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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin-1 (ET-1) is a potent and long-lasting vasoconstrictor peptide. In order to clarify the changes in the level of ET-1 with aging, we measured the ET-1 level in plasma by radioimmunoassay and used 74 healthy subjects including 61 males and 13 females, aged from 30 to 69, who were admitted in the health check center of Ashikaga Red Cross Hospital. None of them had risk factors related to hypertension, obesity, diabetes mellitus or cardiovascular disease. In the male group, the relationship between the level of ET-1 (Y) and age (X) was obtained as follows: Y = 0.08857 X +0.06363. The correlation between them was significant (gamma = 0.65894, p < 0.05). In the female group also, the increased level of ET-1 (Y) with age (X) showed an excellent linear relationship (Y = 0.163091 X -4.23, gamma = 0.762, p < 0.002). These studies demonstrated that the level of ET-1 increased in relation to aging and the increased ET-1 production with aging may be consistent with deterioration of endothelial function.
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PMID:[Changes in the level of endothelin-1 with aging]. 855 91

Endothelin-1 (ET-1) exerts powerful vasoconstrictive and blood pressure elevating properties through endothelial cells. However, no systematic examination of ET-1 in migraine has ever been attempted. The present investigation was focused on evaluating the level of ET-1 in patients with migraine with aura. Studies on ET-1 were made in 17 patients with migraine with aura (age, 23.4 +/- 9.1 years old, mean +/- SD) according to the Classification of Headache of the Ad Hoc Committee. All patients had been free of migraine attacks for at least 7 days prior to the examination. Twenty-eight age-matched healthy volunteers (age, 23.0 +/- 12.3 years old) were similarly used as a control group. None of them revealed evidence of any other disease, such as hypertension, obesity, or heart disease. Informed consent was obtained from each subject. We measured the immunoreactive ET-1 in plasma by radioimmunoassay. The plasma level of ET-1 in migraine was 2.53 +/- 1.06 pg/ml. On the other hand, the level of ET-1 in the controls was 4.24 +/- 0.80 pg/ml. The ET-1 level in migraine was significantly lower than that in the controls (p < 0.002). We also measured the level of ET-1 in the cerebrospinal fluid (CSF). There was no significant difference between migraine (23.2 +/- 3.10 pg/ml) and the control group (20.85 +/- 3.20 pg/ml). In conclusion, the lower plasma level of ET-1 observed in the patients with migraine is consistent with the pathogenesis of migraine, further supporting the hypothesis that a lower ET-1 may be closely related to marked vasodilatation following constriction partly due to a deficiency of ET-1 for maintaining vasoconstriction.
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PMID:[Lower level of endothelin-1 in migraine with aura]. 872 Mar 38

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.
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PMID:[Relation between levels of leptin, insulin and cortisol in persons with the 5H (X) syndrome]. 982 79

Endothelin-1, released from the vascular endothelium after cleavage from big endothelin-1, is a potent paracrine vasoconstrictor peptide. Small studies suggest that circulating levels of endothelin-1 are elevated in subjects with cardiovascular risk factors. Big endothelin-1 levels may better reflect endothelin-1 generation. We examined relationships between plasma endothelin-1, plasma big endothelin-1, and predisposition to hypertension or other cardiovascular risk factors associated with insulin resistance in a large group of healthy young men. We recruited 96 healthy men aged 24-33 years from a cohort of 864 young men and women in whom predisposition to hypertension had been defined on the basis of their own blood pressure and the blood pressures of their parents. They attended after an overnight fast for measurement of blood pressure, anthropometry, and plasma lipids, insulin, glucose, endothelin-1 and big endothelin-1. Plasma endothelin-1 and big endothelin-1 levels did not correlate with blood pressure (r=0.09, -0.002 respectively) and were not influenced by parental blood pressure. Higher plasma endothelin-1 levels were associated with higher body mass index (r=0.29, p<0.005), and higher plasma insulin (r=0.21, p<0.05). Higher plasma big endothelin-1 levels were associated with insulin resistance, as assessed by the Homeostasis Model of Assessment resistance index (r=0.30, p<0.005). Endothelin-1 levels are not related to blood pressure, but are higher in healthy young men with insulin resistance and obesity.
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PMID:Activation of the endothelin system in insulin resistance. 1139 Oct 30

The endothelium produces a variety of substances that play important roles in regulation of the circulation and vascular wall homeostasis. The control of blood vessel wall homeostasis is achieved via production of vasorelaxants and vasoconstrictors. Among the vasorelaxants are nitric oxide (NO), prostacyclin, various endothelium-derived hyperpolarizing factors (EDHFs, such as cytochrome P-450 monooxygenase metabolites of arachidonic acid like epoxyeicosatrienoic acids, and endocannabinoids), and C-type natriuretic peptide. Among the vasoconstrictors we find endothelin-1 (ET-1) and endothelium-derived contracting factors (EDCF) that are cyclooxygenase products such as endoperoxides and thromboxanes. The endothelium, via these and other agents, also exerts a critical influence on the blood stream, particularly formed elements such as leucocytes and platelets, and on substances involved in blood coagulation. All these effects contribute to modulating the growth of the vascular wall in hypertension, and participate in the development of atherothrombotic complications associated with hypertension. Inhibition of NO production may induce elevation of blood pressure in experimental animals. However, even today, we do not have incontrovertible evidence of participation of NO, EDHFs or EDCFs, or other endothelial products, in the pathogenesis of hypertension, although there is evidence of abnormal endothelium-dependent relaxation in hypertension in many but not all hypertensives. It is unclear, however, to what extent this may precede hypertension or be a consequence of elevated blood pressure, possibly contributing to its complications. Also, it is often difficult to dissociate abnormal endothelium-dependent relaxation from confounding factors such as the presence of associated conditions like dyslipidaemia, diabetes, smoking, obesity, hyperhomocysteinaemia, and others, that are accompanied themselves by abnormal endothelium-dependent relaxation. There is some evidence for a role of ET-1 in blood pressure elevation in some experimental forms of hypertension, particularly severe, sodium-sensitive hypertension, in which it may play a role in accentuating rather than initiating blood pressure elevation. Endothelin-1 may play a similar role in human hypertension.
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PMID:A critical review of the role of endothelial factors in the pathogenesis of hypertension. 1181 73

Resistin is an adipocyte-derived hormone whose role in the development of insulin resistance is controversial. Endothelin-1 (ET-1) is a 21 amino acid peptide demonstrated to possess vasoconstrictor, positive inotropic, mitogenic, and metabolic properties. In numerous disease states, including congestive heart failure, obesity, and diabetes, elevated levels of ET-1 have been reported and are thought to contribute to the pathology of the disease. A recent study demonstrated that ET-1 induces the expression and stimulates the secretion of the adipose tissue-derived hormone leptin. However, the effect of ET-1 on resistin secretion has not been determined. To characterize the effect of ET-1 on resistin secretion, 3T3-L1 fibroblasts were differentiated into adipocytes and allowed to mature for 14 days. Cells were incubated for 24h with ET-1 (1-100 nM), insulin (1-100 nM), insulin+ET-1 (100 nM I+E) or the appropriate vehicle or antagonist. At the end of the incubation period, resistin secretion was determined in the media by immunoblotting and densitometric analysis. ET-1 (1-100 nM) significantly decreased basal resistin secretion by 49% (1 nM), 43% (10nM), and 59% (100 nM). Insulin (1-100 nM) produced a concentration-dependent increase in resistin secretion from 3T3-L1 adipocytes (1 nM-42%, 10nM-55%, and 100 nM-86% vs. control). Insulin-stimulated resistin secretion (100 nM) was almost completely inhibited (94%) by ET-1 (100 nM). The effects of ET-1 on resistin protein secretion were inhibited by co-incubation with the ET(A) receptor antagonist BQ-610. In conclusion, our studies demonstrate that basal and hormonal stimulation of resistin secretion by insulin are inhibited by ET-1. Such findings demonstrate that resistin secretion is regulated in a similar manner to other adipose tissue factors, including leptin, in 3T3-L1 adipocytes. In addition, our findings suggest that vascular factors such as ET-1 may regulate whole body energy metabolism through adipocyte-derived hormones, including leptin and resistin.
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PMID:Endothelin-1 inhibits resistin secretion in 3T3-L1 adipocytes. 1216 29

Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide produced by endothelial and smooth muscle cells. Many lines of biological evidence suggest that the ET-1 gene is a candidate gene for hypertension. Moreover, recent association studies suggested that a G/T polymorphism with an amino acid substitution (Lys/Asn) at codon 198 in exon 5 of the ET-1 gene interacts with body mass index (BMI) in association with blood pressure. They suggested that T carriers are more sensitive to weight gain than GG homozygotes in association with blood pressure. However, association studies are often irreproducible, and the first study often suggests a stronger genetic effect than is found by subsequent studies. We therefore assessed the interaction in 2 large Japanese populations. The present study showed a nonsignificant but similar trend to the results of previous reports. Moreover, in line with previous reports, this study revealed a significant interaction between the ET-1 K198N (G/T) polymorphism and BMI in association with hypertension in our populations (P=0.027). The interaction was significant, even after adjustment for gender and age (P=0.045) and for all confounding factors (P=0.044). T carriers were more sensitive to weight gain than GG homozygotes in association with hypertension. Considering the combined impact of obesity and hypertension on the development of cardiovascular and cerebrovascular disorders, T allele carriers might represent elective targets for therapy to lower their body weight.
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PMID:Association of endothelin-1 gene variant with hypertension. 1251 47

Endothelin-1 (ET-1) is a pleiotropic hormone produced primarily by the endothelium. Synthesis of ET-1 is stimulated by the major signals of cardiovascular stress, such as vasoactive agents (angiotensin II, norepinephrine, vasopressin, and bradykinin), cytokines (e.g., tumor necrosis factor alpha and transforming growth factor beta), and other factors, including thrombin and mechanical stress. ET-1 induces vasoconstriction, is proinflammatory, promotes fibrosis, and has mitogenic potential, important factors in the regulation of vascular tone, arterial remodeling, and vascular injury. These effects are mediated via two receptor types, ETA and ETB. The role ET-1 plays in normal cardiovascular homeostasis and in mild essential hypertension in humans is unclear. However, certain groups of essential hypertensive patients may have ET-1-dependent hypertension, including blacks (subjects of African descent), salt-sensitive hypertensives, patients with low renin hypertension, and those with obesity and insulin resistance. ET-1 has also been implicated in severe hypertension, heart failure, atherosclerosis, and pulmonary hypertension. In all of these conditions, plasma immunoreactive ET levels are elevated and tissue ET-1 expression is increased. Accordingly, it is becoming increasingly apparent that ET-1 plays an important role in cardiovascular disease and in some forms of hypertension in humans. Data from clinical trials using combined ETA-ETB receptor blockers have already demonstrated significant blood-pressure-lowering effects. Thus, targeting the endothelin system may have important therapeutic potential in the treatment of hypertension, particularly by contributing to the prevention of target organ damage and the management of cardiovascular disease.
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PMID:Role of endothelin in human hypertension. 1283 65

Adiponectin is an adipocyte-derived hormone best known for its insulin-sensitizing ability. The expression and circulating concentration of adiponectin are decreased in type 2 diabetics and increase following treatment with thiazolidinediones. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide whose levels are elevated in numerous disease states, including obesity and diabetes. ET-1 has profound effects on adipose tissue metabolism and alters the release of adipose-derived factors such as leptin and resistin, therefore we investigated the role of ET-1 in adiponectin secretion. 3T3-L1 adipocytes were treated with insulin (100 nM), ET-1 (100 nM), or the appropriate vehicle and adiponectin secretion into the media was determined by immunoblotting and densitometric analysis. Adiponectin secretion significantly increased 1h following insulin or ET-1 treatment, respectively. Pretreatment with ET-1 for 24h significantly inhibited the ability of insulin or ET-1 to acutely stimulate adiponectin secretion. The specific ET(A) receptor antagonist, BQ-610 (1 microM), significantly inhibited ET-1-stimulated adiponectin secretion. In summary, ET-1 acutely stimulates adiponectin secretion through the ET(A) receptor. Chronic exposure to ET-1 dramatically decreases the stimulatory effect of insulin and ET-1 on adiponectin secretion. Our findings suggest vascular factors such as ET-1 may play a role in the regulation of adiponectin secretion and whole body energy metabolism.
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PMID:Regulation of adiponectin secretion by endothelin-1. 1465 62

Endothelial dysfunction has been suggested to play an important role in the development of obesity-induced hypertension. Because endothelin release increases in response to endothelial damage, we examined whether endothelin-1 contributes to increased arterial pressure in a model of visceral obesity produced by feeding Sprague-Dawley rats a high-fat (HF) diet (40% fat w/w, n=6) for 12 months. Arterial and venous catheters were implanted for measurement of mean arterial pressure (MAP) and heart rate (HR) 24 hours per day and intravenous infusions. After a 5-day control period, rats were infused with the selective endothelin-1 type A receptor (ET-A) blocker ABT-627 (2.5 mg/kg per day, IV) for 9 days, followed by a recovery period. Rats fed a standard chow (normal fat, or NF, group: n=6) for 12 months were also infused with ET-A blocker and were used as controls. Compared with NF rats, HF rats had higher MAP (113+/-4 versus 98+/-2 mm Hg), increased visceral fat (18.7+/-2.0 versus 10.8+/-1.4 g), and 3.2-fold increase in plasma leptin despite similar total body weight gain. Long-term ET-A blockade markedly reduced MAP in HF (-14+/-3 mm Hg) and NF (-14+/-2 mm Hg), but it had no effect on HR, GFR, or PRA. These results indicate that a long-term HF diet may cause visceral obesity and increased MAP, even in the absence of major changes in total body weight. Endothelin-1 appears to play an important role in the maintenance of arterial pressure in rats fed HF and NF diets, but it does not appear to contribute to increased MAP in this model of diet-induced hypertension.
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PMID:Role of endothelin-1 in blood pressure regulation in a rat model of visceral obesity and hypertension. 1470 64


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