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PubMed2000

The impairment in endothelial function induced by non-esterified fatty acids can be reversed by insulin.

Dyslipidaemia, with elevations of circulating triacylglycerols (triglycerides) and non-esterified (free) fatty acids, and hyperinsulinaemia are often found in the same subjects, the so-called 'insulin resistance syndrome'. The present study aims to investigate how elevated levels of non-esterified fatty acids, hyperinsulinaemia and the combination of these factors affects endothelium-dependent vasodilatation (EDV). Ten volunteers were examined on two occasions. Intralipid (plus heparin) or saline (0.9% NaCl) was infused for 4 h. During the final 2 h, euglycaemic hyperinsulinaemia (80+/-4 m-units/l) was imposed. EDV and endothelium-independent vasodilatation were evaluated in the forearm by local intra-arterial infusion of methacholine or sodium nitroprusside at baseline and after 2 and 4 h. Forearm blood flow was measured by venous occlusion plethysmography. Lipid oxidation was determined by measuring plasma malondialdehyde levels. Infusion of Intralipid plus heparin increased the concentration of non-esterified fatty acids to 2.6+/-1.2 mmol/l and decreased EDV from 27.6+/-8.7 to 21.0+/-5.7 ml x min(-1) x 100 ml(-1) tissue (P < 0.01). This effect was completely reversed by hyperinsulinaemia (P < 0.01). Hyperinsulinaemia alone increased EDV (to 30.4+/-9.5 ml x min(-1) x 100 ml(-1) tissue; P < 0.01), while endothelium-independent vasodilatation was unaltered by the interventions. Infusion of Intralipid plus heparin increased malondialdehyde levels from 0.67+/-0.22 to 1.2+/-0.37 micromol/l (P < 0.001), while hyperinsulinaemiadid not change the malondialdehyde level. In conclusion, an acute increase in serum levels of non-esterified fatty acids increased lipid oxidation and decreased EDV. The effect on EDV of non-esterified fatty acids could be reversed by hyperinsulinaemia.

Adult↗
PubMed2004

Aging, physical fitness and endothelial function: are all ultracentenarians marathon runners?

This comment focuses on the background and implications of a study published in this issue of Clinical Science by Franzoni and colleagues showing that physical training improves nitric oxide availability and microvascular distensibility not only in young, but also in elderly, individuals. The main features of the study as well as its potential limitations will be also highlighted.

Aged↗
PubMed2004

Lack of effect of oral glucose loading on conduit vessel endothelial function in healthy subjects.

The aim of the present study was to investigate the impact of an oral glucose load on circulating insulin and glucose levels and arterial function in healthy non-diabetic subjects. Thirty-nine non-obese, healthy subjects (24 female, 15 male), aged 21.0+/-1.8 years of age, were randomly assigned to undergo either an OGTT (oral glucose tolerance test; 75 g of glucose) or administration of a placebo. Analyses of lipids, liver function and HbA(1c) (glycated haemoglobin) at baseline revealed results which were within the standard reference range. Insulin and glucose levels as well as vascular function [FMD (flow-mediated dilation)] were measured at 0, 60 and 120 min. Compared with baseline, the control subjects did not exhibit any significant changes in glucose or insulin levels, whereas, in the OGTT group, blood glucose levels at both 60 (5.4+/-1.7 mmol/l) and 120 (5.0+/-1.1 mmol/l) min increased significantly relative to baseline (4.1+/-0.4 mmol/l; both P<0.001) and, similarly, insulin levels were higher at both 60 (30.1+/-21.3 m-units/l) and 120 (34.9+/-23.6 m-units/l) min compared with baseline (4.7+/-4.3 m-units/l; both P<0.001). Although blood glucose and insulin levels changed, FMD did not significantly differ between time-points or between groups. In summary, despite significantly elevated glucose and insulin concentrations in these subjects, we observed no change in vascular function, suggesting that acute elevations of glucose and insulin within the clinically normal range are not associated with impaired vascular function in vivo.

Administration, Oral↗
PubMed2006

Maternal undernutrition reduces aortic wall thickness and elastin content in offspring rats without altering endothelial function.

Epidemiological studies suggest a link between fetal/early infant nutrition and adult coronary artery disease. In the present study, we examined the effects of altering nutrition during gestation, lactation and juvenile life on aortic structure and function in rats. Wistar rat dams were fed either a control or low-protein diet throughout pregnancy, or a low-protein diet for the final 7 days of gestation only. At 21 days post-partum, male pups were weaned on to a control, low-protein or high-fat diet. At 12 weeks, the offspring rats were killed. In 46 rats, aortic sections were mounted and stained to assess media thickness and elastin content. In a further 38 rats, aortic rings were suspended in an organ bath and vascular reactivity was tested with dose-response curves to the endothelium-dependent dilator acetylcholine and the endothelium-independent dilator sodium nitroprusside. Rats exposed to maternal protein restriction while in utero had a significantly decreased aortic wall thickness compared with control rats (P=0.005). Total elastin content of the aorta was also decreased by both maternal low-protein (P=0.02) and early postnatal low-protein (P=0.01) diets. Neither maternal nor postnatal low-protein or high-fat diets, however, resulted in any significant changes in arterial dilator function. In conclusion, fetal undernutrition in rats, induced via a maternal low-protein diet, causes a decrease in aortic wall thickness and elastin content without altering aortic dilator function. These changes in vascular structure may amplify aging-related changes to the vasculature and contribute to the pathophysiology of the putative link between impaired fetal growth and adult cardiovascular disease.

Animal Nutritional Physiological Phenomena↗
PubMed2003

Physiological testosterone replacement and arterial endothelial function in men.

OBJECTIVE: The vascular effects of fluctuations in testosterone levels within the physiological range in otherwise healthy men are not known. We therefore aimed to study arterial function in hypogonadal men receiving long-term physiological androgen replacement therapy, at trough and peak testosterone levels. PATIENTS AND DESIGN: We recruited nine hypogonadal men (aged 35 +/- 4 years) receiving androgen replacement therapy, each treated with 800 mg testosterone (T) depot preparations every 6 months. MEASUREMENTS: Serum lipid and hormone levels and arterial reactivity were measured, prior to (trough T) and 2-4 weeks following testosterone administration (peak T). Each subject therefore served as their own control. Vessel diameter was measured by ultrasound at rest, during reactive hyperaemia [leading to flow-mediated dilatation (FMD), an endothelium-dependent response] and after sublingual nitroglycerin (GTN, an endothelium-independent dilator). RESULTS: Serum T (13 +/- 2 nmvs. 27 +/- 3 nm for trough and peak serum T, respectively, P < 0.001; normal adult male range 11-35 nm), and free T (195 +/- 23 pmvs. 510 +/- 93 pm, P < 0.005) significantly increased following subcutaneous depot T administration, as did serum oestradiol (100 +/- 10 pmvs. 175 +/- 9 pm, P = 0.001; normal adult male range < 250 pm). There was a significant decrease in FMD (3.6 +/- 1.1%vs. 3.0 +/- 0.8%, P < 0.01), but GTN responses were similar (9.5 +/- 0.8%vs. 10.4 +/- 1.0%, P > 0.2). Lipid, blood pressure and vessel diameter measurements were also similar before and after testosterone administration. CONCLUSION: Physiological replacement of testosterone is associated with decreased endothelium-dependent dilatation, in hypogonadal men.

Adult↗
PubMed1999

Myocardial protection during cardiac surgery from the viewpoint of coronary endothelial function.

1. During cardiac surgery, the heart is arrested and subject to ischaemia-reperfusion injury. 2. To protect the heart, cardioplegia is usually used to initially stop and then maintain the still condition of the heart, which not only facilitates the precise operation but, more importantly, minimizes the energy consumption of the heart during this period. 3. The ischaemia-reperfusion injury may involve both myocytes and coronary endothelium-smooth muscle and, therefore, the protection of the heart should also involve these two aspects. 4. Injury to the heart involves: (i) ischaemia-reperfusion injury to the myocytes and coronary circulation; and (ii) possible injury to the coronary circulation by cardioplegia due to its hyperkalaemic components. 5. Injury to the coronary circulation may involve both endothelium-derived nitric oxide (EDNO) and endothelium-derived hyperpolarizing factor (EDHF) mechanisms. The EDNO mechanism is susceptible to ischaemia-reperfusion, whereas the EDHF mechanism may be altered by hyperkalaemic cardioplegia. 6. To further protect the heart, supplemental therapy for EDNO and optimizing the components of cardioplegia to restore the EDHF mechanism may be important.

Animals↗
PubMed2002

Endothelial function in healthy younger and older hyperhomocysteinemic subjects.

OBJECTIVES: To compare endothelium-dependent vasomotor response in healthy younger and older subjects without classic cardiovascular risk factors, with high and normal fasting homocysteine (tHcy) levels. DESIGN: We compared endothelium-dependent vasodilatation, using ultrasound, in healthy younger (aged 18-40) and older (> or =70) people with normal (<13 micromol/L) and high (>15 micromol/L) tHcy levels. Exclusion criteria were smoking, personal history of cardiovascular disease, hypertension, chronic diseases, vitamin intake, obesity, abnormal serum lipids levels, and creatinine higher than 130 micromol/L. SETTING: Research laboratory. MEASUREMENTS: In addition to tHcy levels, serum folate and vitamin B12 levels were measured. RESULTS: We studied 17 younger and 12 older hyperhomocysteinemic subjects and respective aged-matched normohocysteinemic subjects. Endothelium-dependent vasodilatation was lower in the hyperhomocysteinemic older people (P <.01) than in all younger subjects and in normohomocysteinemic older people. Serum vitamin B12 levels were higher in younger and older normal controls. Folic acid levels were higher in younger controls and in both older groups. CONCLUSIONS: This study shows an effect of high circulating tHcy on vascular reactivity in older people. Because serum levels of tHcy are associated with nutritional status of vitamin B12 and folic acid, prospective studies are necessary to demonstrate the effects of a long-term nutritional supplementation with vitamins on vascular function and global cardiovascular risk.

Adolescent↗
PubMed2002

Effect of troglitazone on endothelial function in type 2 diabetic patients.

Lysophosphatidylcholine (lysoPC), a component of oxidized low-density lipoprotein cholesterol (LDL-C), has been reported to impair nitric oxide production and endothelium-dependent vasorelaxation. The effects of troglitazone (CAS 97322-87-7), which is an antidiabetic agent with antioxidant properties, on serum levels of lysoPC and nitrite/nitrate (NOx) have been studied. Eight patients with Type 2 diabetes (non-insulin dependent diabetes mellitus, NIDDM) were studied (age: 61.5 +/- 2.8 years; diabetes duration: 10.2 +/- 1.6 years). They were additionally given troglitazone (200 mg once daily) since their fasting plasma glucose (FPG) and HbA1c levels had been increased in spite of conventional medications. Before and after 12 weeks of treatment with troglitazone their blood pressure, FPG, HbA1c, lipid profiles and NOx were measured. Troglitazone treatment had a slight depressor effect (decreasing the blood pressure from 133 +/- 5/72 +/- 3 to 127 +/- 4/68 +/- 1 mmHg; p < 0.05). FPG and HbA1c were significantly decreased with the therapy (181 +/- 10 to 160 +/- 10 mg/dl; p < 0.05 and 9.1 +/- 0.6 to 8.1 +/- 0.5%; p < 0.05, respectively). In contrast, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and LDL-C were maintained within normal limits throughout the study. Although lysoPC and NOx levels were not altered, a negative correlation between lysoPC and NOx levels was observed. These results suggest that troglitazone is a beneficial agent improving FPG and HbA1c levels in NIDDM patients, while its effects on serum lysoPC and NOx levels, at least for 12 weeks, seem to be minimal.

Aged↗