Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Several mechanisms have been implicated in the association between obesity and hypertension, including salt-sensitivity, insulin resistance and sympathetic activation. Obese animals and humans exhibit exaggerated blood pressure responses to increases in salt intake. 2. Although insulin resistance is common in obesity, it is clear that abnormal insulin action is not the sole or sufficient cause of hypertension in obesity. Obesity is associated with increased activity of the sympathetic nervous system. Sympathetic blockade has been reported to attenuate sodium retention and hypertension in experimental models of obesity. 3. The mediators responsible for salt sensitivity, insulin resistance and sympathetic activation in obesity remain unclear. 4. The novel protein hormone leptin is produced almost exclusively by adipose tissue and acts in the central nervous system through a specific receptor and multiple neuropeptide pathways to decrease appetite and increase energy expenditure. 5. Increasing evidence suggests that leptin may have wider actions influencing autonomic, cardiovascular, renal and endocrine function. We have shown that leptin increases sympathetic nerve activity to kidney, hindlimb and adrenal gland, in addition to brown adipose tissue. 6. Despite this sympathoexcitatory action, acute systemic administration of leptin does not acutely increase arterial pressure or heart rate in anaesthetized animals. This may reflect opposing antihypertensive actions of leptin. For example, leptin increases renal sodium and water excretion, apparently through a direct tubular action. In addition, leptin increases systemic insulin sensitivity, even in the absence of weight loss. 7. In conclusion, leptin may act as a mediator linking body adiposity with changes in insulin action, sympathetic neural outflow and renal sodium excretion. Alterations in leptin generation or action may, in part, underlie the sympathetic, endocrine and renal consequences of obesity.
 ...
PMID:Cardiovascular consequences of obesity: role of leptin. 949 62

Increased body mass index (BMI) has been correlated with increased blood pressure in human populations. To examine the role of the leptin gene (OB) in essential hypertension in African Americans, we performed affected sib pair analysis on a set of 103 hypertensive African American sibships using four highly polymorphic markers at the human leptin locus. No evidence of linkage was detected between these markers and the phenotype of essential hypertension either in these sibships or in a severely obese subset of 46 sibships in which each sibling had a BMI > or = 85th percentile for the US population. Using BMI rather than hypertension as a quantitative trait, we found significant linkage for the marker D7S504 (P=0.029) but not for the other markers. Significance strengthened in the overweight subset of sibships for this marker (P=0.001), and there was a trend of lower P values for the other three markers. However, multipoint analysis with the use of all four markers simultaneously to estimate linkage between BMI and the leptin locus did not demonstrate a statistically significant relationship. Analysis of the coding region of the leptin gene (exons 2 and 3) by single-strand conformational polymorphism revealed a rare Ile-Val polymorphism at amino acid 45 but revealed no other alterations. These results suggest that the OB gene is not a major contributor to the phenotype of essential hypertension in African Americans, although a minor contribution to the phenotype of extreme obesity in this group cannot be ruled out.
Hypertension 1998 Jun
PMID:Genetic markers at the leptin (OB) locus are not significantly linked to hypertension in African Americans. 962 34

Preeclampsia (PE) is a hypertensive disorder, which develops in late pregnancy and is usually associated with placental hypoxia and dysfunction. We have recently demonstrated that leptin is a novel placenta-derived hormone in humans and suggested its significance in human pregnancy (see Ref. 19). To explore the changes in the leptin production in placenta in PE, we measured the plasma leptin level and placental leptin messenger RNA expression in pregnant women with PE. Plasma leptin levels in preeclamptic women were elevated significantly, compared with gestational age- and body mass index-matched normal pregnant women (P < 0.0001). Plasma leptin levels in the severe PE group were significantly higher than those in the mild PE group (P < 0.0001). Plasma leptin levels in preeclamptic women were reduced, soon after the placental delivery, to those expected for their body mass indices. Northern blot analysis revealed that leptin messenger RNA levels are increased in the placentas from preeclamptic women, compared with normal pregnant women. Leptin secretion was increased significantly in a human trophoblastic cell line (BeWo cells) cultured under hypoxic conditions (5% O2), compared with those cultured under standard conditions (20% O2; P < 0.01). The present study demonstrated that placental production of leptin is augmented in severe PE, probably because of placental hypoxia, thereby suggesting the possible significance of leptin as a marker of placental hypoxia in severe PE.
 ...
PMID:Augmented placental production of leptin in preeclampsia: possible involvement of placental hypoxia. 974 32

Obesity, a common multifactorial disorder, is a major risk factor for type 2 diabetes, hypertension and coronary heart disease (CHD). According to the definition of the World Health Organization (WHO), approximately 6-10% of the population in Westernized countries are considered obese. Epidemiological studies have shown that 30-70% of the variation in body weight may be attributable to genetic factors. To date, two genome-wide scans using different obesity-related quantitative traits have provided candidate regions for obesity. We have undertaken a genome-wide scan in affected sibpairs to identify chromosomal regions linked to obesity in a collection of French families. Model-free multipoint linkage analyses revealed evidence for linkage to a region on chromosome 10p (MLS=4.85). Two further loci on chromosomes 5cen-q and 2p showed suggestive evidence for linkage of serum leptin levels in a genome-wide context. The peak on chromosome 2 coincided with the region containing the gene (POMC) encoding pro-opiomelanocortin, a locus previously linked to leptin levels and fat mass in a Mexican-American population and shown to be mutated in obese humans. Our results suggest that there is a major gene on chromosome 10p implicated in the development of human obesity, and the existence of two further loci influencing leptin levels.
 ...
PMID:A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10. 980 54

Leptin levels in subjects with android obesity with the insulin resistance syndrome (syndrome X, 5H) are in general elevated, as compared with non-obese subjects and correlate with the BMI, with the percentage of body fat, WHR, IRI levels and sex (they are higher in women), as it is the case in the general population. In the elevated leptin level in syndrome 5H (association of hyperinsulinism, hyperglycaemia-NIDDM, hyperlipoproteinaemia with android obesity, arterial hypertension and hirsutism in females with the polycystic ovaries syndrome) participate in a significant way also elevated basal IRI and cortisol levels as well as an elevated postprandial IRI response during oGTT despite the fact that leptin and endothelin-1 levels do not rise significantly during oGTT despite hyperinsulinaemia. Leptin levels were however higher in men (liminally significant in women) with an hyperinsulinaemic response during oGTT, as compared with probands with a normal insulin response. Optimal insulin and glucocorticoid levels are the prerequisite for a rise of leptin because proadipocytes in vitro begin to produce leptin as soon as insulin is added to the medium and this effect is trebled, if cortisol is added. It appears that the insulin and leptin resistance in syndrome 5H are parallel phenomena which potentiate each other. Elevated insulin and cortisol levels maintain elevated leptin levels which in turn enhances the insulin resistance in muscles and at the same time has an impact on the IRI response to postprandial hyperglycaemia. In the background of this insulin and leptin resistance in the majority of subjects with the 5H syndrome there is apparently no actual molecular defect of the hormone and its receptors in target tissues but a possible defect in mechanisms of postreceptor transduction of the hormonal signal. In the hormonal resistance participate moreover also two general and non-specific mechanisms such as: 1. increased consumption or uptake of hormonal receptors by elevated levels of the appropriate hormone ("down regulation" phenomenon), 2. disorders of paracrine endothelial mechanisms of the vascular wall which determine via the control of the inflow in the regional microcirculation the availability of insulin, leptin and metabolic substrates to target tissues. Impaired vasodilatation reserves and the development of paradoxical vascular spasms in response to stimuli which normally cause vasodilatation (strain, administration of acetylcholine, histamine, ATP etc.) are constant, associated phenomena in hyperlipoproteinaemias, arterial hypertension and in type 2 diabetics. These phenomena are the syndrome of insulin resistance and syndrome 5H-X resp. Endothelin-1 levels assessed in the systemic circulation are however due to their short biological half-life and the paracrine action of endothelin-1 not sensitive markers of endothelial dysfunction in syndrome X.
 ...
PMID:[Relation between levels of leptin, insulin and cortisol in persons with the 5H (X) syndrome]. 982 79

In this study we wanted to evaluate the relationship between the ob gene product leptin and blood pressure, as well as plasma renin activity and plasma aldosterone levels. We studied 139 subjects with a mean+/-SD age of 50 +/-14 years and a body mass index of 26.5+/-5.3 kg/m2; 110 subjects had essential hypertension and 29 were healthy nonhypertensive controls. Blood pressure was measured in resting conditions in the morning and blood was drawn for the determination of the plasma renin activity, aldosterone, and leptin levels. The mean blood pressure of the population was 155/97 mm Hg. The relationship between these parameters was studied by univariate regression analysis according to gender and, whenever indicated, adjusted for age and body mass. The mean+/-SEM plasma leptin level in the whole population was 9.5+/-0.6 ng/mL (range, 1.1-43.3). Subjects with stage I hypertension had significantly higher plasma leptin levels than normotensive subjects. Systolic blood pressure correlated with the plasma leptin levels and the leptin levels adjusted for body weight in women (r = 0.422, P < .01) and nonhypertensive men (r = 0.644, P = .03) only. Plasma renin activity (r = 0.329, P = .03) and aldosterone levels (r = 0.342, P = .026) correlated with the leptin concentration. A significant relationship between the peripheral expression of the ob gene product leptin and systolic blood pressure was found in women and nonhypertensive men. In view of the multiple functions of leptin a causal relationship is postulated and potential mechanisms may involve modulatory effects of leptin on neuropeptide Y, angiotensinogen gene expression, the modulation of the autonomous nervous system, or effects on the pituitary adrenal axis. Direct relationships between both plasma renin activity and aldosterone levels and leptin support the potential importance of the relationship between leptin and blood pressure. Our observation may be of future importance for the understanding of the link between the increase in blood pressure and increasing body weight.
 ...
PMID:Is there a role for the ob gene product leptin in essential hypertension? 983 73

The hemodynamic, hormonal, and renal excretory effects of intravenous bolus administration of synthetic murine leptin were examined in groups of anesthetized normotensive (Sprague-Dawley), hypertensive (spontaneously hypertensive), and both lean and obese Zucker rats. In the normotensive animals (n = 8) an intravenous bolus of 400 microgram/kg of leptin produced a significant six- to sevenfold elevation in sodium excretion compared with controls (n = 8). The onset of natriuresis was delayed for approximately 30-45 min. Mean arterial pressure (MAP), creatinine clearance, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) remained unchanged. In contrast, the hypertensive rats were refractory to the natriuretic effects of leptin when infused either with 400 (n = 8) or 1,600 (n = 8) microgram/kg. Also in these animals MAP, creatinine clearance, PRA, and PAC were unmodified. Finally, whereas lean Zucker rats (n = 8) responded very similarly to the Sprague-Dawley animals, the natriuretic effect of the hormone was attenuated in the obese Zucker groups. At 400 microgram/kg (n = 8) no natriuresis was elicited, but at 1,600 microgram/kg (n = 8) a modest but significant two- to threefold increment in sodium excretion was observed in the obese rats. In both Zucker groups, MAP, creatinine clearance, PRA, and PAC were unchanged. Collectively, these results demonstrate a significant natriuretic effect of exogenous leptin in the normal rat and a blunted saluretic response in hypertension and obesity. It is suggested that leptin may be a potential salt-excretory factor in normal rats and may function pathophysiologically in obesity and hypertension.
 ...
PMID:Renal effects of leptin in normotensive, hypertensive, and obese rats. 984 97

The present review discusses recent research showing adipose tissue to be highly metabolically active, producing and releasing many different bioactive compounds besides free fatty acids (FFA) such as tumor necrosis factor alpha (TNF alpha), leptin, acetylation stimulating protein (ASP), plasminogen activator inhibitor-1 (PAI-1), cholesterol ester transfer protein (CETP), prostaglandins and oestrogens. Most of these compounds have autocrine effects on the adipose cells and they are presumably involved in the physiological regulation of blood flow, growth and metabolism of the adipose tissue. When the adipose tissue becomes enlarged, as seen in association with obesity, it has now been shown that several of the compounds produced in the adipose tissue (TNF, PAI-1, CETP etc.) may be directly involved in the pathogenesis of some of the complications commonly seen in association with obesity such as insulin resistance, hypertension, enhanced thrombogenesis, and premature atherosclerosis.
 ...
PMID:[The auto- and endocrine function of the adipose tissue. Significance for metabolic complications in obesity]. 985 22

While the hyperleptinemia of obesity is likely to be associated with the metabolic complications of obesity/hyperinsulinemia/insulin resistance, it is not associated with diabetes, with the relative hypercortisolism of upper body obesity, with hypertension in women, (it is in men), or with dyslipidemia. Overall, the correlations between leptin and the metabolic diseases associated with obesity are weak. The equivocal results of an association of leptin with components of the metabolic syndrome make it unlikely that leptin affects these directly. (On the other hand, these correlations, when found, preclude any causal relationship between leptin and metabolic diseases.) There are experimental data showing a definite role for insulin and glucocorticoids in the regulation of leptin, and of leptin in the regulation of insulin. More data are required on the effects of leptin, but it is likely that leptin will not be a major link between obesity and the metabolic syndrome. Certainly, however, when leptin is available for clinical use, its effect on different aspects of the metabolic syndrome will be worth studying.
 ...
PMID:Therapeutic controversy: Obesity--a modern-day epidemic. 992 54

offsity is associated with an increased risk of hypertension. In the past 5 years there have been dramatic advances into the genetic and neurobiological mechanisms of obesity with the discovery of leptin and novel neuropeptide pathways regulating appetite and metabolism. In this brief review, we argue that these mounting advances into the neurobiology of obesity have and will continue to provide new insights into the regulation of arterial pressure in obesity. We focus our comments on the sympathetic, vascular, and renal mechanisms of leptin and melanocortin receptor agonists and on the regulation of arterial pressure in rodent models of genetic obesity. We suggest 3 concepts. First, the effect of obesity on blood pressure may depend critically on the genetic-neurobiological mechanisms underlying the obesity. Second, obesity is not consistently associated with increased blood pressure, at least in rodent models. Third, the blood pressure response to obesity may be critically influenced by modifying alleles in the genetic background.
Hypertension 1999 Jan
PMID:State-of-the-art-lecture: Obesity-induced hypertension: new concepts from the emerging biology of obesity. 993 Nov 61


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>