link between obesity and hypertension. However, the relationship between the two disorders is not straightforward and most likely represents an interaction of demographic, genetic, hormonal, renal, and hemodynamic factors. Age, race, and sex also modulate the strength of the association between obesity and hypertension. Hyperinsulinemia, which is characteristic of obesity, can contribute to the probability of developing hypertension by activating the sympathetic nervous system (SNS) and by causing sodium retention. The pressor effect of insulin in obesity may be further enhanced by the observation that its vasodilator action can be blunted in obese subjects. Preliminary data have shown that leptin, whose levels are increased in most obese individuals, can contribute to hypertension in obesity through its effects on insulin, SNS, and sodium excretion. The kidney may also have a role in the pathophysiology of hypertension in obesity. Abnormal renal sodium handling coupled with structural changes in the kidney of an obese patient can raise blood pressure. In addition, obesity is associated with distinct cardiovascular hemodynamic alterations and development of eccentric myocardial hypertrophy. Most of these obesity-associated abnormalities, as well as hypertension itself, can be reversed by weight loss. Furthermore, weight loss can prevent, or at least delay, the development of hypertension in patients with high-normal blood pressure. Weight reduction should be the first-line treatment in every obese hypertensive patient. However, the majority of patients will need pharmacologic intervention in conjunction with weight loss. Selection of antihypertensive agents in the overweight patient should take into account the mechanisms leading to hypertension and the metabolic abnormalities that characterize the obese patient.
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PMID:Obesity and hypertension. 1050 92

We have previously demonstrated that genetically based leptin deficiency due to a missense leptin gene mutation in a highly consanguineous extended Turkish pedigree is associated with morbid obesity and hypogonadism. We have now performed detailed assessments of endocrine, sympathetic, and immune function. We have also identified a new adult female homozygous patient in this extended family who is severely obese and amenorrheic. In this family all wild-type and heterozgous individuals have normal body weight. Seven obese members of this family, whom we presume to have been leptin deficient, died during childhood. There are several findings that indicate potentially novel targets for leptin action in humans. Four homozygous patients (1 adult male, 2 adult females, and 1 child) have sympathetic system dysfunction, whereas all heterozygous subjects have normal sympathetic system function. Despite sympathetic system dysfunction and postural hypotension, 1 of 3 homozygous adult patients has impaired renin-aldosterone function. The patients also exhibit alterations in GH and PTH-calcium function, and 1 of them has decreased bone mineral density. Despite their obesity, these patients do not have risk factors for cardiovascular disease, such as hypertension, impairments in lipid metabolism, or hyperleptinemia [corrected]. These data support the hypothesis that the obese may have central, but not peripheral, resistance to the effects of leptin and that hyperleptinemia [corrected] may mediate the cardiovascular morbidity of the obese who are not leptin deficient. Furthermore, these data indicate that there may be several new targets for leptin action in human physiology. Such new targets may lead to novel pharmacological strategies for the use of leptin agonists and antagonists in the treatment of human disease. All 19 normal weight individuals in this family are alive, whereas 7 of 11 obese individuals died in childhood after infections. The odds ratio for mortality in the context of this obesity phenotype is 25.4, indicating that this mutation severely impairs key biological functions during childhood, negatively impacting on survival. We found that only the obese child in this family had thyroid function abnormalities. The oldest homozygous female patient started to menstruate, albeit with a luteal phase defect, 7 months ago, after a delay of over 20 yr, whereas the younger adult subjects are still hypogonadic. Thus, we conclude that due to their long life span, humans who survive the negative effects of leptin deficiency during childhood can, in contrast to ob/ob mice, over decades compensate some of the effects of leptin deficiency on immunity and endocrine function through mechanisms that remain to be elucidated.
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PMID:Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. 1183 53

Intrarenal artery infusions of low-dose human, but not mouse, leptin cause diuresis/natriuresis in rats [E. K. Jackson and P. Li. Am. J. Physiol. 272 (Renal Physiol. 41): F333-F338, 1997]. The lack of effect of mouse leptin in the rat could be due to slight differences in the primary structure of mouse vs. rat leptin. To test this hypothesis, we infused single doses of rat (0.1, 0.3, 1, or 3 microgram/min) or human (3 microgram/min) leptin into the renal artery of rats for 140 min while continuously measuring blood pressure and the renal excretion rate of urine and electrolytes. Intrarenal infusions of rat leptin did not alter any measured parameter. Human leptin caused a delayed diuresis/natriuresis (P < 0.0006 and P < 0.0049, respectively) that required approximately 2 h to achieve a maximum effect and that was not accompanied by changes in blood pressure or potassium excretion. We conclude that low-dose human, but not low-dose rodent, leptin has direct diuretic/natriuretic activity. Our results can be explained from an evolutionary perspective, since obesity-induced hypertension would be a much greater selective force in hominids compared with rodents.
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PMID:A comparison of the natriuretic/diuretic effects of rat vs. human leptin in the rat. 1056 40


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