endothelin-1 and Hypertriglyceridemia

Previous studies of the health effects of low-fat milk or dairy consumption on the metabolic syndrome have yielded inconsistent results. The present study aimed to investigate the effects of low-fat milk consumption on traits associated with the metabolic syndrome, as well as inflammatory and atherogenic biomarkers, in Korean adults with the metabolic syndrome.. Overweight Koreans with the metabolic syndrome (n = 58) were recruited and randomly assigned to either the low-fat milk or control group. The low-fat milk group was instructed to consume two packs of low-fat milk per day (200 mL twice daily) for 6 weeks, and the control group was instructed to maintain their habitual diet. Clinical investigations were conducted during the screening visit, on study day 0, and after 6 weeks.. No significant differences in changes in body mass index, blood pressure, lipid profile and adiponectin levels, as well as levels of inflammatory markers, oxidative stress markers and atherogenic markers, were found between the low-fat milk and control groups. However, compared to the controls, significant favourable decreases in serum soluble vascular adhesion molecule-1 and endothelin-1 levels were found in the 12 subjects with high blood pressure and in the 18 subjects with hypertriglyceridaemia in the low-fat milk group.. The present study did not demonstrate an overall beneficial effect of low-fat milk consumption in subjects with the metabolic syndrome. However, low-fat milk consumption may have a favourable effect on atherogenic markers in subjects with high blood pressure or hypertriglyceridaemia.

Topics: Adult; Animals; Atherosclerosis; Biomarkers; Body Mass Index; Diet, Fat-Restricted; Endothelin-1; Follow-Up Studies; Humans; Hypertension; Hypertriglyceridemia; Inflammation Mediators; Insulin Resistance; Metabolic Syndrome; Middle Aged; Milk; Overweight; Oxidative Stress; Patient Dropouts; Republic of Korea; Risk Factors; Vascular Cell Adhesion Molecule-1

Atherosclerosis is a postprandial phenomenon. The balanced n-6/n-3 PUFA ratio contributing to the prevention of atherosclerosis has been well shown, but the effect of the ratio on postprandial metabolism has not been fully investigated. The aim of this study was to investigate the effects of the n-6/n-3 PUFAs ratio on postprandial metabolism in hypertriacylglycerolemia patients, comparing them to healthy controls.. Test meals with 0.97 (high n-3) and 8.80 (low n-3) n-6/n-3 PUFAs ratio were administered in a randomized crossover design to 8 healthy and 8 hypertriacylglycerolemia subjects. Blood samples were collected for 8 hours after meals to measure triglyceride (TG), total cholesterol (TC), HDL, ApoA, ApoB, glucose, insulin, inflammatory makers including tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), endothelial function including nitric oxide (NO) and endothelin-1 (ET-1).. According to repeated-measures ANOVA, the postprandial response of lipid, glucose, insulin, inflammation and endothelial function were not significantly different between meals. The postprandial TG and NO response were significantly different between healthy control (HC) and hypertriglyceridemia group (HTG) after both meals (P < 0.01). After both meals maximal change and iAUC for TG was all higher in HTG group than HC group, the difference was significant after low n-3 meal but not after high n-3 meal. The concentration of glucose, insulin, IL-6, TNFα and ET-1 at each time point was higher and NO was lower in HTG group, but the maximal change and iAUC had no significant difference except for iAUC of insulin, IL-6 and diAUC of NO after low n-3 meal.. The ratio of n-6 and n-3 maybe do not acutely influence the postprandial metabolism, inflammatory response and endothelial function, but the low n-3 meal can strengthen the difference between HTG and HC group.

Topics: Adult; Apolipoproteins A; Apolipoproteins B; Area Under Curve; Blood Glucose; Cholesterol, HDL; Cross-Over Studies; Endothelin-1; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Humans; Hypertriglyceridemia; Insulin; Interleukin-6; Lipid Metabolism; Male; Middle Aged; Nitric Oxide; Postprandial Period; Triglycerides; Tumor Necrosis Factor-alpha

Cumulative evidence suggests that moderate red wine consumption protects the cardiovascular system. The effect of cultured cells derived from red grape berry (RGC) on blood pressure (BP) has not been investigated. We therefore studied the antihypertensive effects of oral consumption of RGC in experimental rat model of metabolic-like syndrome and assessed its effect on human umbilical vein endothelial cells (HUVECs).. Forty male Sprague-Dawley rats were fed for 5 weeks with either a high fructose diet (HFD) (n = 10) or HFD supplemented, during the last 2 weeks, with different doses (200, 400 and 800 mg/kg/day) of RGC suspended in their food (n = 30). BP, plasma triglycerides, insulin and adiponectin levels were measured at the beginning and after 3 and 5 weeks of diet. RGC effect on vasodilatation was evaluated by its ability to affect endothelin-1 (ET-1) production and endothelial nitric oxide synthase (eNOS) expression in HUVECs.. BP, plasma triglycerides, insulin and adiponectin increased significantly in rats fed with a HFD. The increase in BP, plasma triglycerides and insulin was attenuated by RGC supplementation. Incubation of HUVECs with RGC demonstrated a concentration-dependent inhibition of ET-1 secretion and increase in the level of eNOS, signaling a positive effect of RGC on vasodilatation.. In rats with metabolic-like syndrome, RGC decreased BP and improved metabolic parameters. These beneficial effects may be mediated by the cell constituents, highly rich with polyphenols and resveratrol, reside in their natural state.

Topics: Animals; Antihypertensive Agents; Cells, Cultured; Dietary Supplements; Endothelin-1; Fruit; Human Umbilical Vein Endothelial Cells; Humans; Hyperinsulinism; Hypertension; Hypertriglyceridemia; Hypolipidemic Agents; Male; Metabolic Syndrome; Nitric Oxide Synthase Type III; Pigments, Biological; Plant Extracts; Rats, Sprague-Dawley; Vasodilator Agents; Vitis

Functional and structural heterogeneity exists among skeletal muscle vascular beds related, in part, to muscle fiber type composition. This study was designed to delineate whether the vulnerability to vascular dysfunction in insulin resistance is uniformly distributed among skeletal muscle vasculatures and whether physical activity modifies this vulnerability. Obese, hyperphagic Otsuka Long-Evans Tokushima fatty rats (20 wk old) were sedentary (OSED) or physically active (OPA; access to running wheels) and compared with age-matched sedentary Long-Evans Tokushima Otsuka (LSED) rats. Vascular responses were determined in isolated, pressurized feed arteries from fast-twitch gastrocnemius (GFAs) and slow-twitch soleus (SFAs) muscles. OSED animals were obese, insulin resistant, and hypertriglyceridemic, traits absent in LSED and OPA rats. GFAs from OSED animals exhibited depressed dilation to ACh, but not sodium nitroprusside, and enhanced vasoconstriction to endothelin-1 (ET-1), but not phenylephrine, compared with those in LSED. Immunoblot analysis suggests reduced endothelial nitric oxide synthase phosphorylation at Ser1177 and endothelin subtype A receptor expression in OSED GFAs. Physical activity prevented reduced nitric oxide-dependent dilation to ACh, but not enhanced ET-1 vasoconstriction, in GFA from OPA animals. Conversely, vasoreactivity of SFAs to ACh and ET-1 were principally similar in all groups, whereas dilation to sodium nitroprusside was enhanced in OSED and OPA rats. These data demonstrate, for the first time, that SFAs from insulin-resistant rats exhibit reduced vulnerability to dysfunction versus GFAs and that physical activity largely prevents GFA dysfunction. We conclude that these results demonstrate that vascular dysfunction associated with insulin resistance is heterogeneously distributed across skeletal muscle vasculatures related, in part, to muscle fiber type and activity level.

Topics: Acetylcholine; Animals; Arteries; Endothelin-1; Hypertriglyceridemia; Insulin Resistance; Male; Muscle Fibers, Skeletal; Muscle, Skeletal; Nitroprusside; Obesity; Physical Conditioning, Animal; Rats; Rats, Inbred OLETF; Sedentary Behavior; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

Topics: Adult; Biomarkers; C-Reactive Protein; Cell Adhesion Molecules; Coronary Disease; Endothelin-1; Endothelium, Vascular; Humans; Hypertriglyceridemia; Inflammation; Interleukin-6; Male; Risk Factors; von Willebrand Factor

Insulin-elicited endothelin release in hypertriglyceridemic, hypertensive, hyperinsulinemic (HTG) rats was shown. Weanling male Wistar rats were given 30% sucrose in their drinking water for 20-24 wk. In vitro contractions of aorta and femoral arteries were elicited with 40 mM KCl. Endothelin release induced with KCl plus 50 microU/ml insulin resulted in increases in contractile responses: 41 +/- 5.9 and 57 +/- 6% for control and 65.5 +/- 6 and 95 +/- 9% for HTG aortas and femoral arteries, respectively. The endothelin ET(B)-receptor blocker BQ-788 decreased responses to KCl + insulin by 39 +/- 8 and 53 +/- 5% in control and 48 +/- 13 and 79 +/- 3.5% in HTG aortas and femoral arteries, respectively. The ET(A)-receptor antagonist PD-151242 inhibited these responses by 12 +/- 10 and 1 +/- 9% in control and by 51.5 +/- 9 and 58.5 +/- 1% in HTG aortas and femoral arteries, respectively. These results suggest that endothelin may contribute to the hypertension in this model.

Topics: Animals; Animals, Newborn; Antihypertensive Agents; Azepines; Endothelin-1; Glucose Tolerance Test; Hypertension; Hypertriglyceridemia; Insulin; Male; Muscle Contraction; Muscle, Smooth, Vascular; Oligopeptides; Piperidines; Potassium Chloride; Rats; Rats, Wistar