Angiotensin II receptor blockade and skeletal muscle metabolism in overweight and obese adults with elevated blood pressure (original) (raw)
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The Journal of Clinical Endocrinology & Metabolism, 2004
The present study was designed to investigate the effects of angiotensin II (Ang II) on adipose and skeletal muscle tissue blood flow and lipolysis in normal-weight and obese subjects using the microdialysis technique. Microdialysis probes were placed in the abdominal sc adipose tissue left and right from the umbilicus and in the gastrocnemius muscle of both legs in eight normal-weight and eight obese men. Probes were consecutively perfused with 1.0 nM Ang II, 1.0 M Ang II, and 1.0 M Ang II ؉ 48 M hydralazine or with Ringer solution (control). Ethanol and glycerol concentrations in the dialysate were measured as an indicator of local blood flow and lipolysis, respectively. Ang II caused an increase in ethanol outflow/inflow ratio, compared with baseline values both in adipose tissue (average of both groups, Ang 1.0 nM: 0.03 ؎ 0.01, P ؍ 0.02; Ang 1.0 M: 0.05 ؎ 0.01, P < 0.01) and muscle (average of both groups, Ang 1.0 nM: 0.02 ؎ 0.01, P ؍ 0.09; Ang 1.0 M: 0.04 ؎ 0.01, P ؍ 0.01), indicating a decrease in local blood flow. These effects were not significantly different in obese and normal-weight subjects. The decrease in local blood flow was accompanied by unchanged interstitial glycerol concentrations in adipose tissue (except during the supraphysiological dose) and skeletal muscle, suggesting that Ang II inhibits lipolysis in both tissues. Thus, the present data suggest that Ang II decreases local blood flow in a dose-dependent manner and inhibits lipolysis both in adipose and skeletal muscle tissue. These effects were not significantly different in obese and normal-weight subjects in both tissues. (J Clin Endocrinol Metab 89: 2690 -2696, 2004)
Vascular Response to Angiotensin II in Upper Body Obesity
Hypertension, 2004
Upper body obesity is associated with insulin resistance, hypertension, and endothelial dysfunction. We examined forearm vascular function in response to vasodilator (endothelium-dependent and endothelium-independent) and vasoconstrictor stimuli in 8 normotensive, upper body/viscerally obese men with a positive family history of hypertension and 8 age-matched nonobese men. We also measured body composition and insulin regulation of free fatty acid (FFA) and glucose metabolism. Forearm blood flow was measured before and during brachial artery infusions of acetylcholine (Ach), sodium nitroprusside (NTP), and angiotensin II (±nitric oxide synthase [NO]) synthase blockade with N G -monomethyl l -arginine [ l -NMMA]). On a separate day, baseline and insulin-regulated glucose ([3- 3 H]glucose) and FFA ([9,10- 3 H]palmitate) turnover were measured. The vasoconstrictor response to angiotensin II was greater ( P <0.05) in obese men than in nonobese men, whereas endothelium-dependent vasod...
Diabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular Disease, 2006
E ndothelial dysfunction is a pivotal early event in the development of atherosclerosis and a characteristic feature of obesity. This study was designed to investigate the effect of angiotensin-converting enzyme (ACE) inhibition on endothelial function in people who were obese but otherwise healthy. We performed a doubleblind, randomised, placebo-controlled study examining the effect of the ACE inhibitor perindopril (4 mg per day) on flow-mediated vasodilatation (FMD) of the brachial artery, arterial blood pressure, glucose homeostasis and inflammatory cytokines. Eighteen obese subjects (all body mass index > 30 kg/m 2 ) were randomised to receive perindopril or placebo for four weeks. Perindopril led to a fall in systolic blood pressure from 131 (standard error of mean [SEM] 3) to 117(5) mmHg and diastolic blood pressure from 74(4) mmHg to 68(4) mmHg, both p<0.001. Despite this fall in blood pressure, ACE inhibition had no effect on FMD, 8.2 (1.2)% versus 8.3 (1.5)%, p=0.9. ACE inhibition had no effect on insulin, lipids or circulating cytokines. In healthy obese humans, despite a significant reduction in blood pressure, ACE inhibition had no effect on FMD.
Angiotensin II: a hormone that affects lipid metabolism in adipose tissue
Background: Alterations in adipose tissue lipolysis may contribute to the pathophysiology of obesity and insulin resistance. We examined the effects of angiotensin II (Ang II) on abdominal subcutaneous adipose tissue lipolysis in humans. Methods and results: First, adipocytes obtained from nine normal weight and seven obese subjects were stimulated with Ang II (10 À14 -10 À6 M). Glycerol concentration in the medium, used as an indicator of adipocyte lipolysis, was significantly reduced (B20%) after Ang II stimulation in adipocytes from normal weight (P ¼ 0.04) and obese subjects (Po0.001). Based on these observations, adipocytes of seven additional obese subjects were stimulated with lower doses of Ang II (10 À17 -10 À6 M) in the presence and absence of Ang II type 1 (AT 1 ) receptor blockade. Lipolysis was dose dependently inhibited by B20 to 25% after Ang II stimulation (P ¼ 0.001). AT 1 receptor blockade completely abolished the Ang II-induced effects (P ¼ 0.35). Conclusion: Ang II directly inhibits abdominal subcutaneous adipocyte lipolysis in normal weight and obese subjects via the AT 1 receptor.
Metabolic and Hemodynamic Response of Adipose Tissue to Angiotensin II
Obesity, 2001
BOSCHMANN, MICHAEL, JENS RINGEL, SUSANNE KLAUS, AND ARYA M. SHARMA. Metabolic and hemodynamic response of adipose tissue to angiotensin II. Obes Res. 2001;9:486-491. Objective: Recent studies have revealed the presence of a local renin-angiotensin system in adipose tissue. To examine the possible role of this system in adipose tissue, we performed microdialysis studies on the effect of angiotensin II (Ang II) on blood flow and metabolism in abdominal subcutaneous adipose tissue (aSAT) and femoral subcutaneous adipose tissue (fSAT) in young healthy men. Research Methods and Procedures: Using the microdialysis technique, two different protocols were run perfusion with Ringer's solution ϩ 50 mM ethanol with the subsequent addition of 125, 250, and 500 g/liter Ang II (n ϭ 8) and Ringers's solution ϩ 50 mM ethanol with the subsequent addition of isoproterenol (1 M) alone and in combination with 500 g/liter Ang II (n ϭ 6). Dialysate concentrations of ethanol, glycerol, glucose, and lactate were measured for estimating blood flow (ethanol dilution technique), lipolysis, and glycolysis, respectively. Results: Perfusion with Ang II resulted in a dose-dependent decrease in blood flow (fSAT Ͼ aSAT), lipolysis (fSAT Ͼ aSAT), and glucose uptake (fSAT ϭ aSAT). Isoproterenol increased blood flow and lipolysis at both sites and those effects could be returned to baseline values by the addition of Ang II in aSAT but not fSAT. Discussion: In conclusion, our data indicate that in addition to its well-known vasoconstricting effect, Ang II inhibits lipolysis in adipose tissue, whereby femoral fat depots seem to be more sensitive to this effect than abdominal depots.
Favorable Vascular Actions of Angiotensin-(1–7) in Human Obesity
Hypertension, 2018
Obese patients have vascular dysfunction related to impaired insulin-stimulated vasodilation and increased endothelin-1–mediated vasoconstriction. In contrast to the harmful vascular actions of angiotensin (Ang) II, the angiotensin-converting enzyme 2 product Ang-(1–7) has shown to exert cardiovascular and metabolic benefits in experimental models through stimulation of the Mas receptor. We, therefore, examined the effects of exogenous Ang-(1–7) on vasodilator tone and endothelin-1–dependent vasoconstriction in obese patients. Intra-arterial infusion of Ang-(1–7) (10 nmol/min) resulted in significant increase in unstimulated forearm flow ( P =0.03), an effect that was not affected by the Mas receptor antagonist A779 (10 nmol/min; P >0.05). In the absence of hyperinsulinemia, however, forearm flow responses to graded doses of acetylcholine and sodium nitroprusside were not different during Ang-(1–7) administration compared with saline (both P >0.05). During infusion of regular ...
Oxidative Medicine and Cellular Longevity
Angiotensin 1-7 (Ang 1-7) enhances insulin signaling and glucose transport activity in the skeletal muscle. The aim of our study was to evaluate the effect of AVE0991, a nonpeptide Mas receptor agonist, on the metabolic parameters, expression of RAS components and markers of oxidative stress, and insulin signaling in the skeletal morbidly obese rats. 33-week-old male obese Zucker rats were treated with vehicle and AVE0991 (0.5 mg/kg BW/day) via osmotic minipumps for two weeks. Gene expressions were determined by qPCR and/or Western blot analysis in musculus quadriceps. The enzymatic activities were detected flourometrically (aminopeptidase A) or by colorimetric assay kit (protein tyrosine phosphatase 1B). Administration of AVE0991 enhanced insulin signaling cascade in the skeletal muscle, reflected by improved whole-body glucose tolerance. It has been shown that reactive oxygen species (ROS) have insulin-mimetic action in muscle. The expression of renin receptor, transcription facto...
2006
To clarify the mechanism of the effects of angiotensin II AT 1 receptor antagonists on adipose tissue, we treated 8 week-old male Wistar Kyoto rats with the angiotensin II AT 1 receptor antagonist Candesartan cilexetil (10 mg/kg/day) for 18 weeks. Candesartan cilexetil reduced body weight gain, decreased fat tissue mass due to hypotrophy of epididymal and retroperitoneal adipose tissue and decreased adipocyte size without changing the number of adipocytes. Candesartan cilexetil decreased serum leptin levels and epididymal leptin mRNA, increased serum adiponectin levels and epididymal adiponectin mRNA, decreased epididymal tumor necrosis factor alpha (TNFα) mRNA, and increased fatty acid synthase mRNA. Considered free of peroxisome proliferator-activated receptor γ (PPARγ) agonist activity, Candesartan cilexetil increased epididymal expression of PPARγ mRNA. The effects of Candesartan cilexetil on adipokine production and release may be attributable to PPARγ activation and/or decrease in adipocyte cell size. In addition, Candesartan cilexetil treatment increased the expression of epididymal angiotensin II AT 2 receptor mRNA and protein and decreased the expression of renin receptor mRNA. These results suggest that Candesartan cilexetil influences lipid metabolism in adipose tissue by promoting adipose tissue rearrangement and modulating adipokine expression and release. These effects are probably consequences of local angiotensin II AT 1 receptor inhibition, angiotensin II AT 2 receptor stimulation, and perhaps additional angiotensin II-independent mechanisms. Our results indicate that the activity of local renin-angiotensin system plays an important role in adipose tissue metabolism. The decrease in the pro-inflammatory cytokine TNFα and the increase in the anti-inflammatory adipokine adiponectin indicate that Candesartan cilexetil may exert significant anti-inflammatory properties.
SHORT COMMUNICATION Angiotensin II: a hormone that affects lipid metabolism in adipose tissue
2000
Background: Alterations in adipose tissue lipolysis may contribute to the pathophysiology of obesity and insulin resistance. We examined the effects of angiotensin II (Ang II) on abdominal subcutaneous adipose tissue lipolysis in humans. Methods and results: First, adipocytes obtained from nine normal weight and seven obese subjects were stimulated with Ang II (10� 14-10� 6 M). Glycerol concentration in the
Therapeutic advances in cardiovascular disease, 2013
We tested the hypothesis that olmesartan, an angiotensin II receptor blocker (ARB) devoid of peroxisome proliferator-activated receptor γ agonist activity, would improve whole-body insulin sensitivity in overweight and obese individuals with elevated blood pressure (BP). Sixteen individuals (8 women, 8 men; age=49.5 ± 2.9 years; body mass index=33.0 ± 1.7 kg/m2) were randomly assigned in a crossover manner to control and ARB interventions. Insulin sensitivity was determined from intravenous glucose tolerances tests before and after each 8-week intervention. BP, body weight, body fat, lipid and lipoprotein concentrations, and insulin sensitivity were similar at baseline for both treatments (all p > 0.05). Diastolic BP and triglyceride concentrations were higher (p = 0.007 and 0.042 respectively) at baseline for the ARB compared with the control intervention. Systolic (-11.7 mmHg; p = 0.008) and diastolic (-12.1 mmHg; p = 0.0001) BP decreased, however insulin sensitivity did not ch...