Mahziar Sarabi

Endothelium-dependent vasodilation is related to the fatty acid composition of serum lipids in healthy subjects

The fatty acid (FA) composition of the serum lipids has been associated with cardiovascular disease (CVD). As an attenuated endothelium-dependent vasodilation (EDV) has been suggested as an early marker of atherosclerosis, we investigated the relationships between the proportion of FA in serum lipids (cholesterol esters and phospholipids) together with the levels of serum LDL- and HDL-cholesterol and triglycerides and EDV, as well as endothelium-independent vasodilation (EIDV). Fifty-six 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 metacholine (Mch, evaluating EDV), 5 and 10 microg/min of sodium nitroprusside (SNP, evaluating endothelium-independent vasodilation, EIDV) using venous occlusion plethysmography. An index of endothelial function was calculated as the ratio between EDV and EIDV. The proportion of palmitic (16:0) and palmitoleic (16:1) acids were inversely related (r=-0.35 and -0.35, P<0.01 for both), while linoleic acid (18:2 n6) and the HDL-cholesterol concentration were positively related (r=0.35 and 0.36, P<0.01 for both) to the endothelial function index. In multiple regression analysis also including age and gender, palmitoleic acid and HDL-cholesterol were significant independent predictors of endothelial function. Alfa-linolenic acid (18:3 n3) was positively correlated to both EDV and EIDV (r=0.40 and 0.43, P<0.01 for both), indicating a protective effect of this essential FA on vasodilation in general. It is concluded that the FA composition of serum lipids, partly reflecting the composition of dietary fat and previously associated with the development of CVD, was associated with endothelial function in apparently healthy subjects.

Effects of age, gender and metabolic factors on endothelium‐dependent vasodilation: a population‐based study

Abstract. Sarabi M, Millgård J, Lind L (University Hospital, Uppsala, Sweden). Effects of age, gender and metabolic factors on endothelium‐dependent vasodilation: a population‐based study. J Intern Med 1999; 246: 265–274.

Mental stress opposes endothelium-dependent vasodilation in young healthy individuals

Mental stress has been shown to induce myocardial ischemia in people with coronary heart disease (CHD), both in the laboratory and in daily life. In order to investigate the role of the endothelium in the regulation of blood flow during stress, the endothelium-dependent (EDV) and endothelium-independent (EIDV) vasodilation was examined in the forearms of healthy people during a mental arithmetic test (MAT), a cold pressor test (CP) and an isometric handgrip test (ISO). A total of 10 young healthy volunteers (four men and six women, aged 20-25 years) underwent measurements of forearm vascular resistance (FVR) during local intra-arterial infusions of methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; inducing EIDV) at rest and during the different forms of stress by the use of venous occlusion plethysmography. MAT induced a significant increase in FVR during MCh infusion (4 mg/min, from 3.5 6 0.7 at rest to 4.2 6 1.4 mmHg/ml per min per 100 ml tissue during MAT; p, 0.01), while FVR during SNP infusion was unchanged by MAT. CP induced a significant increase in FVR during infusions with both MCh and SNP compared to resting levels (p, 0.01 for both), while ISO induced a significant increase in FVR during MCh infusion (p, 0.05) and a smaller increase in FVR during SNP infusion. When the SNP to MCh FVR ratio was used as an index of endothelial function, only MAT impaired endothelial function significantly (p, 0.01). In conclusion, mental stress induced by an arithmetic task selectively opposed EDV in the forearms of young healthy people, while cold pressor and isometric handgrip tests induced a more general attenuation in vasodilatation.

Soluble intercellular adhesion molecule-1 is related to endothelial vasodilatory function in healthy individuals

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.

Short-term effects of smoking and nicotine chewing gum on endothelium-dependent vasodilation in young healthy habitual smokers.

Smoking is a major risk factor for coronary and peripheral vascular disease. This study was designed to investigate the short-term effects of smoking and nicotine gum on endothelium-dependent (EDV) and -independent (EIDV) vasodilation in the forearm of young habitual smokers. In 10 subjects, forearm blood flow (FBF) during local infusion of metacholine (4 microg/min, evaluating EDV) and sodium nitroprusside (10 microg/min, evaluating EIDV) was assessed before and at 10 min (early phase) and 30-50 min (plateau phase) after the initiation of smoking, using forearm venous occlusion plethysmography. Six subjects underwent similar measurements of FBF before and 30 min after chewing a nicotine gum (4 mg). As a change in blood pressure was expected, forearm vascular resistance (FVR) was used to calculate EDV and EIDV. FVR during metacholine infusion increased from 4.6 +/- 1.4 SD to 5.9 +/- 2.1 mm Hg/ml/min/100 ml tissue during the early and to 5.0 +/- 1.6 mm Hg/ml/min/100 ml tissue at the plateau phase of smoking (p < 0.01 for both vs. baseline) and from 4.5 +/- 1.6 to 5.2 +/- 1.6 mm Hg/ml/min/100 ml tissue after chewing the nicotine gum (p < 0.01). No significant changes in EIDV were seen after smoking or the nicotine gum. When all data were analyzed together, plasma nicotine levels and blood pressure were both independent predictors of endothelial function (p < 0.001 for both). In conclusion, cigarette smoking induced a dose-dependent attenuation in EDV, being maximal shortly after initiation of smoking and persisting up to 30-50 min. Nicotine chewing gum induced a similar impairment in EDV.

Captopril, but not nifedipine, improves endothelium-dependent vasodilation in hypertensive patients

The present study aimed to investigate the influence of the angiotensin-converting enzyme (ACE)-inhibitor captopril and the Ca-antagonist nifedipine on endothelium-dependent vasodilation (EDV) in the forearm of hypertensive patients. Twenty-three middle-aged untreated hypertensive patients underwent evaluation of EDV and endothelium-independent vasodilation (EIDV) in the forearm, by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium-nitroprusside (SNP, evaluating EIDV), before and 1 h after intake of either captopril (25 mg) or nifedipine (10 mg) in a randomised, double-blind fashion. A matched normotensive control group was investigated at baseline conditions only. Five of the hypertensives were also evaluated after 3 months of treatment with captopril 25 mg twice daily in an open pilot study.First, the vasodilation induced by methacholine (MCh), but not SNP, was significantly attenuated in the hypertensive patients compared to the normotensive controls (P < 0.001 at mch 4 μg/min).Second, although the two drugs induced a similar decline in blood pressure (BP) 1 h after administration (−11 to 10 mm Hg/−8 to 7 mm Hg), captopril significantly potentiated the vasodilator response to MCh (+32 ± 13%, MCh 4 μg/min, P < 0.01) but not snp, while nifedipine did not significantly alter the response to either mch or snp. the improvement in vasodilator response to mch induced by captopril was closely related to the reduction in bp (r = 0.72, P < 0.01).Third, in the pilot study, 3 months of captopril treatment induced a significant potentiation of the vasodilator response to MCh (+34 ± 17%, MCh 4 μg/min, P < 0.05) in parallel with a significant bp reduction (−22 ± 24/13 ± 13 mm hg, P < 0.05), while the response to snp was unchanged.In conclusion, the present study confirmed that essential hypertension is associated with a defect in EDV. Furthermore, an improvement in EDV was seen in hypertensive patients shortly after administration of captopril, but not nifedipine. In addition, a significant beneficial effect on EDV was seen in a small pilot study during long-term treatment with captopril.

Central and peripheral haemodynamic effects of hyperglycaemia, hyperinsulinaemia, hyperlipidaemia or a mixed meal.

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.

Left Ventricular Hypertrophy is Associated with an Attenuated Endothelium-dependent Vasodilation in Hypertensive Men

To investigate the relationship between left ventricular hypertrophy (LVH) and endothelium-dependent vasodilation (EDV), 30 untreated hypertensive patients, 18 treated hypertensives (53 +/- 7 years, all males) and 26 age-and sex-matched healthy normotensive controls, underwent evaluation of EDV and endothelium-independent vasodilation (EIDV) in the forearm, by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium nitroprusside (SNP, evaluating EIDV). Forearm blood flow was measured by venous occlusion plethysmography and LVH was measured by echocardiography. The reduction in forearm vascular resistance during MCh infusion (4 microg/min) was significantly smaller in the hypertensive patients with LVH when compared to those without LVH, both in the untreated (-61 +/- 12%, n = 19 vs -72 +/- 4%, n = 11, p < 0.01) and in the treated group (-60 +/- 15%, n = 11 vs -75 +/- 5%, n = 7, p < 0.01). Thereby, EDV was significantly impaired only in the hypertensive patients with LVH when compared to controls (-77 +/- 7% at MCh 4 microg/min, p < 0.001). EIDV was not significantly different between patients with and without LVH and controls. In conclusion, the presence of LVH was related to endothelial dysfunction, both in untreated and treated hypertensive patients, suggesting either a role for endothelial function in the development of LVH, or that a dysfunctional endothelium and LVH are coexisting markers of a more severe hypertensive disease.

Ambulatory blood pressure and endothelium-dependent vasodilation in hypertensive patients.

Endothelial function is important for local vascular regulation and an abnormal endothelium-dependent vasodilatation (EDV) has been observed in subjects with essential hypertension. As ambulatory blood pressure (ABP) is more closely related to target organ damage than office blood pressure, this study investigated also if 24-h ABP is more closely related to an impaired EDV than office blood pressure recordings. In a group of 25 untreated patients with essential hypertension and an age- and sex-matched control group (n = 21) endothelial function was evaluated by measurements of forearm blood flow (FBF) during local intra-arterial infusions of metacholine (evaluating EDV) and sodium nitroprusside (evaluating endothelium independent vasodilation, EIDV). FBF was measured with venous occlusion plethysmography. Both office mean artery pressure (MAP; r = -0.57, p < 0.001) and 24-h ABP (r = -0.40, p < 0.01) were related to the endothelial vasodilator function (EDV to EIDV ratio) in an inverse way, but ABP was not superior to office blood pressure recordings. Within the hypertensive group, pronounced white-coat effect (office minus daytime ABP) was associated with a reduced EDV (r = -0.41, p < 0.05). The degree of night-time decline in blood pressure (?dipping?) showed no correlation to EDV. In conclusion, the finding that ABP was no more closely related to the endothelial vasodilator function than office blood pressure recordings might be due to an increased mental alertness affecting EDV in some hypertensive subjects, as suggested by the finding of a reduced EDV in those with a pronounced white-coat effect.

Endothelium-dependent Vasodilatation in Treated and Untreated Hypertensive Subjects

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.