| 1. |
- Lind, Lars, et al.
(författare)
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Endothelium-dependent vasodilatation in treated and untreated hypertensive subjects
- 1999
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 8:3, s. 158-164
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Tidskriftsartikel (refereegranskat)abstract
- It has repeatedly been shown that endothelium-dependent vasodilatation (EDV) is impaired in patients with untreated hypertension. The effect of antihypertensive treatment on EDV has, however, not been extensively investigated. In the present study, EDV and endothelium-independent vasodilatation (EIDV) were studied in 20 untreated and 41 treated hypertensive subjects and in 26 matched, normotensive controls by means of infusion of methacholine (MCh), 2 and 4 microg/min, evaluating EDV, and nitroprusside (SNP), 5 and 10 microg/min, evaluating EIDV, in the brachial artery. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The vasodilatory action of MCh was impaired in untreated hypertensives compared with controls, with the response in the treated hypertensives in between the other two groups (p < 0.01 vs both of the other groups). EIDV, on the other hand, was enhanced in the treated hypertensives (p < 0.01), so that the MCh to SNP FBF ratio, an index of endothelial function, was attenuated in both treated and untreated hypertensives (0.97 +/- 0.24 and 0.96 +/- 0.15, respectively), compared with controls (1.27 +/- 0.29, p < 0.001). Both EDV and EIDV declined with increasing number of antihypertensive drugs used in the treated hypertensives (p < 0.05). In conclusion, the endothelial function index was found to be similarly depressed in both treated and untreated hypertensive subjects compared with normotensive controls. Antihypertensive therapy seems to improve the vasodilatory capacity in general rather than enhancing endothelial function.
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| 2. |
- Lind, Lars, et al.
(författare)
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Endothelium-dependent vasodilation and structural and functional changes in the cardiovascular system are dependent on age in healthy subjects
- 1999
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Ingår i: Clinical Physiology. - : Wiley. - 0144-5979 .- 1365-2281. ; 19:5, s. 400-409
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate possible associations between endothelium-dependent vasodilatation (EDV) and cardiovascular structure and function. EDV could influence peripheral resistance and be affected by atherosclerosis and might thereby influence indices of cardiovascular structure and function. In a group of 31 apparently healthy men and 25 women (age range 20-69 years), EDV was evaluated by infusion of metacholine (4 micrograms min-1), and endothelium-independent vasodilatation (EIDV) was assessed by nitroprusside infusion (SNP, 10 micrograms min-1) in the brachial artery. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Left ventricular (LV) geometry and function and the intima-media thickness in the carotid artery were assessed by ultrasonography. The stroke index to pulse pressure ratio was used to evaluate arterial compliance. Several indices of cardiovascular structure and function were found to be related to an index of endothelial function, the EDV to EIDV ratio. Furthermore, left ventricular mass (LVM), the atrio-ventricular plane displacement, E/A ratio, IVRT, the intima-media thickness of the carotid artery and arterial compliance were all significantly related to both EDV and EIDV in women. However, most indices of cardiovascular structure and function, as well as endothelial function, change with age and only the relation between LV diastolic function and endothelial function in men remained significant (P < 0.05) after including age in multiple regression analysis. Age was related to both cardiovascular structure and function, as well as to endothelial function. Multiple regression analysis showed that ageing generally affects cardiovascular characteristics and endothelial function in parallel in these healthy subjects.
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| 3. |
- Sarabi, Mahziar D.
(författare)
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Cardiovascular risk factors and endothelium-dependent vasodilation
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The vascular endothelium is a major modulator of vascular structur and function. This thesisincludes clinical studies investigating the associations between cardiovascular risk factors andendothelium-dependent vasodilation (EDV) in the human forearm vascular bed.A progressive decline in EDV with advancing age was found in men, while this decline wasevident only after the menopause in women. In men, but not in women, metabolic factors likefasting blood glucose and waist/hip ratio were independent predictors of EDV.Serum HDL-cholesterol, unsaturated fatty acids and vitamin E were all positively associatedwith EDV, while serum LDL-cholesterol and saturated fatty acids were negative predictors ofEDV.Cigarette smoking induced a dose-dependent attenuation in EDV in young healthy subjects,being maximal shortly after initiation of smoking and persisting up to 30-50 minutes. Alsonicotine chewing gum induced a similar impairment in EDV. Both serum nicotine levels andblood pressure were independent predictors of EDV.Mental stress induced by an arithmetic task selectively attenuated EDV in young healthysubjects, while two painful stress test, cold pressure and isometric handgrip test, induced amore general impairment in vasodilation.An ordinary mixed meal induced a transient decline in EDV in young healthy individuals,which was associated with postprandial levels of free fatty acids in serum.In conclusion, aging induced a progressive impairment in EDV in men, probably mediated bymetabolic factors. In women, the endothelium was protected against such impairment until theage of menopause. HDL-cholesterol, vitamin E and unsaturated fatty acids were positivepredictors and LDL-cholesterol and saturated fatty acids were negative predictors of EDV.Smoking, nicotine chewing gum and mental stress impaired EDV, while an ordinary mixedmeal only transiently impaired EDV.
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| 4. |
- Sarabi, Mahziar, et al.
(författare)
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Effects of age, gender and metabolic factors on endothelium-dependent vasodilation : a population-based study
- 1999
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 246:3, s. 265-274
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: A progressive decline in endothelium-dependent vasodilation (EDV) in the human forearm with age has previously been reported. The aim of this study was to evaluate the interplay between age, gender and metabolic factors on EDV in healthy subjects in a population-based study. SETTING: Tertiary university hospital. SUBJECTS AND DESIGN: Thirty-six healthy men and 30 women, aged 20-69 years, underwent measurements of forearm blood flow (FBF) at rest and during local infusions of 2 and 4 microg min-1 of metacholine (evaluating EDV) and 5 and 10 microg min-1 of sodium nitroprusside (evaluating endothelium-independent vasodilation, EIDV) and during reactive hyperaemia by venous occlusion plethysmography. RESULTS: Age was inversely related to EDV (r = - 0.41, P < 0.05 in men; r = - 0.61, P < 0.01 in women) and maximal FBF during reactive hyperaemia in both men and women. EIDV was significantly related to age in an inverse way in women only. EDV was more pronounced in females than in males before menopause (48 +/- 3 SD years, 635 +/- 186 vs. 502 +/- 269% in males, P < 0.05), but similar in women and men thereafter (374 +/- 141 vs. 370 +/- 185% in men). The slope of the regression line for the relationship between age and EDV was flatter in premenopausal than in postmenopausal women (- 2.3 vs. - 6.4), whilst this slope was similar in younger and older men (- 5.5 vs. - 5.3). In multiple regression analysis, fasting blood glucose levels and the waist/hip ratio remained the only significant predictors of EDV in men (P < 0.01 for both), whilst age was the only significant independent predictor of EDV in women (P < 0.01). CONCLUSION: The interplay between age and metabolic factors as determinants of endothelial function is different in healthy men and women.
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| 5. |
- Sarabi, Mahziar, et al.
(författare)
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Endothelin plays an important role in the endothelium-dependent vasodilatation in the human forearm
- 1999
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 59:1, s. 17-22
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Tidskriftsartikel (refereegranskat)abstract
- Endothelium-dependent vasodilatation (EDV) in humans has been evaluated mainly by local infusion of a muscarinic-receptor agonists in the forearm. It has been postulated that the function of the vasodilator nitric oxide (NO) can be evaluated with this technique. However, the role of the vasoconstrictor endothelin in this model has not been investigated. METHODS: Ten male hypertensive and seven male normotensive subjects were subjected to measurements of forearm blood flow (FBF) by venous occlusion plethysmography during local intra-arterial infusion of metacholine (4 microg/min) or nitroprusside (10 microg/min). In parallel, forearm venous plasma endothelin (ir-ET) was determined. RESULTS: Metacholine and nitroprusside increased FBF 2.3 and 2.2 times the baseline level (6.6+/-2.8 SD ml/min/100 ml tissue) in hypertensive subjects and 5.1 times the baseline level (2.7+/-3.0 ml/min/100 ml tissue) for both drugs in the normotensive subjects. None of the drugs induced any significant changes in ir-ET levels in any of the groups (baseline 1.5+/-0.4 pmol/l in hypertensive and 1.1+/-1.2 pmol/l in normotensive subjects). However, in the hypertensive subjects, the individual change in venous ir-ET levels during infusion with metacholine, but not with nitroprusside, was inversely related to the degree of vasodilatation induced by this agent (r = -0.71, p < 0.02). A similar correlation coefficient (r=-0.69) was found in healthy subjects. CONCLUSION: Muscarinic-receptor-agonist-stimulated vasodilatation in the human forearm, thought mainly to reflect NO synthesis, was inversely related to the change in endothelin levels, suggesting an important role for this endothelium-derived vasoconstrictor in this model of EDV.
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| 6. |
- Sarabi, Mahziar, et al.
(författare)
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Local vasodilatation with metacholine, but not with nitroprusside, increases forearm glucose uptake
- 1999
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Ingår i: Physiological Research. - 0862-8408 .- 1802-9973. ; 48:4, s. 291-295
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Tidskriftsartikel (refereegranskat)abstract
- Insulin is known to increase blood flow in parallel to glucose uptake in skeletal muscle. However, it is not known if an increase in blood flow by itself is associated with an increase in glucose uptake in the absence of hyperinsulinemia. To investigate further this matter, the effect of increased blood flow on forearm glucose uptake was studied in the fasting state during intra-arterial infusions of two different vasodilators, metacholine and nitroprusside, in 19 hypertensive subjects. Both metacholine (4 microg/min) and nitroprusside (10 microg/min) increased resting forearm blood flow, measured by venous occlusion plethysmography, to a similar degree (180 % and 170 %, respectively, p<0.0001 for both). However, metacholine infusion increased the forearm glucose uptake from 2.0+/-0.9 (S.D.) during rest to 5.5+/-3.0 umol/min/100 ml tissue (p<0.0001), while no significant change in glucose uptake was seen during nitroprusside infusion (2.3+/-1.4 micromol/min/100 ml tissue). In conclusion, vasodilatation induced by metacholine, but not by nitroprusside, increased glucose uptake in the forearm of hypertensive patients. Thus, an increase in forearm blood flow does not necessarily improve glucose uptake in the forearm during the fasting state.
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| 7. |
- Sarabi, Mahziar, et al.
(författare)
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Relationships between Endothelium-Dependent Vasodilation, Serum Vitamin E and Plasma Isoprostane 8-Iso-PGF2alpha Levels in Healthy Subjects
- 1999
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Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 36:6, s. 486-491
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Tidskriftsartikel (refereegranskat)abstract
- Due to the reported associations between a low intake of vitamin E and atherosclerosis on one hand, and between endothelial dysfunction and atherosclerosis on the other hand, we investigated the relationship between endothelium-dependent vasodilation and serum levels of vitamin E (alpha- and gamma-tocopherol) as well as the lipid peroxidation markers malondialdehyde and 8-iso-PGF(2alpha) in a healthy population. Healthy subjects (31 men and 25 women), aged between 20 and 69 years, underwent measurements of forearm blood flow (FBF) at rest and during local infusion of 2 and 4 microg/min of methacholine (Mch, to evaluate endothelium-dependent vasodilation) and 5 and 10 microg/min of sodium nitroprusside (SNP, to evaluate endothelium-independent vasodilation, and during reactive hyperemia using venous occlusion plethysmography. Serum alpha-tocopherol concentration was significantly related to the index of endothelial function (r = 0.46, p < 0.01), defined as the ratio between the maximal dilatations during Mch and SNP infusions. Serum gamma-tocopherol levels were positively related to the maximal FBF during reactive hyperemia (r = 0.54, p < 0.01) in women only. Furthermore, in women only, plasma 8-iso-PGF(2alpha) levels were inversely related to the relative increases in FBF during both Mch and SNP infusions (r = -0.58 and r = -0.59, p < 0.01 for both). The results show a relationship between the levels of alpha-tocopherol and endothelial vasodilatory function, suggesting a beneficial role for this potent lipid-soluble antioxidant also in a population sample of apparently healthy subjects. Furthermore, in women, the accumulation of lipid peroxidation products such as 8-iso-PGF(2alpha) seems to be associated with an impaired vasodilation in general.
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