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

To determine the impact of the renin-angiotensin-aldosterone system on left ventricular function and structure, 36 untreated patients with essential hypertension (WHO class I and II) were examined. Posterior wall thickness, relative wall thickness, and left ventricular mass were determined by M-mode echocardiography. Plasma renin activity, aldosterone, angiotensin I, and angiotensin II levels were measured by radioimmunoassay. Plasma renin activity was related to 24-hour urinary sodium excretion. Of all the endocrine parameters, only the angiotensin II level correlated with posterior wall thickness (r = 0.50, p less than 0.05) and relative wall thickness (r = 0.46, p less than 0.05). This relationship was confirmed by stepwise multiple regression analysis taking arterial pressure, obesity, and sodium excretion into account (p less than 0.05). Plasma renin activity but not the angiotensin II level correlated positively with the ejection fraction (r = 0.42, p less than 0.05) and velocity of circumferential fiber shortening (r = 0.57, p less than 0.01). Thus, angiotensin II emerged as a determinant of left ventricular structural adaptation in essential hypertension.
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PMID:Does the renin-angiotensin-aldosterone system modify cardiac structure and function in essential hypertension? 297 63

Hepatic plasma membranes of female obese mice C57 BL-6 orl ob/ob (ob/ob mice) completely lack vasopressin (VP) receptors of the V1 type whereas kidney VP receptors are normally expressed and functionally coupled to adenylate cyclase. To discover if these alterations are linked to a genetic defect of the V1 receptor, we have studied the binding of VP on liver and kidney membranes of two other models, female diabetic mice C57 BL-6 orl db/db (db/db mice) and female Zucker rats Fatty/orl fa/fa (fa/fa rats), which exhibit different temporal pattern of obesity, hyperinsulinemia and insulin resistance. In addition, since VP is known to exert its vascular response through stimulation of V1 receptors, we have studied the reactivity of VP of isolated tail artery in the three different models, ob/ob and db/db mice and fa/fa rats, and in their respective controls. In all cases, VP kidney receptors and VP vascular reactivity are normal. db/db mice exhibit a marked decrease in hepatic VP receptors whereas a 50% decrease was observed in 32 week fa/fa rats. Angiotensin II and prazosin binding sites are still present as well as the adenylate cyclase response to glucagon. These results suggest that the specific alteration in liver VP receptors is not related to a defect in V1 receptor genetic expression but is specific for liver and appears to parallel the level of hyperinsulinemia and/or insulin resistance.
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PMID:Reduction in hepatic but not in renal and vascular vasopressin receptor number in hyperinsulinemic mice and rats. 609 84

Obesity is considered to be a major factor in the pathogenesis of hypertension in industrialized countries. Recent studies have suggested that the kidneys may play an important role in the development of obesity-induced hypertension. The purpose of this study was to determine whether obesity-induced hypertension is associated with abnormalities in the pressure-natriuresis relation. Renal function studies were performed in anesthetized control dogs (body weight, 20.2 +/- 0.8 kg) and obese dogs (body weight, 26.4 +/- 0.7 kg) that were maintained on a high-fat diet for 5 to 6 weeks. Mean arterial pressure averaged 122 +/- 5 mm Hg in the control group (n = 6) and 148 +/- 7 mm Hg in the obese group (n = 8). The effects of renal perfusion pressure on renal hemodynamics as well as sodium and water excretions were examined at five levels of renal perfusion pressure ranging from 75 to 165 mm Hg. Pressure-natriuretic and diuretic responses were reduced in the obese dogs by 40% to 50%. The renal blood flow and glomerular filtration rate autoregulatory responses and fractional lithium excretion responses to changes in renal perfusion pressure were similar in the control and obese dog groups. Associated with the attenuated natriuretic response to renal perfusion pressure in the obese dogs were significant elevations in plasma renin activity (4.3 +/- 1.6 versus 1.6 +/- 0.5 ng angiotensin I/mL per hour), plasma aldosterone concentration (34.4 +/- 6.4 versus 15.3 +/- 3.2 ng/dL), and plasma insulin concentration (30.5 +/- 6.8 versus 20.9 +/- 2.9 IU/mL).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormal pressure natriuresis in the dog model of obesity-induced hypertension. 828 80

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

We designed our studies to determine whether blood pressure is elevated in obese Zucker rats compared with lean control rats and to test the importance of the renin-angiotensin and adrenergic nervous systems in long-term blood pressure control in this genetic model of obesity. We monitored mean arterial pressure 24 hours per day using computerized methods in 13- to 14-week-old lean and obese Zucker rats maintained on a fixed, normal sodium intake (3.3 mmol/d). Mean arterial pressure (average of 5 days) was higher in obese (100 +/- 1 mm Hg) than in lean (86 +/- 1) rats. Although control plasma renin activity was lower in obese than in lean rats (3.66 +/- 0.15 versus 5.48 +/- 0.11 ng angiotensin I/mL per hour), blood pressure sensitivity to exogenous angiotensin II was greater in obese than in lean rats. Blockade of endogenous angiotensin II receptors with losartan (10 mg/kg per day) for 7 days also caused a greater decrease in blood pressure in obese (36 +/- 2 mm Hg, n = 6) than in lean (25 +/- 1, n = 5) rats. However, combined alpha- and beta-adrenergic blockade with terazosin (10 mg/kg per day) and propranolol (10 mg/kg per day), respectively, for 8 days caused only modest decreases in blood pressure in obese (9 +/- 3 mm Hg, n = 8) and lean (4 +/- 2, n = 6) rats, despite effective alpha- and beta-adrenergic blockade. These results suggest that increased arterial pressure in obese Zucker rats depends in part on angiotensin II. However, additional mechanisms may also contribute to increased blood pressure in obese Zucker rats.
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PMID:Hypertension in obese Zucker rats. Role of angiotensin II and adrenergic activity. 895 95

Angiotensin II regulates blood pressure and may affect adipogenesis and adipocyte metabolism. Angiotensin II is produced by cleavage of angiotensinogen by renin and angiotensin-converting enzyme in the circulation. In addition, angiotensin II may be produced in various tissues by enzymes of the renin-angiotensin system (RAS) or the nonrenin-angiotensin system (NRAS). We have analyzed the expression of angiotensinogen and enzymes required for its conversion to angiotensin II in human adipose tissue. Northern blot demonstrated angiotensinogen expression in adipose tissue from nine obese subjects. Western blot revealed a distinct band of expected size of the angiotensinogen protein (61 kDa) in isolated adipocytes. RT-PCR, followed by Southern blot, demonstrated renin expression in human adipose tissue. Angiotensin-converting enzyme messenger RNA was detected by RT-PCR, and the identity of the PCR products was verified by restriction enzyme cleavage. Transcripts for cathepsin D and cathepsin G, components of the NRAS, were detected by RT-PCR, verified by restriction enzyme cleavage. We conclude that human adipose tissue expresses angiotensinogen and enzymes of RAS and NRAS. This opens the possibility that angiotensinogen-derived peptides, produced in adipose tissue itself, may affect adipogenesis and play a role in the pathogenesis of obesity.
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PMID:Human adipose tissue expresses angiotensinogen and enzymes required for its conversion to angiotensin II. 981 70

Essential hypertension is a complex disease influenced by different genetic and environmental factors. The renin-angiotensin system (RAS) is implicated in blood pressure regulation. Angiotensinogen (AGT) is the precursor of the biologically active angiotensin II (Ang II). Initial studies on hypertensive siblings and case-control studies indicated the important role of the angiotensinogen gene (AGT) for the predisposition to essential hypertension, preeclampsia and obesity-related hypertension. Recently, different AGT polymorphisms had been identified and analyzed in case-control studies. The aim of present studies is the analysis of potentially functional AGT variants (C-532T, G-6A), which might be responsible for the regulation of gene expression and therefore AGT generation. The A-6 allele is in complete linkage disequilibrium with the T235 allele and is associated with higher AGT expression in vitro. Segregation linkage analysis demonstrated that the C-532T polymorphism influences plasma AGT variability more significantly than the G-6A variant. Since the C-532T polymorphism is located within a AP-2 consensus element, functional promoter analyses are required. The understanding of the molecular basis of RAS in essential hypertension may provide us with new and more specific pharmacological agents and perhaps the ability to individualize antihypertensive treatment.
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PMID:[Role of the angiotensinogen gene for essential hypertension]. 1071 6

Obese hypertensive patients with cardiovascular risk factor clustering and increased risk for atherosclerotic disease have increased plasma nonesterified fatty acid levels, including oleic acid (OA), and a more active renin-angiotensin-aldosterone system. Vascular smooth muscle cell (VSMC) migration and proliferation participate in the development of atherosclerotic plaque. OA and angiotensin (Ang) II induce synergistic mitogenic responses in VSMCs through sequential signaling pathways dependent on the activation of protein kinase C (PKC), oxidants (reactive oxygen species, ROS), and extracellular signal-regulated kinase (ERK) activation. We tested the hypotheses that (1) OA and Ang II have additive or synergistic effects on VSMC migration and (2) PKC, ROS, and mitogen-activated protein kinase are critical signaling molecules. OA at 100 micromol/L increases VSMC migration 60+/-10% over control (P:<0.001). Ang II (10(-)(9) mol/L) increases VSMC migration by 62+/-13% and 73% over control, respectively (P:<0.01). Coincubation of cells with OA and Ang II produces a nearly additive increase in VSMC cell migration at 107+/-20% (P:<0.01). Increases in VSMC migration induced by OA alone and combined with Ang II were reduced by PKC inhibition and downregulation. VSMC migration in response to OA alone and with Ang II was also inhibited by N:-acetyl-cysteine, MEK inhibition, and ERK antisense. VSMC migration in response to OA alone or combined with Ang II is dependent on activation of PKC, ROS, and ERK activation, further raising the possibility that increased plasma nonesterified fatty acids and an activated renin-angiotensin-aldosterone system in subjects with the risk factor cluster contribute to accelerated atherosclerosis through a PKC, ROS, and ERK-dependent signaling pathway.
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PMID:Signaling events mediating the additive effects of oleic acid and angiotensin II on vascular smooth muscle cell migration. 1123 Feb 90

Plasminogen activator inhibitor (PAI)-1 is the main inhibitor of the fibrinolytic system and was recently shown to be produced by adipose cells. Obesity is associated with an increased production and release of PAI-1 protein. The aim of this study was to investigate the role of angiotensin (Ang) II and its degradation products for PAI-1 release from human adipose cells. For this purpose, we used the model of in vitro differentiated human adipocytes in primary culture. Exposure of human adipocytes to Ang II resulted in a dose- and time-dependent stimulation of PAI-1 release into the culture medium. The maximum effect of Ang II was found at a concentration of 10(-5) mol/L for 48 hours, increasing PAI-1 release by 276+/-53% compared with control cultures (P<0.05). This stimulation was preceded by an increase in specific PAI-1 mRNA copies by 65+/-12% (P<0.05), with a maximum after 6 hours. Incubation of adipocytes with 10(-5) mol/L Ang III and Ang IV, respectively, also resulted in a stimulation of PAI-1 release into the medium by 195+/-60% (P<0.05) and 142+/-24% (P<0.05), respectively, compared with control cultures. Addition of the angiotensin-receptor subtype 1 (AT(1)) blocker candesartan abolished the stimulatory action of Ang II and its metabolites, indicating that this effect is mediated by AT(1). Addition of the AT(1) blocker alone to unstimulated cultures reduced PAI-1 release by 41%+/-25% (P<0.05), suggesting that endogenous Ang II synthesis contributes to PAI-1 secretion from adipose tissue in an autocrine/paracrine manner. In conclusion, Ang II and its metabolites promote PAI-1 production and release by human fat cells and may contribute to the impairment of the fibrinolytic system typical for obesity. AT(1) receptor blockade reduces basal and abolishes Ang II-stimulated PAI-1 release from human adipocytes.
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PMID:Angiotensin II and its metabolites stimulate PAI-1 protein release from human adipocytes in primary culture. 1135 50

Angiotensin (Ang) II is the active component of the renin-angiotensin-system (RAS), but its degradation products have also been shown to exhibit biological activity. This system, which mainly controls blood pressure and electrolyte homeostasis, was recently found to be completely expressed in human adipose tissue. The major determinant in the fibrinolytic system is the plasminogen activator inhibitor-1 (PAI-1). Both PAI-1 and components of the RAS are over-expressed in the obese state. We have recently shown that Ang II is able to induce PAI-1 expression and release via the AT1-receptor in human fat cells in primary culture, and have provided the first evidence that two metabolites, Ang III and Ang IV, may have a similar stimulatory effect on PAI-1 release. We have now performed additional experiments to further characterize the role of the angiotensin peptides in the production of PAI-1. Ang III and Ang IV showed a time- and dose-dependent stimulation of PAI-1 protein release. Concomitantly, mRNA-levels were markedly elevated. Using specific receptor blockers, all angiotensin peptides seem to induce PAI-1 expression via the angiotensin receptor subtype 1. However, components of the renin-angiotensin-system seem to play an important role in the control of fibrinolysis in adipose tissue. We conclude that PAI-1 production by adipose tissue may contribute to the elevated thromboembolic risk in obesity.
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PMID:Effect of angiotensin peptides on PAI-1 expression and production in human adipocytes. 1138 21


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