UMLS:C0028754 - FACTA Search

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Query: UMLS:C0028754 (obesity)
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Angiotensin II exerts its action via at least two distinct receptor subtypes designated AT1 and AT2. AT1 receptors seem to be responsible for most of the known angiotensin II effects while the role of AT2 receptors is not yet clear. Adipocytes of adult rats express exclusively the AT1 subtype. Angiotensin II stimulates prostacyclin release in adult rat adipocytes and in mouse preadipocytes. In the latter prostacyclin release is completely blocked by an AT2 receptor antagonist. Adipocyte angiotensin II receptors seem to be regulated by age and fat mass. Blockade of these receptors by an AT1 antagonist seems to prevent adipose tissue hypertrophy. Moreover, adipose tissue contains all the main components of the renin-angiotensin system such as angiotensinogen, angiotensin converting enzyme, angiotensin II and angiotensin II receptors. Angiotensinogen expression in adipocytes is stimulated by a high fat diet concurrent with enlargement of fat mass, associated with insulin resistance. Angiotensin converting enzyme inhibitors improve insulin sensitivity. Taken together, there is evidence of interaction between insulin and angiotensin II in regulation of adipose tissue metabolism and cellularity. Clarification of these interactions could lead to significant progress in pharmacological treatment of obesity and its comorbidity.
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PMID:The role of angiotensin II and its receptors in regulation of adipose tissue metabolism and cellularity. 878 38

The risk factors of stroke in young adults and in the whole population are the same in general, but there are some special risk factors in young adults. They are congenital or early acquired diseases which are complicating with early stroke. We studied the risk factors of cerebrovascular insults in 150 patients, 20-49 years old (Table 1). This was 26.04 percent of all patients that were hospitally treated in the urgent neurological department over one year. However, twenty years ago, this percent was 20.20 [2]. We found that arterial hypertension was dominant both among young adults (47.99 percent) and in the whole population (Table 2) [1-3]. Essential hypertension was the most frequent, and renal and thyreotoxical hypertensions were rare. The atherogenic level of low density and high density lipoproteins (LDL/HDL) was present in 14.66 percent of young adult patients [3]. Diabetes mellitus, a known risk factor of stroke, was found in 5.33 percent of our studied patients, especially in the juvenile form [1-3]. Besides juvenile diabetes mellitus, we found other risk factors that were characteristic of young adults: systemic lupus erythematosus (3.33 percent), which began at an early vital age, and numerous cerebrovascular complications appeared during the first five years of illness [7]. In this group of young adults, we found no other type of vasculitis, which also can be a risk factor of stroke. Great risk factors of stroke in young adults were arterial-venous malformation, brain aneurysm and congenital muscular hypoplasia of the carotide and middle caliber cerebral arteries-multiple progressive intracranial arterial occlusion or Nishimoto Takeuchi disease or Moya Moya disease, which were found in 3.99 percent of our patients. These diseases were complicated by cerebrovascular haemorrhagic or ischaemic insults over the young vital period [9]. The similar was with congenital or early acquired (rheumatic fever) heart valve defects (3.99 percent in our group), with early cerebrovascular complications due to cardiogenic thromboembolism mechanisms [10]. In 2 percent of patients the stroke was the consequence of anticoagulant therapy. These were the patients with operated heart valve defects (haemodynamic risk factor was eliminated, but haemorrheological risk factor was evident) [2, 3]. Also, disturbances of cardiac rhythm were risk factors of stroke in 2 percent of our patients. The mechanism of stroke originated is cardiogenic thromboembolism or global hypotension and the following ischaemia in the border brain zone [11]. All these risk factors were present in a relatively small number of patients, but they were "strong" risk factors of stroke, especially in young adults. On the other hand, there were nicotinism, alcoholism and obesity. They were present in a greater percent (25.33; 15.66; 18.66 percent), but their influence was slow and indirect by haemorrheologic mechanism (the increasing aggregation of platelets, reduced flexibility of red and white blood cells, changed prostacycline-prostaglandin relation in endothelial and blood cells, viscosity of blood, LDL/HDL) [2, 3, 12, 13]. A prolonged psychogenic stress (8.66 percent in our group) was, also, a risk factor of stroke. It induced increase in catecholamine level, arterial hypertension, constriction of blood vessels, endothelial cell damages, increased aggregation of platelets, changed prostacycline-prostaglandin relation, metabolism of lipids and polysaccharides) [2, 3]. We found no abuse of ephedrine [16] or cocaine [15] as risk factors of stroke in our group, although it was described in litterature. Also, we found no postoperative thromboemolism (foramen ovale apertum). Ischaemic cerebrovascular insults dominated (77.34 percent) in our group of patients. In one article (Canada) [17] haemorrhagic insults were dominant in young adults. In our opinion, the number of our patients was not adequated, as haemorrhagic stroke is also treated in neurosurgical departments. The mor
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PMID:[Risk factors for stroke in young people]. 910 54

1. The obese fa/fa Zucker rat is a genetic model of obesity and insulin resistance which develops a number of metabolic and endocrine features of non-insulin-dependent diabetes, including hypertension, proteinuria and glomerular sclerosis. 2. We have investigated the urinary excretion of the metabolites of thromboxane (thromboxane B2) and prostacyclin (6-keto prostaglandin F1 alpha), and of endothelin and cyclic GMP as markers for changes in the balance of renal haemodynamic factors in the obese Zucker rat. 3. Obese fa/fa Zucker rats were hypertensive compared with their lean counterparts (161 +/- 3 and 138 +/- 3 mmHg respectively, P < 0.01); obese animals were also markedly proteinuric (16.7 +/- 6.7 versus 1.1 +/- 0.1 mg/ml) and albuminuric (8.3 +/- 2.9 versus 0.4 +/- 0.25 mg/ml) and excreted less creatinine than lean animals (all P < 0.01). Urinary excretion of endothelin was greater in obese rats (123 +/- 24 versus 62 +/- 10 pg/15 h, P < 0.05) as was the level of pre-proendothelin mRNA, but excretion of cyclic GMP was depressed (12.5 +/- 1.6 versus 27.2 +/- 3.1 nmol/ 15 h, P < 0.01). Histological examination of kidneys from obese animals showed evidence of focal glomerulosclerosis and cortical tubular damage. 4. These results show that increased urinary endothelin is associated with proteinuria and early stage nephropathy in this animal model of non-insulin-dependent diabetes mellitus. This finding, coupled with a decreased excretion of cyclic GMP, suggests that these increased renal vasoconstrictor/vasodilator forces might contribute to the renal functional changes in non-insulin-dependent diabetes mellitus.
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PMID:Elevated renal endothelin-I clearance and mRNA levels associated with albuminuria and nephropathy in non-insulin-dependent diabetes mellitus: studies in obese fa/fa Zucker rats. 949 94

Obese hypertensives have increased nonesterified fatty acids (NEFAs) and alpha-adrenergic vascular reactivity. Raising NEFAs locally with intralipid and heparin augments dorsal hand venoconstrictor responses to phenylephrine, an alpha(1)-adrenoceptor agonist. The enhanced venoconstrictor responses were reversed by indomethacin. The findings suggest that raising NEFAs leads to the generation of cyclooxygenase (COX) product(s) that enhance vascular reactivity. To test this notion, 6-keto-PGF(1alpha) and TxB(2), the stable metabolites of prostaglandin H(2) (PGH(2)); prostacyclin (PGI(2)); and thromboxane (TxA(2)), were measured approximately 1.5 to 2 cm downstream of a dorsal hand vein infusion of intralipid and heparin (n=10) or saline and heparin (n=5) for 2 hours each. During the third hour, intralipid and heparin (experimental) and saline and heparin (control) were continued, and either saline (control) or indomethacin (intervention) were infused. Intralipid and heparin raised local 6-keto PGF(1alpha) concentrations by 350% to 500% (P<0.005), but saline and heparin did not (P=NS). TxB(2) levels did not change significantly with any infusion. Infusion of indomethacin during the third hour of intralipid and heparin lowered plasma 6-keto-PGF(1alpha) (P<0.05), whereas infusion of saline with intralipid and heparin did not (P=NS). Oleic and linoleic acids at 100 micromol/L, increased 6-keto-PGF(1alpha) in vascular smooth muscle cells (VSMCs) through a protein kinase C and extracellular, signal-regulated kinase independent pathway. However, oleic and linoleic acids increased intracellular Ca(2+) in VSMCs. The data indicate that NEFAs induce the production of COX products, perhaps via Ca(2+)-dependent activation of phospholipase A(2). The COX product(s) may contribute to increased vascular alpha-adrenergic reactivity among insulin-resistant individuals when NEFAs are elevated.
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PMID:Lipids stimulate the production of 6-keto-prostaglandin f(1alpha) in human dorsal hand veins. 1164 Dec 99

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

The perimenopausal period is the time of important changes in endocrine function often accompanied by somatic and psychoemotional disturbances. The influence of menopause on dramatic increase of blood pressure especially in older women is not clearly established. It may be due to hypoestrogenism, obesity and hyperinsulinism present after menopause which cause endothelial dysfunction characterized by diminished synthesis of nitric oxide and prostacyclin and lack of restrain of synthesis of endothelin. As consequence there is prevalence of vasoconstrictive factors which promotes development of hypertension in this group of women. Arterial hypertension in perimenopausal women is becoming nowadays very important social problem for the sake of observed increasing percent of older patients and frequent cardiovascular complications accompanying this condition.
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PMID:[Arterial hypertension in perimenopausal women]. 1236 78

High fat intake is associated with fat mass gain through fatty acid activation of peroxisome proliferator-activated receptors delta and gamma, which promote adipogenesis. We show herein that, compared to a combination of specific agonists to both receptors or to saturated, monounsaturated, and omega-3 polyunsaturated fatty acids, arachidonic acid (C20:4, omega-6) promoted substantially the differentiation of clonal preadipocytes. This effect was blocked by cyclooxygenase inhibitors and mimicked by carbacyclin, suggesting a role for the prostacyclin receptor and activation of the cyclic AMP-dependent pathways that regulate the expression of the CCAAT enhancer binding proteins beta and delta implicated in adipogenesis. During the pregnancy-lactation period, mother mice were fed either a high-fat diet rich in linoleic acid, a precursor of arachidonic acid (LO diet), or the same isocaloric diet enriched in linoleic acid and alpha-linolenic acid (LO/LL diet). Body weight from weaning onwards, fat mass, epididymal fat pad weight, and adipocyte size at 8 weeks of age were higher with LO diet than with LO/LL diet. In contrast, prostacyclin receptor-deficient mice fed either diet were similar in this respect, indicating that the prostacyclin signaling contributes to adipose tissue development. These results raise the issue of the high content of linoleic acid of i) ingested lipids during pregnancy and lactation, and ii) formula milk and infant foods in relation to the epidemic of childhood obesity.
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PMID:Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern? 1257 9

The endothelium has several diverse functions in maintaining vascular integrity in terms of structure and function. Two key vasodilators, nitric oxide (NO) and prostacyclin, maintain the vascular pathway, inhibit platelet aggregation, and are antithrombotic. More recently, they have been shown to be anti-inflammatory, and thus are potentially antiatherogenic. It has recently been noted that insulin stimulates NO release by the endothelium. Insulin is a vasodilator, has antiplatelet activity, and is anti-inflammatory. Similar anti-inflammatory effects of thiazolidinediones (TZDs), troglitazone and rosiglitazone, suggest that they too may have potential antiatherogenic effects. These effects of insulin and TZDs are important because the two major states of insulin resistance, obesity and type 2 diabetes, are associated with a marked increase in atherosclerosis coronary heart disease, and stroke. These recent observations have extremely momentous implications for the understanding of the pathogenesis of atherosclerosis in insulin-resistant states and for a rational approach to their comprehensive treatment, including the prevention of atherosclerosis and its complications.
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PMID:Endothelium, inflammation, and diabetes. 1264 90

Insulin resistance syndrome (also called syndrome X) includes obesity, diabetes, hypertension, and dyslipidemia and is a complex phenotype of metabolic abnormalities. The disorder poses a major public health problem by predisposing individuals to coronary heart disease and stroke, the leading causes of mortality in Western countries. Given that hypertension, diabetes, dyslipidemia, and obesity exhibit a substantial heritable component, it is postulated that certain genes may predispose some individuals to this cluster of cardiovascular risk factors. Emerging data suggest that peroxisome proliferator-activated receptors (PPARs), including alpha, gamma, and delta, are important determinants that may provide a functional link between obesity, hypertension, and diabetes. It has been well documented that hypolipidemic fibrates and antidiabetic thiazolidinediones are synthetic ligands for PPAR alpha and PPAR gamma, respectively. In addition, PPAR natural ligands, such as leukotriene B4 for PPAR alpha, 15-deoxy-delta 12,14-prostaglandin J2 for PPAR gamma, and prostacyclin for PPAR delta, are known to be eicosanoids and fatty acids. Studies have documented that PPARs are present in all critical vascular cells: endothelial cells, vascular smooth muscle cells, and monocyte-macrophages. These observations suggest that PPARs not only control lipid metabolism but also regulate vascular diseases such as atherosclerosis and hypertension. In this review, we present structure and tissue distribution of PPAR nuclear receptors, discuss the mechanisms of action and regulation, and summarize the rapid progress made in this area of study and its impact on the cardiovascular system.
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PMID:Peroxisome proliferator-activated receptors and the cardiovascular system. 1285 55

Endothelial dysfunction is a critical factor in the development of vascular disease in patients with diabetes mellitus. Maintenance of the vascular tone and luminal diameter of a blood vessel is dependent on the net balance of vasoconstrictor and vasodilator forces. In both diabetes and obesity, vascular reactivity is abnormal. After ischemia, carbon dioxide challenge, thermal challenge, or exercise, individuals with diabetes do not exhibit the increase in blood flow or vasodilation observed in persons without diabetes. The mechanisms involved in abnormal reactivity may include both the endothelium and vascular smooth muscle. Major vasodilator factors that act on vascular smooth muscle cells are nitric oxide, prostacyclin, and hyperpolarizing factor. The main vasoconstrictors are endothelin, angiotensin II, norepinephrine, serotonin, and thromboxane A(2). In patients with diabetes, there is an increase in vasoconstrictors and a decrease in vasodilators. Thiazolidinediones (TZDs) improve vasodilative responses, which may be of importance in the treatment of vascular disease. The TZDs have anti-inflammatory effects and suppress free fatty acids and reactive oxygen species at the endothelial level, which may contribute to the improved vascular reactivity observed in patients treated with these agents. In addition, these effects of TZDs may have implications for reducing the incidence and severity of atherosclerosis in the long term.
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PMID:Vascular reactivity and thiazolidinediones. 1467 71

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