Brachial artery hyperemic blood flow velocities are related to carotid atherosclerosis

Objective: Cardiovascular (CV) risk relates to the blood flow velocity pattern in the brachial artery during hyperemia, especially to the hyperaemic systolic to diastolic mean blood flow velocity (SDFV) ratio. Here, we investigated the relations between SDFV in the brachial artery and different characteristics of carotid atherosclerosis. Material and methods: Data were collected from 1016 70‐year‐olds participating in the Prospective Investigation of Uppsala Seniors study. Doppler recordings of blood flow velocity during hyperemia were analysed in the brachial artery. In the carotid artery, intima‐media thickness (IMT) was recorded together with an assessment of echogenicity by the Grey scale median (GSM) method in both overt plaques and in the intima‐media complex (IM‐GSM). Results: The SDFV ratio was related to the number of carotid arteries affected by plaque (P = 0·018) and inversely to plaque echogenicity (P = 0·0003). The SDFV ratio was also related to IMT (P = 0·0022) and inversely to IM‐GSM (P = 0·0001). These relations were statistically significant also after adjusting for major CV risk factors, individually as well as summarised as the Framingham risk score. Conclusion: Our results indicate that the hyperemic systolic to diastolic blood flow velocity ratio in the brachial artery is related to atherosclerosis in the carotid artery.     

Evaluation of endothelium‐dependent vasodilation in the human peripheral circulation

Flow‐mediated vasodilation (FMD) in the brachial artery measured by ultrasound, and the increase in forearm blood flow (FBF) induced by local infusion of a muscarinic‐receptor agonist have both frequently been used to evaluate endothelium‐dependent vasodilation (EDV) in the human forearm. The present study intended to evaluate the relationship between these techniques and to investigate if vasodilation induced by the muscarinic receptor‐agonist methacholine (MCh) was owing to production of nitric oxide (NO). FMD during hyperaemia was assessed by ultrasound and FBF was measured by venous occlusion plethysmography during local infusion of MCh or L ‐arginine in the human forearm. Both these methods were applied in 26 individuals. In another 12 individuals forearm arterial and venous plasma concentrations of nitrate/nitrite (NOx) were measured together with FBF before and during local MCh infusion.While the change in brachial artery diameter induced by sublingually given nitroglycerine and the vasodilatory response to sodium nitroprusside (SNP) given locally in the forearm were significantly correlated (r=0·70, P<0·01), FMD showed no relationship with the vasodilation evoked by MCh (r=–0·03) or L ‐arginine (r=0·04). The five‐fold increase in FBF during MCh infusion was associated with a significant increase in venous plasma NOx concentrations (P<0·05) and a more than 11‐fold increase in forearm NOx‐release (P<0·01). Thus, a significant relationship between the two methods regarding the evaluation of endothelium‐independent vasodilation evoked by NO‐donors was found, but no relationship was found between the two methods regarding the evaluation of endothelium‐dependent vasodilation. Furthermore, vasodilation induced by MCh in the forearm seems to be induced by NO‐release.     

Arterial stiffness, but not endothelium-dependent vasodilation, is related to a low Ankle-Brachial index. The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS)

Background: Arterial compliance and endothelium‐dependent vasodilation are two characteristics of the vessel wall. In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study we studied the relationships between arterial compliance and endothelium‐dependent vasodilation versus the Ankle‐Brachial index (ABI), a clinically used index of peripheral artery disease. Methods: In the population‐based PIVUS study (all aged 70), arterial compliance was determined by ultrasound as the distensibility of the carotid artery and the stroke volume to pulse pressure (SV/PP) ratio by echocardiography, while endothelium‐dependent vasodilation was assessed by the invasive forearm technique with acetylcholine (EDV) and brachial artery ultrasound (FMD) in 519 subjects in whom the Ankle‐Brachial index was investigated. Results: After adjustments for gender and Framingham risk score, distensibility in the carotid artery and the SV/PP ratio were significantly reduced in subjects with a reduced ABI (<0·9) in both legs (n = 15, P = 0·0006 and P = 0·0003, respectively). Endothelium‐dependent vasodilation was not significantly related to a reduced ABI. Conclusion: A reduced arterial compliance, but not endothelium‐dependent vasodilation, was related to a low ABI in both legs after adjustment for major risk factors, suggesting that atherosclerosis in the leg arteries is associated with arterial compliance also in other parts of the vasculature.     

Comparison of ultrasound assessment of flow‐mediated dilatation in the radial and brachial artery with upper and forearm cuff positions

In the published literature relating to flow‐mediated dilatation (FMD), there are substantial differences between centres in terms of normal FMD amongst healthy subjects. This present study attempts to identify the effect of differing methodologies on FMD. High frequency ultrasound was used to measure blood flow and percentage brachial and radial artery dilatation after reactive hyperaemia induced by forearm or upper arm cuff occlusion in 24 healthy subjects, less than 40 years, without known cardiovascular risk factors. FMD of the brachial artery was significantly higher after upper arm occlusion, compared with forearm occlusion, 6·4 (3·3) and 3·9 (2·6)% (P<0·05), respectively. FMD of the radial artery was significantly higher after forearm occlusion, compared with upper arm occlusion, 10·0 (4·6) and 7·9 (3·5)% (P<0·05), respectively. The percentage blood flow increase in the brachial and radial arteries after forearm and upper arm occlusion were similar. After forearm and upper arm occlusion, the radial artery percentage dilatation was greater than the brachial artery. In conclusion dilatation of the brachial artery, after reactive hyperaemia induced by upper arm occlusion, was significantly more pronounced compared with dilatation of the brachial artery after forearm occlusion, despite a similar percentage blood flow increase. The local ischaemia of the brachial artery with a proximal occlusion may explain why the brachial artery dilated more after upper arm occlusion compared with after forearm occlusion. The study has also shown that FMD of the radial artery could be assessed by B‐mode ultrasound technique. FMD was greater using the radial artery compared with the brachial artery, suggesting that the radial artery may be a useful way to assess FMD in future clinical studies.     

Atherosclerosis measured by whole body magnetic resonance angiography and carotid artery ultrasound is related to arterial compliance,but not to endothelium‐dependent vasodilation – the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

Background: Arterial compliance and endothelium‐dependent vasodilation are two characteristics of the vessel wall. In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, we studied the relationships between arterial compliance and endothelium‐dependent vasodilation versus atherosclerosis as measured with two imaging modalities. Methods: In the population‐based PIVUS study (1016 subjects aged 70), arterial compliance was determined by ultrasound in the carotid artery and the stroke volume to pulse pressure ratio by echocardiography, while endothelium‐dependent vasodilation was assessed by the invasive forearm technique with acetylcholine and brachial artery ultrasound. Intima‐media thickness was evaluated by ultrasound in the carotid artery (n = 954). Stenosis in the carotid, aorta, renal, upper and lower leg arteries were determined by magnetic resonance angiography in a random subsample of 306 subjects. Results: After adjustments for gender, Framingham risk score, obesity, myocardial infarction and stroke, distensibility in the carotid artery and the stroke volume to pulse pressure ratio were both significantly related to a weighted index of stenosis in the five arterial territories evaluated by magnetic resonance angiography (p<0·02 for both). Distensibility in the carotid artery (P = 0·021), but not the stroke volume to pulse pressure ratio (P = 0·08), was also significantly related to intima‐media thickness. Conclusion: In the elderly population, atherosclerosis is mainly related to arterial compliance, but not to endothelium‐dependent vasodilation in peripheral conduit or resistance vessels.     

Arterial compliance and endothelium-dependent vasodilation are independently related to coronary risk in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

Background: Measurements of both arterial compliance and endothelium‐dependent vasodilation have previously been related to coronary risk factors, but not in the same study. In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, we studied the interplay between arterial compliance and endothelium‐dependent vasodilation on coronary risk. Methods: In the population‐based PIVUS study (1016 subjects aged 70 years), arterial compliance was determined by ultrasound in the carotid artery, by pulse wave analysis (augmentation index) and the stroke volume to pulse pressure ratio by echocardiography, while endothelium‐dependent vasodilation (EDV) was assessed by the invasive forearm technique with acetylcholine , brachial artery ultrasound [flow‐mediated dilatation (FMD)] and pulse wave analysis with terbutaline provocation [change in reflection index (RI)]. Results: Factor analysis disclosed three major factors. The first factor was reflecting the three arterial compliance methods, the second factor was reflecting EDV and the change in RI, while the third factor mainly was reflecting FMD. All these three factors were independently related to the Framingham risk score in multiple regression analysis (P<0·0001, P = 0·0002 and P = 0·0046, respectively). Conclusions: In conclusion, both arterial compliance and endothelium‐dependent vasodilation were independently related to the Framingham risk score, suggesting that it is worthwhile to evaluate the parallel use of these two vascular characteristics in a prospective fashion.     

Adding ischaemic hand exercise during occlusion of the brachial artery increases the flow-mediated vasodilation in ultrasound studies of endothelial function

A non-invasive method has been introduced to study endothelial function by evaluating flow-mediated, endothelium-dependent vasodilation of the brachial artery. One weakness of this method is that the post-occlusion vasodilation response is very small in subjects above the age of 60 years, which is a problem when quantifying endothelial dysfunction above this age. We have therefore evaluated whether a higher post-occlusion flow stimulus and a larger vasodilation response can be achieved by adding ischaemic hand exercise during the occlusion of the brachial artery. The subject population was men (n=12), aged 60 years, free from cardiovascular disease. B-mode ultrasound images for the measurement of lumen diameter of the brachial artery were recorded before and after reactive hyperaemia induced by occlusion of the artery. Blood flow velocity was recorded intermittently using a Doppler technique. Hyperaemia was induced in two different ways: first by occlusion only and then by adding ischaemic hand exercise during the occlusion. The results showed that flow velocity was higher and the duration of flow increase was longer after ischaemic hand exercise compared with occlusion only. Two minutes after cuff pressure release, the increase in blood flow velocity was significantly higher after ischaemic hand work compared with occlusion only (P<0·01). The corresponding maximal lumen diameters after cuff pressure release were 4·63 ± 0·35 and 4·45 ± 0·34 respectively (P<0·01). The flow-mediated vasodilation increased significantly from 2·24 ± 2·00% after occlusion only to 7·42 ± 3·32% after occlusion plus ischaemic hand exercise (P<0·01). In conclusion, this study showed that a maximal endothelial-dependent vasodilation was not achieved after occlusion only in these 60-year-old men. Adding ischaemic hand exercise may therefore be of value when quantifying endothelial dysfunction in this age group.     

Methodological aspects of the evaluation of endothelium-dependent vasodilatation in the human forearm

The present study, involving 56 healthy subjects from a health screening, was undertaken to address some methodological questions regarding the measurement of endothelial function using local intra-arterial infusions of metacholine (2 and 5 μg min^?1) to evaluate endothelium-dependent vasodilatation, and sodium nitroprusside (SNP, 5 and 10 μg min^?1) to evaluate endothelium-independent vasodilatation. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The ratio of FBF during the highest dose of metacholine to FBF during the highest dose of SNP was used as an index of endothelial function. In 10 young volunteers the procedure was repeated after 2 h and again after 3 weeks in order to study short-term and long-term reproducibility of the method. Neither the vasodilatatory response to metacholine (r = 0·006) nor that to SNP (r = 0·08) was related to resting FBF. Neither the circumference nor the length of the arm was related to endothelial function (r = 0·01?0·11), as evaluated by the FBF on metacholine to nitroprusside ratio (mean 1·3 ± 0·3 SD). The use of a wrist cuff to exclude hand circulation, or not, did not influence the evaluation of endothelial function significantly. Maximal FBF after 3 min of arterial occlusion of the forearm was significantly related to blood flow during both metacholine (r = 0·53, P < 0·01) and nitroprusside infusion (r = 0·36, P < 0·05), but not to the FBF on metacholine to nitroprusside ratio (r = 0·01). The short-term and long-term reproducibility of FBF during vasodilatation with metacholine and SNP was good (r = 0·89?0·97, P < 0·001), while the individual measurements for resting FBF were less reproducible when repeated after 3 weeks (r = 0·34). In conclusion, endothelial function was not related to resting FBF, nor to the arm circumference or length. No major difference was seen whether endothelial function was evaluated with or without exclusion of the hand circulation. Maximal FBF during reactive hyperaemia was not related to endothelial function.     

Endothelial function and hemodynamics in systemic sclerosis

Introduction: Systemic sclerosis (SSc) is characterized by the development of fibrosis of skin and internal organs that is associated with vascular damage. However, its related parameters have not been fully explored. The aim of this study was to investigate endothelial function in SSc and its relationship with systolic pulmonary artery pressure and systemic arterial compliance (SAC). Methods: We studied 14 SSc females (4 with diffuse and 10 with limited cutaneous form of the disease) and 14 healthy controls matched for age and for cardiovascular risk factors. Endothelium‐dependent dilation (i.e. flow‐mediated) and endothelium‐independent (i.e. nitroglycerin‐induced) dilation of the brachial artery were measured as the percentage of change from baseline (FMD and NMD, respectively). In patients with SSc, SAC, cardiac output (CO), systemic arterial resistance and pulmonary artery pressure were estimated using echocardiography Doppler. Results: Heart rate, brachial artery pressure and body mass index did not differ between patients with SSc and controls. Flow‐mediated vasodilation (FMD) and NMD were significantly decreased in patients with SSc (10·3 ± 8·6 versus 26·6 ± 7·4%, P<0·001; 24·2 ± 8·4 versus 33·3 ± 10·1%, P<0·001, respectively). Postischaemia reactive hyperaemia was lower in patients with SSc (275 ± 185 versus 618 ± 366%, P<0·001). FMD and nitrate‐mediated dilation (NMD) were associated with CO, but not with SAC; moreover, FMD correlated with pulmonary artery pressure and peripheral arterial resistance conversely to NMD. Conclusions: Endothelium function in SSc is impaired independently to SAC. Furthermore, the severity of both small artery and pulmonary artery involvement may impact on endothelium‐dependant function.     

Sustained hyperaemia stimulus is necessary to induce flow-mediated dilation of the human brachial artery

We studied the relative importance of the magnitude and duration of the shear stimulus to induce flow‐mediated dilation (FMD) in the brachial artery of 10 healthy men by ultrasound imaging. The shear stress stimulus was induced by different durations of reactive hyperaemia following 15‐min forearm occlusion. The control condition of continuous postocclusion hyperaemia was compared to 20, 40 and 60 s of reactive hyperaemia followed by reapplication of circulatory arrest for 2 min and a second cuff release. In response to the first cuff release, peak shear rate was not different between conditions; total shear during the first minute was reduced in the 40 s and further reduced in the 20 s conditions. FMD in control (10·0 ± 3·0%), 60 s (10·5 ± 3·2%) and 40 s (7·8 ± 3·6%) were greater than the 20‐s condition (2·9 ± 2·8%). At second cuff release, peak shear of the 20‐s condition was slightly reduced from the first release, but 40 and 60‐s conditions were progressively reduced. Total shear to peak dilation was reduced after the second cuff release for the 20 and 40‐s conditions and further after the 60‐s condition. FMD was maintained in the 20‐s condition (8·3 ± 3·7%) but reduced in the 40‐s (3·7 ± 1·7%) and 60‐s conditions (1·5 ± 2·6%). FMD was not related to peak shear rate after the first occlusion (r = 0·003) but was after the second cuff release (r = 0·32, P = 0·004). The FMD response was correlated with the total shear to time of peak diameter after the first (r = 0·35, P<0·001) and the second (r = 0·25, P = 0·009) cuff release.     

Endothelium-dependent vasodilation and structural and functional changes in the cardiovascular system are dependent on age in healthy subjects

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 μg min^–1), and endothelium-independent vasodilatation (EIDV) was assessed by nitroprusside infusion (SNP, 10 μg 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.     

The effect of enhanced external counterpulsation on C-reactive protein and flow-mediated dilation in porcine model of hypercholesterolaemia

Background: Lipid disorder causes vascular endothelial cell damage and contributes to the early development of dyslipidaemia‐induced atherosclerosis. In vivo and in vitro, it has been found that increasing shear stress can improve endothelial function. Clinically, enhanced external counterpulsation (EECP) plays important roles in the treatment of coronary artery disease by promoting arterial shear stress. The present study aims to evaluate the effect of EECP on vascular endothelial function in porcine hypercholesterolaemic model. Methods: Twenty‐six hypercholesterolaemic pigs were equally divided into EECP group (HC‐EECP group) and control group (HC group). Shear stress of a right forearm superficial artery was measured during EECP in comparison with the basal physiological status in the HC‐EECP group. Endothelial‐dependent flow‐mediated vasodilation (FMD) was applied to assess endothelial function. Serum high‐sensitivity C‐reactive protein (hs‐CRP) levels were measured at indicated time points. Results: Endothelial shear stress was increased significantly during EECP treatment (P<0·001). Compared to HC group, hs‐CRP decreased significantly by EECP at 18‐ and 36‐h, respectively (P<0·05). FMD was improved significantly by EECP compared to that of HC group at 18 h (11·09 ± 5·63%) and at 36 h (11·42 ± 2·75%) post‐EECP, P<0·05. Meanwhile, in animals of HC group, FMD was decreased from baseline 7·76 ± 3·70% to 6·75 ± 3·57% at 18 h and 5·07 ± 1·97% at 36 h, P<0·05. Conclusion: Long‐term EECP can improve endothelial function partially by an increased endothelial shear stress in hypercholesterolaemic porcine model. This implies that long‐term EECP can be used as a complementary therapeutic strategy to prevent atherosclerosis in hypercholesterolaemic patients.     

Postprandial impairment of resistance vessel function in insulin treated patients with diabetes mellitus type‐2

Reduced postischaemic reactive hyperaemia, is considered a marker of impaired resistance vessel function. Acute postprandial hyperlipidaemia has been shown to induce vascular dysfunction. In the present study, the impact of postprandial hyperglycaemia on resistance vessel reactivity was investigated in insulin treated type‐2 diabetic patients. The study was performed in 16 insulin treated type‐2 diabetics (eight male/eight female, age 47 ± 3 years, HbA1c 7·2 ± 0·2) and 16 controls. Reactive hyperaemia was measured in the forearm by venous occlusion plethysmography after 5 min of ischaemia in the fasting state and 90 min after a test meal. In diabetics, blood glucose increased from 8·7 ± 1·1 to 15·3 ± 1·0 mmol l^?1 (P<0·001) postprandially. This resulted in (i) a significant increase of resting blood flow (3·4 ± 0·3 to 4·8 ± 0·4 ml min^?1 100 ml^?1, P<0·01) and (ii) in a reduced peak reactive hyperaemia (52·3 ± 7·4 to 36·8 ± 4·3 ml min^?1 100 ml^?1, P<0·005). In controls, a similar effect of the meal on resting flow was observed but reactive hyperaemia was unaltered. In the absence of a test meal, basal flow as well as peak reactive hyperaemia remained unchanged in diabetic as well as in non‐diabetic subjects. Our data provide evidence that in the postprandial state resistance vessel reactivity becomes reduced in insulin treated type‐2 diabetic patients.     

Relationship of asymmetric dimethylarginine with flow-mediated dilatation in subjects with newly detected severe hypercholesterolemia

Background: Little is know about the relationship between asymmetric dimethylarginine (ADMA) and percent flow‐mediated dilatation (%FMD) in subjects with severe hypercholesterolemia (HH). Aim: The aim the present study was the evaluation of the relationship of ADMA to %FMD, as well as to lipid parameters and other markers of endothelial dysfunction in newly detected subjects with severe HH. Methods: One hundred and twenty asymptomatic patients with severe, newly detected HH and 100 controls were evaluated. The plasma level of ADMA was tested by ELISA and total homocysteine (tHcy) – through fluid chromatographic analysis. The %FMD was evaluated by the diameter of brachial artery with 7·5 MHz transducer of HP SONOS 5500. Results: Significant difference was found between patients and controls, (P<0·05) regarding lipid total cholesterol, triglycerides, high‐density lipoprotein, low‐dencity lipoprotein, atherogenic indices) and non‐lipid markers (ADMA, sICAM‐1, sVCAM‐1), as well as the endothelium dependent %FMD in contrast to flow independent vasodilation. (P>0·05) No significant difference was found between the groups with respect to tHcy, P‐selectine and E‐selectine. (P>0·05) A strong negative correlation was found between %FMD and ADMA. (r_xy = ?0·895; P<0·001), Apolipoprotein‐B (r_xy = ?0·687; P<0·0001, tHcy (r_xy = ?0·560; P<0·001) and Apolipoprotein index –B/A1 (r_xy = ?0·518; P<0·001). The subsequent linear and multiple regression analysis selected ADMA as the most significant factor in relation to %FMD. Conclusion: It is concluded that ADMA is the basic modulator of %FMD among all tested atherogenic risk biomarkers in in newly detected subjects with severe HH.     

Evaluation of gender differences in endothelium-independent dilation using peripheral arterial tonometry

Background: A change in peripheral arterial tonometry (PAT) in response to reactive hyperaemia is often used to provide a non‐invasive measure of endothelium‐dependent dilation (EDD). Reactive hyperaemia does not allow one to quantify endothelium‐independent dilation (EID), which is part of overall vascular function. Although most research examining vascular function and cardiovascular disease has focused on EDD, there is evidence that cardiovascular risk factors may impair EID. Purpose: To examine the microvascular vasodilation response to nitroglycerin (NTG) in healthy adults using PAT. Methods: Microvascular responses to reactive hyperaemia and NTG were evaluated in 86 (41 female and 45 male) healthy subjects (age 37 ± 5 years). Beat‐to‐beat plethysmographic measurements of finger arterial pulse waves were recorded for 5 min following reactive hyperaemia. After a 10‐min rest period, sublingual NTG (0·4 mg) was administered and PAT signal changes were measured for 10 min. Peak reactive hyperaemic index (RHI) and peak NTG‐mediated index (NMI) were determined in all subjects. Results: There were no significant gender differences in peak RHI (females: 2·07 ± 0·56 versus males: 1·91 ± 0·58, P = 0·20). Mean peak NMI for all subjects was 2·78 (±1·49). Peak NMI was significantly greater in females than in males (3·11 ± 1·59 versus 2·50 ± 1·34, P = 0·05). Time to peak NMI was not significantly different between genders (7 min, 28 s [±1 min, 47 s], versus 7 min, 14 s [±1 min, 49 s], P = 0·58). Conclusion: In this population of healthy adults, peak NMI was significantly greater in females than in males. These findings suggest that gender differences exist in the microvascular vasodilation responses to NTG using PAT.     

Effect of long-term beta-adrenergic-blockade on calf blood flow in hypertensive patients

Summary. The effect of a four-week treatment with propranolol and metoprolol on blood pressure and regional haemodynamics of the lower extremity at rest, after exercise and during reactive hyperaemia was studied in 34 patients with essential hypertension, but without peripheral arterial disease, in a randomized placebo-controlled trial. No significant difference in side-effects recorded during the trial was observed between these two drugs. Treatment with beta-adrenergic blocking drugs reduced systemic blood pressure. Calf blood flow during vasodilatation was also decreased. The most marked changes were observed during reactive hyperaemia; mean calf blood flow was reduced from about 250 ml/min/litre of tissue to 200 ml/min/litre of tissue (P<0·01) by propranolol and to 214 ml/min/litre of tissue (P<0·01) by metoprolol. Both drugs caused a significant increase in peripheral resistance above the initial level during reactive hyperaemia (P <0·05). No significant difference in peripheral resistance was observed, however, when the active drugs were compared with the placebo. There was no difference between propranolol and metoprolol in any of the parameters. Thus, the flow reduction can mainly be attributed to the diminished perfusion pressure due to the decreased cardiac output caused by beta-blockade of the heart.     

Determinants of post-ischaemic reactive hyperaemia in patients with diabetes mellitus type II

Dysfunction of resistance arteries is thought to be an early reversible stage in the development of atherosclerosis. Dynamics of post-ischaemic reactive hyperaemia are believed to constitute a useful tool for monitoring resistance vessel function. Patient characteristics influencing reactive hyperaemia, however, need to be defined more precisely. Since reactive hyperaemia is a dynamic process, yielding submaximal peak values after 5 min of ischaemia, this period was chosen to investigate the determinants of reactive hyperaemia in 100 type II diabetic patients as well as in 61 control subjects. Reactive hyperaemia was measured by venous-occlusion plethysmography; clinical and laboratory data were acquired by routine methods. Statistical comparison was performed with SYSTAT 5·0 for Apple Macintosh. Overall, no significant differences between diabetic patients and controls were observed by group comparison. In control subjects, only gender showed an influence on peak reactive hyperaemia (females 40·5 ± 15·3; males 51·8 ± 17·7 ml min^–1 100 ml^–1, P<0·01). In diabetic patients, in addition to gender, actual blood glucose (r=0·377, P<0·05) and meal intake (non-fasting 42·8 ± 19·2; fasting 51·2 ± 19·5 ml min^–1 100 ml^–1, P<0·05) were found to influence reactive hyperaemia. Further investigation revealed a loss of the correlation between peak reactive hyperaemia and actual blood glucose observed in the fasting state (P<0·001) in non-fasting diabetic patients, indicating an influence of meal intake on resistance vessel reactivity. Our results suggest that, in diabetic subjects, in addition to gender actual blood glucose and the postprandial situation impacts on peak reactive hyperaemia.     

应用彩色多普勒超声评价肱动脉血管内皮功能的研究

目的　探讨彩色多普勒超声(CDFI)评价肱动脉血管内皮功能的临床应用及其意义。方法　对30例原发性高胆固醇血症(PHC)患者给予辛伐他汀(SVT)治疗8周,用CDFI测定治疗前后反应性充血时和含服硝酸甘油后肱动脉内径的变化。结果　PHC患者SVT治疗前反应性充血时肱动脉内径的扩张程度为338%±548%,与正常对照组(1758%±64%)相比在统计学上有显著性差异(P<0001)。SVT治疗8周后反应性充血时肱动脉内径的扩张程度为1468%±505%,与治疗前相比明显改善(P<0001)。结论　应用CDFI可以准确、简便、有效地评价肱动脉血管内皮功能,对早期发现及评估动脉粥样硬化的发生等具有一定的临床价值。     

Effects of dipyridamole and theophylline on reactive hyperaemia in subcutaneous adipose tissue in humans

Summary. The importance of adenosine for reactive hyperaemia in subcutaneous adipose tissue was studied in healthy volunteers, using the adenosine uptake inhibitor dipyridamole (bolus 0·1 mg/kg i.v. followed by infusion of 0·7 μg/kg/min) and the adenosine receptor antagonist theophylline (4 or 6 mg/kg i.v.). Basal blood flow, total blood flow and hyperaemia (total minus basal flow) after a 20-min arterial occlusion were measured in the distal femoral region by the ¹³³Xe washout technique with and without drug treatment. Basal blood flow (mean±SEM) was 2·4 ± 0·3 ml/min/100 g, while total post-occlusive flow and total reactive hyperaemia were 97·3 ±8·4 and 61·8 ± 6·5 ml/100 g, respectively, without drug treatment. Basal blood flow was unaffected by dipyridamole but the total flow and hyperaemia were enhanced by 49 ± 24 and 60 ± 31%, respectively (P<·005 for both). This enhancement was due to increases in both amplitude and duration of the hyperaemia. Neither basal blood flow, total post-occlusive flow nor hyperaemia were significantly altered by theophylline. The amplitude of the enhanced hyperaemia during dipyridamole was not significantly counteracted by simultaneous theophylline treatment (6 mg/kg) but the duration of hyperaemia was reduced from 13 ± 1 to 8 ± 1 min (P<0·01). The results suggest that endogenous adenosine does not regulate basal blood flow or reactive hyperaemia of limited duration in human adipose tissue. However, reactive hyperaemia may be enhanced by pharmacological elevation of endogenous adenosine levels.     

Polymorphisms in the renin–angiotensin system and endothelium‐dependent vasodilation in normotensive subjects

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.