| 1. |
- Fugmann, Andreas, et al.
(författare)
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Central and peripheral haemodynamic effects of hyperglycaemia, hyperinsulinaemia, hyperlipidaemia or a mixed meal
- 2003
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 105:6, s. 715-721
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to evaluate the haemodynamic changes during hyperinsulinaemia, hyperglycaemia or hypertriglyceridaemia in relation to those following a mixed meal. Ten subjects were subjected to hypertriglyceridaemia (3.9 mmol/l) for 2 h by an infusion of Intralipid and heparin. Nine subjects received a hyperglycaemic clamp (12.5 mmol/l) with octreotide and low-dose insulin infusion to maintain normoinsulinaemia (10 m-units/l). Ten subjects received saline for 2 h as a control and, thereafter, 2 h of normoglycaemic hyperinsulinaemic clamp (80 m-units/l). Finally, ten subjects were evaluated for 2 h following an ordinary mixed meal. Calf blood flow was measured by venous occlusion plethysmography and cardiac index by thoracic bioimpedance. Both the mixed meal and normoglycaemic hyperinsulinaemia lowered total peripheral resistance, and increased calf blood flow and cardiac index, whereas blood pressure decreased (P <0.05-0.001). Both hyperglycaemia and hypertriglyceridaemia increased calf blood flow, but blood pressure was unchanged. Total peripheral resistance was unchanged in hypertriglyceridaemia, whereas hyperglycaemia induced a significant increase. Normoglycaemic hyperinsulinaemia induced a haemodynamic pattern similar, but to a lesser extent, to the pattern seen following a mixed meal. Hyperinsulinaemia seems to be a major mediator of the haemodynamic response, but other factors are obviously also of great importance. Hypertriglyceridaemia and hyperglycaemia induced haemodynamic responses that are not similar to those seen following a mixed meal.
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| 2. |
- Holmlund, A., et al.
(författare)
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Soluble intercellular adhesion molecule-1 is related to endothelial vasodilatory function in healthy individuals
- 2002
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Ingår i: Atherosclerosis. - 0021-9150 .- 1879-1484. ; 165:2, s. 271-276
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the associations between markers of systemic and vascular inflammation, and indicators of vascular morphology and function. METHODS: In 59 apparently healthy individuals, we measured serum levels of highly sensitive C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Endothelium-dependent (EDV) and -independent (EIDV) vasodilatation was evaluated in the forearm by venous occlusion plethysmography and local infusions of methacholine and sodium nitroprussid. Endothelial function index (EFI) was expressed as the EDV/EIDV ratio. The intima-media thickness (IMT) of the common carotid artery was investigated with ultrasound (far wall). RESULTS: EFI was inversely related only to ICAM-1 (r=-0.31, P<0.02) by univariate analysis. This association remained significant after adjustment for age, sex, blood pressure, smoking and serum cholesterol. EFI did not relate to hsCRP, VCAM-1 or E-selectin. Neither hsCRP, nor the adhesion molecules were significantly related to carotid artery IMT. CONCLUSION: ICAM-1 was related to endothelial vasodilatory function, but not to IMT, suggesting that endothelial inflammatory activation is related to an impaired vascular relaxation in apparently healthy individuals.
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| 3. |
- Kurland, Lisa, 1960-, et al.
(författare)
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Polymorphisms in the renin-angiotensin system and endothelium-dependent vasodilation in normotensive subjects
- 2001
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Ingår i: Clinical Physiology. - : Wiley. - 0144-5979 .- 1365-2281. ; 21:3, s. 343-349
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Our aim was to test the hypothesis that genes encoding components in the renin-angiotensin system influence endothelial vasodilatory function. METHODS: In 59 apparently healthy, normotensive individuals, endothelium-dependent vasodilation (EDV) and endothelial-independent vasodilation (EIDV) was evaluated by infusing metacholine and sodium nitroprusside into the brachial artery. Forearm blood flow was measured by venous occlusion plethysmography. The ACE insertion (I)/deletion (D) polymorphism, the T174M and M235T angiotensinogen restriction fragments length polymorphisms, the angiotensin II receptor type 1 (AT1R) A1166C, and the aldosterone synthase gene (CYP11B2) C-344T polymorphisms were analysed. RESULTS: When analysing the ACE, the two angiotensinogen and the aldosterone synthase CYP11B2 genotypes independently, no significant association with endothelial vasodilatory function was found. However, a significant reduction in endothelium-dependent vasodilation was observed in the subjects (n=9) with the ACE D allele and the angiotensinogen T174M genotype (P<0.05). Subjects with the AT1R genotype AC showed a reduction in both EDV (P=0.05) and EIDV (P=0.04) when compared with those with the AA genotype. CONCLUSIONS: The subjects with the ACE D allele in combination with the angiotensinogen T174M genotype are associated with a reduced EDV. This together with the observation that the AC AT1R genotype is associated with a reduction in both EDV and EIDV, supports the hypothesis that endothelial vasodilatory function is influenced by genes in the renin-angiotensinogen system.
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| 4. |
- Lind, Lars, et al.
(författare)
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Ageing impairs insulin-mediated vasodilatation but not forearm glucose uptake
- 2001
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 31:10, s. 860-864
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is unclear if insulin-mediated vasodilatation is altered by ageing and if this affects insulin-mediated glucose uptake. MATERIAL AND METHODS: A 2-h euglycaemic hyperinsulinaemic clamp (56 mU m(-2) min(-1)) was performed in 10 healthy, nonobese elderly men (70-75 years) and 13 young men (23-28 years). Forearm blood flow (FBF) was measured by venous occlusion plethysmography and forearm glucose uptake was calculated by arterial and venous serum glucose determinations in the forearm. RESULTS: Insulin induced an increase in FBF in the younger men (from 3.9 +/- 1.1 SD to 5.9 +/- 2.2 mL min(-1) 100(-1)mL tissue, P < 0.001), but this insulin-mediated vasodilatation was completely blunted in the elderly subjects. Glucose extraction during the clamp was significantly higher in the elderly subjects (1.2 +/- 0.76 vs. 0.82 +/- 0.37 mmol L(-1) at 120 min, P < 0.01), resulting in a similar forearm glucose uptake in the two groups. On the other hand, whole-body glucose uptake was significantly decreased in the elderly subjects (5.3 +/- 1.8 vs. 8.0 +/- 1.1 mg kg(-1) min(-1), P < 0.001). CONCLUSION: The present study showed that the ability of insulin to induce vasodilatation is blunted in the forearm in healthy, nonobese elderly subjects. However, the elderly compensate for this impairment with an increased glucose extraction from arterial blood to maintain an unaltered forearm glucose uptake.
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| 5. |
- Lind, Lars, et al.
(författare)
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Endothelium-dependent vasodilation in hypertension : a review
- 2000
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Ingår i: Blood Pressure. - 0803-7051 .- 1651-1999. ; 9:1, s. 4-15
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Tidskriftsartikel (refereegranskat)abstract
- Using both in vitro and in vivo techniques, it has repeatedly been shown that endothelium-dependent vasodilation (EDV) is impaired in different forms of experimental hypertension (SHR, Dahl salt-sensitive rat, DOCA-salt rat and renovascular hypertension). EDV has also been found to be impaired in primary, as well as in secondary forms of human hypertension. Although impaired EDV is a general finding in hypertension, the pathophysiological mechanisms might differ between different forms of hypertension and between different types of vessels and vascular beds. Impaired activity of nitric oxide synthase, increased release of endothelin-1, increased production of a prostanoid-derived contracting factor, decreased generation of endothelium-derived hyperpolarizing factor/s and impairment caused by superoxide ions have all been shown to contribute to the impairment of EDV during different conditions. While most antihypertensive treatments improve EDV in experimental hypertension, no uniform picture has been seen in human hypertension, possibly because different antihypertensive drugs have different direct actions on EDV. This review shows that while impaired EDV has been found to be a general feature of hypertension, the mechanisms involved and the therapeutic opportunities have still to be established.
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| 6. |
- Lind, Lars, et al.
(författare)
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Endothelium-dependent vasodilation is impaired in apparently healthy subjects with a family history of myocardial infarction
- 2002
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Ingår i: Journal of Cardiovascular Risk. - : Oxford University Press (OUP). - 1350-6277 .- 1473-5652. ; 9:1, s. 53-57
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate whether endothelial-dependent vasodilation is altered in healthy subjects with a family history of myocardial infarction. SETTING: Tertiary University Hospital SUBJECTS AND DESIGN: Fifty apparently healthy subjects selected from the general population were subjected to an evaluation of endothelial-dependent vasodilation (EDV) and endothelial-independent vasodilation (EIDV) by means of local infusion of methacholine (MCh, 2 and 4 microg/min) and sodium nitroprusside (SNP, 5 and 10 microg/min) with measurements of forearm blood flow with venous occlusion plethysmography. The occurrence of plaque and the intima-media thickness of the carotid arteries were determined by ultrasonography. RESULTS: Subjects reporting at least one parent suffering from myocardial infarction (n = 11) showed a significantly lower EDV than subjects without such a family history (21 +/- 3.7 vs. 26 +/- 6.7 ml/min/100 ml tissue at MCh 4 microg/min, P<0.05). EIDV was not significantly different between the groups (21 +/- 6.8 vs. 18 +/- 5.4 ml/min/100 ml tissue at SNP 10 microg/min). Age, sex distribution, body mass index, waist to hip ratio, blood pressure, lipids, fasting blood glucose, smoking habits and status of the carotid arteries were not significantly different between the groups. CONCLUSION: A family history of myocardial infarction was found to be associated with an impaired endothelial-dependent vasodilation in the forearm of apparently healthy subjects. The risk factor profile was not different from the control group, suggesting that genetic factors are responsible for the impaired endothelial-dependent vasodilation.
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| 7. |
- Lind, Lars, et al.
(författare)
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Insulin-mediated vasodilatation, but not glucose uptake or endothelium-mediated vasodilatation, is enhanced in young females compared with males
- 2002
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 102:2, s. 241-246
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Tidskriftsartikel (refereegranskat)abstract
- In order to evaluate possible differences between men and women with regard to the ability of insulin to induce vasodilatation, promote glucose uptake and enhance endothelium-dependent vasodilatation, 12 young (22-28 years), non-obese women and 15 corresponding males were subjected to 2 h of euglycaemic hyperinsulinaemia (insulin infusion rate of 56 m-units x min(-1) x m(-2)). Forearm blood flow was measured by venous occlusion plethysmography. Endothelium-dependent vasodilatation was evaluated by the local intra-arterial infusion of methacholine into the brachial artery (2-4 microg/min). The cardiac index was measured by thoracic bioimpedance. A 2 h period of hyperinsulinaemia increased the plasma insulin concentration to a similar degree in both sexes (females, 84 +/- 8.8 m-units/l; males, 87 +/- 7.5 m-units/l), but induced a more marked increase in forearm blood flow in females than in males (+104 +/- 67% and +52 +/- 30% respectively; P<0.01; 95% confidence interval for difference 11-94%). Furthermore, a significant decrease in total peripheral resistance (-20 +/- 6.9%; P<0.01) and an increase in cardiac index (+23 +/- 13%; P<0.01) were seen in women only (P<0.05 compared with men). Blood pressure and heart rate were not altered in either sex. Whole-body insulin-mediated glucose uptake and forearm glucose uptake did not differ between the sexes, and the ability of insulin to enhance endothelium-dependent vasodilatation (+19%; P<0.01) was similar in men and women. In conclusion, the present study shows that the ability of insulin to cause vasodilatation was greater in non-obese young women compared with men. However, no differences between the sexes were seen with regard to insulin-mediated glucose uptake and the ability of insulin to enhance endothelium-dependent vasodilatation.
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| 8. |
- Lind, Lars, et al.
(författare)
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The effect of smoking on endothelial vasodilatory function evaluated by local infusion of metacholine in the forearm is dependent on the duration of smoking
- 2003
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Ingår i: Nicotine & tobacco research. - : Oxford University Press (OUP). - 1462-2203 .- 1469-994X. ; 5:1, s. 125-130
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the study was to evaluate if endothelial vasodilatory function in the human forearm is impaired by regular cigarette smoking. The setting was a tertiary university hospital. Subjects were 56 apparently healthy subjects from a population screening (mean age 50) and 52 young healthy volunteers (mean age 25) who were investigated regarding endothelial-dependent (EDV) and endothelial-independent vasodilation (EIDV) by means of local infusion of metacholine (MCh; 2 and 4 mg/min) and sodium nitroprusside (SNP; 5 and 10 mg/min) in the forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The MCh to SNP FBF ratio was denoted the endothelial function index. In the young subjects, no differences between smokers (n = 12) and non-smokers regarding EDV or EIDV were seen. In the population sample, however, the smokers (n = 8) showed an attenuated endothelial function index when compared with non-smokers (1.0 +/- 0.1 vs. 1.3 +/- 0.3, p = .02). The EDV showed a significant inverse relationship to the duration of smoking (r = -0.52, p < .05), independent of age, when the smokers in both groups were analyzed together. A similar, although not significant, relation was found between the endothelial function index and the duration of smoking (p = -.44). The present study showed that endothelial vasodilatory function was impaired in middle-aged, but not young, smokers, suggesting that the duration of smoking is of major importance for the deleterious effects of smoking on endothelial vasodilatory function.
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| 9. |
- Lind, Lars, et al.
(författare)
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The impairment in endothelial function induced by non-esterified fattyacids can be reversed by insulin
- 2000
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 99:3, s. 169-174
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Lind, Lars, et al.
(författare)
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The types of circulating fatty acids influence vascular reactivity
- 2002
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Ingår i: Lipids. - : Wiley. - 0024-4201 .- 1558-9307. ; 37:12, s. 1141-1145
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to investigate the relationship between the composition of FA in serum lipids, a marker of dietary fat intake, and vascular reactivity using a combination of cross-sectional and intervention approaches. Fifty-six middle-aged subjects were evaluated in a cross-sectional protocol regarding the relationship between the proportion of FA in serum cholesterol esters and vascular reactivity using measurements of forearm blood flow (FBF) with venous occlusion plethysmography during hyperemia. Another 19 middle-aged subjects were given a rapeseed oil-based diet rich in mono- and polyunsaturated FA or a control diet rich in saturated FA during two consecutive 4-wk periods separated by a 4-wk washout period. In the cross-sectional protocol, the FA 18:0 and 20:3 were positively related to resting FBF, whereas an inverse relationship was seen for the FA 20:5 and 22:6 (P < 0.05-0.01). Opposite relationships were seen between these four FA and the relative increase in maximal FBF during hyperemia (P < 0.05-0.01). In the intervention protocol, the saturated diet increased resting FBF, as well as the relative increase in maximal FBF during reactive hyperemia, compared to the diet rich in unsaturated FA (P < 0.05). Both the cross-sectional and intervention data support the view that the composition of serum FA, which at least partly reflects the quality of dietary fat, plays a role in determinations of vascular reactivity.
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