New insights into antiphospholipid-related endothelial dysfunction by assessment of vascular glycocalyx layer: results from a preliminary cross-sectional study.

INTRODUCTION: Antiphospholipid syndrome (APS) is associated with greater atherothrombotic risk and endothelial dysfunction, suggesting that endothelial glycocalyx is impaired in this disease. OBJECTIVES: The aim was to investigate the endothelial glycocalyx and the relationship between glycocalyx markers, endothelial dysfunction parameters and atherosclerotic markers in APS. METHODS: A total of 15 primary arterial APS patients and healthy controls were included in the study. Glycocalyx was assessed in both groups by sublingual sidestream dark field imaging and syndecan-1 plasma level. Endothelial function was evaluated by brachial artery flow-mediated dilatation (FMD) and early atherosclerosis by carotid intima media thickness (IMT). Thrombotic profile was also performed by measuring the plasma level of the tissue factor (TF). RESULTS: APS patients had significantly increased syndecan-1 plasma level 38.6 ± 5.0 pg/ml vs. 19.1 ± 3.5 pg/ml; p < 0.01 and a reduced glycocalyx thickness 0.26 ± 0.03 µm vs. 0.75 ± 0.07 µm; p < 0.01 compared with control. FMD was impaired in APS patients compared with control, 5.68% ± 0.42 vs. 8.29 ± 0.30, p < 0.01, respectively. IMT was significantly increased in APS patients compared with control, 0.52 ± 0.13 mm vs. 0.40 ± 0.06 mm, p < 0.01, respectively. Soluble TF, thiobarbituric acid-reactive substances levels were increased in the sera from APS patients compared with control. CONCLUSIONS: This preliminary study supports, for the first time, that in APS patients endothelial glycocalyx is impaired, which could lead to thrombosis, endothelial dysfunction and early atherosclerosis.

Immunosuppressant regimen based on sirolimus decreases aortic stiffness in renal transplant recipients in comparison to cyclosporine.

Whether or not a cyclosporine A (CsA)-free immunosuppressant regimen based on sirolimus (SRL) prevents aortic stiffening and improves central hemodynamics in renal recipients remains unknown. Forty-four patients (48 ± 2 years) enrolled in the CONCEPT trial were randomized at week 12 (W12) to continue CsA or switch to SRL, both associated with mycophenolate mofetil. Carotid systolic blood pressure (cSBP), pulse pressure (cPP), central pressure wave reflection (augmentation index, AIx) and carotid-to-femoral pulse-wave velocity (PWV: aortic stiffness) were blindly assessed at W12, W26 and W52 together with plasma endothelin-1 (ET-1), thiobarbituric acid-reactive substances (TBARS) and superoxide dismutase (SOD) and catalase erythrocyte activities. At W12, there was no difference between groups. At follow-up, PWV, cSBP, cPP and AIx were lower in the SRL group. The difference in PWV remained significant after adjustment for blood pressure and eGFR. In parallel, ET-1 decreased in the SRL group, while TBARS, SOD and catalase erythrocyte activities increased in both groups but to a lesser extent in the SRL group. Our results demonstrate that a CsA-free regimen based on SRL reduces aortic stiffness, plasma endothelin-1 and oxidative stress in renal recipients suggesting a protective effect on the arterial wall that may be translated into cardiovascular risk reduction.

[Role of vascular calcium-activated potassium channels in the regulation of human peripheral conduit artery diameter]. / Rô1e des canaux potassiques calcium-dépendants dans la régulation du diamètre basal des artères de conductance périphériques humaines.

The role of an endothelium-derived hyperpolarizing factor (EDHF), acting through the opening of vascular calcium-activated potassium (K(Ca)) channels, in the regulation of the basal diameter of human peripheral conduit arteries has never been investigated in vivo. We measured in 7 healthy subjects the effect of the local infusion of an inhibitor of K(Ca) channels, tetraethylammonium chloride (TEA, 9 micromol/min, 8 min), on radial artery diameter (echotracking) and flow (Doppler). Endothelium-independent dilatation was assessed before and after TEA using sodium nitroprusside (SNP: 5, 10 and 15 nmol/min, 3 min each). TEA induced a decrease in radial artery diameter (2.65 +/- 0.09 to 2.52 +/- 0.09 mm: p < 0.05) and flow (9.4 +/- 1.2 to 7.4 +/- 1.1 ml/min; p < 0.01) without modification in the radial artery dilatation in response to SNP (NS). The decrease in radial artery diameter was still significant even when the decrease in flow was taken as covariate into analysis (p < 0.05). These results demonstrate the role of vascular K(Ca) channels in the regulation of basal peripheral conduit artery diameter and arteriolar tone in human strongly suggesting the involvement of an EDHF a these two levels.

Role of basal and stimulated release of nitric oxide in the regulation of radial artery caliber in humans.

Although it is well established that nitric oxide contributes to the regulation of resistance arterial tone in humans, its role at the level of large arteries is less clear. Therefore, we assessed in healthy volunteers the effect of local administration of the inhibitor of nitric oxide synthesis NG-monomethyl-L-arginine (L-NMMA) on basal radial artery diameter (transcutaneous A-mode echotracking) and radial blood flow (Doppler) as well as on the radial response to acetylcholine and the nitric oxide donor sodium nitroprusside. A catheter was inserted into the brachial artery for measurement of arterial pressure and infusion of L-NMMA (2, 4 and 8 mumol/min for 5 minutes, n = 11), acetylcholine (3, 30, 300 and 900 nmol/min for 3 minutes, n = 8), and nitroprusside (2.5, 5, 10, and 20 nmol/min for 3 minutes, n = 6). None of the treatments affected arterial blood pressure or heart rate. L-NMMA dose-dependently decreased radial blood flow (from 31 +/- 6 to 17 +/- 3 10(-3) L/min after 8 mumol/min, P < .01) but did not affect radial artery diameter (from 2.93 +/- 0.11 to 2.90 +/- 0.14 mm). Acetylcholine dose-dependently increased radial blood flow (154 +/- 43% after 900 nmol/min) and radial artery diameter (16 +/- 4%), and both effects were markedly reduced after L-NMMA (increase in radial blood flow and radial artery diameter: 22 +/- 20% and 3 +/- 2%, respectively; both P < .01 versus controls). Nitroprusside also dose-dependently increased radial artery diameter (14 +/- 4% after 20 nmol/min) but only moderately affected radial blood flow (47 +/- 21%).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of nitric oxide in the regulation of the mechanical properties of peripheral conduit arteries in humans.

Whether nitric oxide (NO) contributes to the regulation of the mechanical properties of large arteries in humans is not known. We measured the effect of local administration of the inhibitor of NO synthesis N(G)-monomethyl-L-arginine (L-NMMA; 1 and 4 micromol x L[-1] x min[-1] for 5 minutes) and acetylcholine (3 and 30 nmol x L[-1] x min[-1] for 3 minutes) on radial artery diameter and wall thickness in 11 healthy volunteers using an echo-tracking system coupled to a measurement of radial blood flow (Doppler) and arterial pressure. At the highest dose, L-NMMA reduced radial blood flow but surprisingly decreased incremental elastic modulus (from 1.36+/-0.22 to 1.00+/-0.22 kPa x 10[3]; P<.05) and increased arterial compliance (from 3.20+/-0.46 to 4.07+/-0.45 m2 x kPa x 10(-8), P<.05), without affecting radial artery internal diameter, wall thickness or midwall stress, thus reflecting a decrease in vascular tone. Acetylcholine decreased incremental elastic modulus (from 1.27+/-0.08 to 0.88+/-0.07 kPa x 10[3]; P<.05) and increased arterial diameter, radial blood flow, and compliance (from 2.82+/-0.16 to 5.30+/-0.62m2 x kPa x 10[-8]; P<.05). These results demonstrate in vivo that NO is involved in the regulation of the mechanical properties of large arteries in humans. However, the effects of L-NMMA, ie, a decrease in arterial wall rigidity and an increase in arterial compliance, which occur in the absence of any changes in blood pressure or arterial geometry, suggest that inhibition of NO synthesis is associated in humans with a paradoxical isometric smooth muscle relaxation. This effect could be due to the development of compensatory vasodilating mechanisms after NO synthesis inhibition.

Fixed-dose combination of perindopril with indapamide in spontaneously hypertensive rats: haemodynamic, biological and structural effects.

OBJECTIVE: The present study was designed to test the effects of chronic combined treatment with low doses of an angiotensin converting enzyme inhibitor (perindopril) and of the diuretic indapamide in spontaneously hypertensive rats (SHR). METHODS: Adult SHR were treated with placebo or increasing doses of the combination of the drugs (0.3, 1 and 3 mg/kg per day; ratio of doses 0.32). In a separate set of experiments, the effects of the drugs combined (1 mg/kg per day) was compared with those induced by each drug alone. RESULTS: The drug combination dose-dependently decreased systolic blood pressure and its hypotensive effect was more marked than those induced by each treatment administered alone (untreated 208 +/- 5 mmHg, indapamide 185 +/- 5 mmHg, perindopril 150 +/- 3 and the combination 123 +/- 7 mmHg). A 12-week treatment with the drug combination (1 mg/kg per day) was not accompanied by any change in diuresis or urinary excretion of Na or K. The same treatment decreased cardiac hypertrophy and collagen. At the vascular level, the drug combination decreased aortic, carotid and femoral media cross-sectional areas, as well as aortic and carotid collagen density. This latter effect was accompanied by a significant increase in carotid artery compliance assessed in vivo at constant pressure. Finally, in isolated aortae, chronic combined drug treatment was associated with an increased basal release of nitric oxide and a decrease in the hypertension-induced endothelium-dependent contractions in response to acetylcholine. CONCLUSION: These experiments suggest that chronic combined treatment with low doses of an angiotensin converting enzyme inhibitor and a diuretic such as indapamide may be of value in the treatment of hypertension.

[Changes in the mechanical properties of the arterial wall evaluated in vivo in the spontaneously hypertensive rat]. / Modification des propriétés mécaniques de la paroi artérielle évaluées in vivo chez les rats spontanément hypertendus.

Recent experiments demonstrated increased isobaric arterial compliance and distensibility in hypertensive patients, which could be explained by a decrease in arterial wall stress, when assessed at constant pressure. We investigated the effect of hypertension on the mechanical properties of the carotid arterial wall, and especially wall stress, assessed in vivo in spontaneously hypertensive rats (SHR). Right carotid artery internal diameter (ID) and wall thickness (WT) were continuously monitored in 30 week old anesthetized SHR (n = 8) or their normotensive controls (WKY, n = 7), using a high resolution (1 micron) transcutaneous A-mode echo-tracking system (NIUS 2), coupled to a measurement of left carotid arterial pressure (micromanometer). Mean arterial pressure was 123 +/- 6 in WKY and 202 +/- 2 mmHg in SHR (p < 0.01). Mechanical parameters were calculated at mean pressure from ID and WT-pressure curves (*: p < 0.01 vs WKY). There was no difference between the groups for ID (WKY: 1.13 +/- 0.07; SHR: 1.20 +/- 0.06 mm, NS) and mid-wall stress (WKY: 10.5 +/- 1.2; SHR: 10.5 +/- 0.7 10(5) dynes/cm2, NS) while WT was increased in SHR (WKY: 105 +/- 8; SHR: 191 +/- 16 microns, p < 0.01). In SHR, incremental modulus (wall rigidity) was increased (WKY: 0.86 +/- 0.09; SHR: 1.96 +/- 0.25 10(7) dynes/cm2, p < 0.01) while distensibility (WKY: 1.77 +/- 0.16; SHR: 0.54 +/- 0.06 10(-3) mmHg-1, p < 0.01) and compliance (WKY: 1.84 +/- 0.30; SHR: 0.61 +/- 0.07 10(-3) mm2/mmHg, p < 0.01) were decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

[Role of endothelium-derived nitric oxide in sustained flow-dependent dilatation of human peripheral conduit arteries]. / Rôle du monoxyde d'azote dans la dilatation débit-dépendante des artères de conductance périphériques en réponse à une stimulation soutenue.

Endothelial dysfunction is involved in the pathogenesis of cardiovascular diseases and is generally associated to the decrease in arterial nitric oxide (NO) availability. In humans, endothelial function can be evaluated by the post-ischaemic flow-dependent dilatation (FDD) of peripheral conduit arteries which is mainly mediated by the NO release when short duration of reactive hyperaemia are used (3 to 5 min ischaemia). However, recent studies suggest that the role of NO in this response decreases as the duration of the hyperaemic stimulation increases. The aim of the present study was thus, to evaluate, in healthy subjects, the role of NO in the FDD of conduct arteries in response to a sustained stimulation. Radial artery diameter (echotracking) and flow (Doppler) were measured, 7 cm under the elbow line, at baseline and during post-ischaemic hyperaemia (10 min wrist cuff inflation) in 10 healthy subjects (age: 24 +/- 1 years) in control period and after acute blockade of the endothelial NO-synthase by local infusion of NG-monomethyl L-arginine (L-NMMA, brachial artery, 8 mumol/min, 7 min). Endothelium-independent dilatation was studied by mean of sodium nitroprusside infusion (SNP: 5, 10 and 20 nmol/min, 3 min each dose before and after L-NMMA). L-NMMA administration decreased radial artery blood flow at base (Control: 14 +/- 2 vs L-NMMA: 10 +/- 1 ml/min, P < 0.05) and increased radial artery vasodilatation in response to SNP (P < 0.05) thus, demonstrating NO-synthase inhibition. Therefore, after L-NMMA there was a small decrease in radial FDD (Control: base: 2.52 +/- 0.05 mm, FDD: 11.3 +/- 0.6% vs L-NMMA: base: 2.51 +/- 0.04 mm: FDD: 9.0 +/- 0.9%; p < 0.05) without change in hyperaemia. In conclusion, our results demonstrate, in contrast to those obtained after short duration of hyperaemia, that the relative implication of NO in the flow-dependent vasodilatation of peripheral conduit arteries in humans decreases in response to sustained stimulation and suggest, in these experimental conditions, an associated flow-dependent vasodilating mechanism that is unaffected by the NO-synthase inhibition.

[Mechanical adaptation of muscular arteries to acute increase of blood pressure in man. Contribution of the measurement of arterial wall thickness]. / Adaptation mécanique des artères musculaires à l'élévation aiguë de la pression artérielle chez l'homme. Apports de la mesure de l'épaisseur de la paroi artérielle.

Although it was usually admitted that hypertension is associated with a reduction in conduit artery compliance and distensibility, recent experiments using newly developed high precision echo-tracking devices allowing simultaneous, non-invasive measurements of blood pressure and arterial diameter have suggested that compliance and distensibility, when calculated at equal transmural pressure, could indeed be maintained, or even increased, in hypertensive subjects. Such a maintained arterial compliance could be explained best by a decrease in wall stress despite the increase in arterial blood pressure, through either an increase in wall thickness or a decrease in arterial wall elastic modulus. Thus, the goal of the present study was to assess the role of the changes in these determinants of vessel compliance in the arterial response to an acute increase in arterial pressure in 7 healthy volunteers. Arterial pressure (AP, Finapress) as well as right radial artery internal diameter and wall thickness (Echo-Tracking, NIUS 2, Asulab) were measured continuously before and after a 2 min cold pressor test (CPT). The following parameters were then calculated at fixed (105 mmHg) pressure from the pressure/diameter curve: compliance (mm2/mmHg) and distensibility (mmHg-1) mid-wall stress (dynes/cm2) and incremental elastic modulus (dynes/cm2). During CPT, mean AP increased (from 83 +/- 4 to 106 +/- 8 mmHg; p < 0.01), compliance distensibility; and mean internal diameter (mm) decreased, mean wall thickness (mm) increased, whereas wall stress and elastic modulus remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hand skin heating: a new method for the evaluation of conduit artery endothelial function in insulin-dependent diabetic patients]. / Le chauffa e cutané distal: une nouvelle méthode d'étude de la fonction endothéliale des artères de conductance périphériques chez le diabétique insulinodépendant.

The presence of an altered endothelium-mediated flow-dependent dilatation (FDD) of peripheral conduit arteries in insulin-dependent diabetic patients without microangiopathy is still controversial. We studied 10 normotensive and non atherosclerotic insulin-dependent diabetic patients (D group) without complication (neuropathy, microalbuminuria or neuropathy) and 10 control subjects (C group) matched for age, sex and BMI. Radial artery diameter (RAD, echotracking) and flow (RAF, Doppler) were measured at baseline and during FDD in response to distal hand skin heating (from 34 to 44 degrees C). a method developed to increase RAF by stable steps by decreasing gradually hand skin vascular resistance. Endothelium-independent dilatation was evaluated by administration of glyceryl trinitrate (GTN: 0.3 mg spray). At baseline, there was no difference between group for RAF (C: 18 +/- 5 vs D: 18 +/- 2 mL/min; NS) and RAD (C: 2.51 +/- 0.12 vs D: 2.54 +/- 0.07 mm; NS). Heating induced in the diabetic group a smaller increase in RAF (C: 473 +/- 126% vs D: 262 +/- 63%; p<0.05) and RAD (C: 22.6 +/- 2.6% vs D: 16.1 +/- 1.8%; p<0.01). This last result remains significant when the increase in RAF was included into the analysis of RAD variation during heating (p<0.05). GTN-induced dilatation was similar in the 2 groups. Our results obtained by use of the hand skin heating method demonstrate the presence of an abnormal arteriolar skin reactivity and an altered peripheral conduit artery endothelium-dependent dilatation in uncomplicated insulin-dependent diabetic patients. The early identification of these anomalies, with negative prognostic value, could contribute to the management of these patients.

[Role of nitric oxide in the regulation of the mechanical properties of peripheral muscular arteries in man]. / Rôle du monoxyde d'azote dans la régulation des propriétés mécaniques des artères musculaires périphériques chez l'homme.

Although several experiments have demonstrated the existence of a basal NO-dependent vasodilatory tone at the arteriolar level, the contribution of NO to the mechanical properties of large arteries has not been investigated in humans. To evaluate the effect of NO-synthase inhibition on these mechanical properties, radial artery internal diameter (d, mm) and wall thickness (h, mm) were measured continuously in 11 healthy volunteers (age: 24 +/- 1 years), using an A-mode echo-tracking system coupled to a Doppler device for the measurement of radial blood flow (RBF, ml/min). A catheter was inserted in the brachial artery for measurement of arterial pressure (AP, mmHg), and infusion of the inhibitor of NO synthesis NG-monomethyl L-arginine (L-NMMA: 4 mumol/min for 5 min, infusion rate 0.8 ml/min). Arterial compliance C, 10(-3) mm2/mmHg), distensibility (D, 10(-3)/mmHg), mid-wall stress (sigma, 10(5) dynes/mm2) and incremental modulus (Ei, 10(7) dynes/mm2) were calculated before and after L-NMMA. After L-NMMA, RBF decreased from 31 +/- 6 to 23 +/- 4 (p < 0.05), radial vascular resistance increased from 2.70 +/- 0.35 to 3.77 +/- 0.55 (p < 0.05), without changes in AP or heart rate. Table shows mechanical parameters, assessed at fixed AP (80 mmHg) (*: p < 0.05 vs baseline): [table: see text] Thus, the L-NMMA-induced decrease in radial arterial wall stiffness (Ei) without changes in arterial diameter or stress demonstrates that NO-synthase inhibition induces an isometric relaxation of vascular muscle cells, which explains the increase of arterial compliance at constant mid-wall stress. These results demonstrate that NO contributes to the regulation of peripheral muscular arterial mechanics in humans. At the level of large arteries, the isometric relaxation observed after NO-synthase inhibition is probably the consequence of compensatory vasodilator mechanisms.

[Role of nitric oxide in flow-dependent vasodilation of human peripheral arteries in vivo]. / Rôle du monoxyde d'azote dans la vasodilatation débit-dépendante d'une artère périphérique humaine in vivo.

Experiments performed in isolated arteries or in animals suggested that flow-dependent dilatation of conduit arteries is mediated through the release of endothelium-derived nitric oxide (NO). The present study was designed to assess whether NO also contributes to flow-dependent dilatation of conduit arteries in humans. Radial artery internal diameter was measured in 8 healthy volunteers (age 22 +/- 1 years), using a transcutaneous A-mode echo-tracking system, coupled to a Doppler device for the measurement of radial blood flow. A catheter was inserted in the brachial artery for measurement of arterial pressure and infusion of the L-arginine analogue NG-monomethyl L-arginine (L-NMMA (8 mumol/min for 7 min, infusion rate 0.8 ml/min). Flow-dependent dilatation was evaluated before and after L-NMMA as the response of the radial artery to an acute increase in flow (reactive hyperemia after a 3 min distal cuff occlusion). Release of the occlusion induced a significant increase in radial blood flow (from 27 +/- 4 to 82 +/- 13 ml/min; p < 0.01) followed by a delayed increase in radial diameter (flow-mediated dilatation; from 2.77 +/- 0.13 to 2.85 +/- 0.13 min; p < 0.01), without any change in heart rate or arterial pressure. L-NMMA induced a significant decrease in basal forearm blood flow (from 27 +/- 4 to 14 +/- 2 ml/min; p < 0.05), without affecting basal radial artery diameter, heart rate or arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

[Indications for angiographic study of renal arteries in elderly hypertensive subjects]. / Indications de l'exploration angiographique des artères rénales chez le sujet âgé hypertendu.

During a 30 months period, 70 patients (60-84 years old) underwent a renal artery angiographic investigation, either by combined intravenous angiography and pyelography, either by intravenous or intra-arterial digital angiography. Thirty-nine were males, 31 were females. All patients were hypertensive. Thirty-three had a normal renal function and 37 had a renal insufficiency arbitrarily definite as creatinine clearance lower than 60 ml/min (m = 33 +/- 15 ml/min). Eight aortic anevrysms were discovered. Thirteen patients (18.6%) had atherosclerotic renovascular disease. Criteria which led to undertake these investigations and results are listed in the following table. [table; see text] Transluminal percutaneous angioplasty and surgical treatment were performed 7 and 3 times respectively. In one case, nephrectomy was done. In all these patients but one, improvement of hypertension and/or renal function occurred. In patients with renal impairment, difference in size between the two kidneys detected by echography or plain abdominal X-rays were noted in 8 among the 9 patients with renovascular disease; six among them had proteinuria less than 0.5 g/day. In conclusion, in hypertensive patients older than 60, criteria for detection of renovascular disease are the same as in younger patients. When renal function is decreased, difference in size between the two kidneys requires an angiographic evaluation. Proteinuria does not exclude renovascular pathology.

[Drug-induced nephropathies]. / Les néphropathies médicamenteuses.

Drug-induced nephropathies are frequent. Glomeruli, tubes, interstitium and arterioles may be altered. In this paper, we have tried to know if clinical, biological or histological signs of drug-induced nephropathies are similar or different from those observed in idiopathic nephropathies. We demonstrate that drug-induced nephropathies do not present any particular clinical or biological signs. We find that minimal changes and membranous glomerulopathies are the main lesions observed. In contrast, glomerular proliferations are very rare. Drug-induced tubulopathies are characterized by tubular necrosis with variable extension. Interstitial lesions are absolutely identical to those observed in immunologically mediated nephropathies. Vascular lesions are very rare. It should be noticed that evolution of drug-induced nephropathies differs completely from idiopathic nephropathies. Indeed, renal lesions are usually regressive when the drug administration is stopped. In conclusion, it appears that drug-induced nephropathies mimic other forms of nephropathies. It is important to know that some drugs are excellent experimental models to reproduce some aspects of human renal pathologies.

Divergent effects of verapamil and amlodipine at rest and during exercise.

OBJECTIVE: To evaluate, in healthy volunteers, the effects of acute administration of two calcium antagonists with different pharmacological profiles, verapamil and amlodipine, on haemodynamics at rest and during exercise. SUBJECTS AND METHODS: Six healthy volunteers (aged 20-29 years) were randomly assigned to receive single oral doses of amlodipine (5 mg), slow-release verapamil (240 mg) or a placebo during a double-blind cross-over study. Systolic (SAP), diastolic and mean arterial pressures (measured using a cuff sphygmomanometer), heart rate (HR), cardiac index (CI, bioimpedance), rate-pressure product (SAP x HR), and noradrenaline and adrenaline plasma levels were measured at rest before drug administration, and at rest and during graded bicycle exercise (steps of 50, 100 and 150 W during 3, 3 and 4 min, respectively) started 3 h after drug administration. RESULTS: At rest arterial pressure, HR, rate-pressure product and catecholamine plasma levels did not change after verapamil or amlodipine administration, whereas CI significantly decreased after verapamil (from 3.9 +/- 0.4 to 3.3 +/- 0.4 l/min per m2) but not after amlodipine (3.9 +/- 0.3 and 4.1 +/- 0.5 l/m per m2) administration. During exercise the increases in SAP and HR were slightly but not significantly higher after amlodipine than after verapamil administration, rate-pressure product and CI were higher after amlodipine (22 +/- 1 x 10(3) mmHg x beats/min and 13 +/- 2 l/min per m2, respectively) than after verapamil (20 +/- 1 x 10(3) mmHg x beats/min and 10 +/- 2 l/min per m2, respectively) administration. Plasma levels of noradrenaline and adrenaline were similar at rest after each treatment and were slightly more increased after amlodipine administration during exercise. CONCLUSIONS: In contrast to amlodipine, verapamil induced a slight myocardial depressive effect at rest and did not potentiate the myocardial effects of the sympathetic stimulation induced by exercise. The myocardial action of verapamil is such as to induce some decrease in myocardial oxygen demand, both at rest and during exercise.

[Assessment of endothelial function in autoimmune diseases]. / Évaluation de la fonction endothéliale au cours des maladies auto-immunes.

Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to an increase in cardiovascular disease incidence. In addition to traditional cardiovascular risk factors, endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory and a proadhesive state, and prothrombic properties. Therefore, assessment of endothelial dysfunction targets this vascular phenotype using several biological markers as indicators of endothelial dysfunction. Measurements of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin), pro-thrombotic factors (thrombomodulin, von Willebrand factor, plasminogen activator inhibitor-1) and inflammatory cytokines are most often performed. Regarding the functional assessment of the endothelium, the flow-mediated dilatation of conduit arteries is a non-invasive method widely used in pathophysiological and interventional studies. In this review, we will briefly review the most relevant information upon endothelial dysfunction mechanisms and explorations. We will summarize the similarities and differences in the biological and functional assessments of the endothelium in different autoimmune diseases.

[Hypertension in the aged person. Numerous questions, few responses]. / Hypertension artérielle du sujet âgé. De nombreuses questions, quelques réponses.

Blood pressure levels increase with age. So, the prevalence of both isolated systolic (systolic pressure greater than 160 mmHg and diastolic less than 90 mmHg) and diastolic hypertension (diastolic pressure greater than 95 mmHg) in the elderly is high. Due to high variability of blood pressure and to overestimation of real blood pressure when arterial walls are sclerosed, the true prevalence of hypertension is probably overestimated. Nevertheless, like in younger persons, hypertension in elderly is a major risk factor of cardiovascular morbidity and mortality. Results of clinical trials designed in the last 30 years have clearly proved benefit of antihypertensive therapy. However, a lot of questions remain: Is treating hypertension justified in the very old? Has isolated systolic hypertension to be treated? Which antihypertensive drugs may be used? Is screening for atherosclerotic renovascular disease useful? Which investigations have to be performed for diagnosing atheromatous renal failure?

Role of arterial smooth muscle tone and geometry in the regulation of peripheral conduit artery mechanics by shear stress.

1. Although arterial blood flow is recognized as an important modulator of vascular tone and geometry, the effect of acute changes in shear-stress on conduit artery mechanics has not been fully investigated in humans because of technical limitations. 2. To assess, respectively, the effects of decreases and increases in flow and shear stress on radial artery tone and mechanics, arterial pressure (photoplethysmography), total blood viscosity, radial artery internal diameter, wall thickness (echotracking) and blood flow (Doppler) were measured in healthy volunteers (mean (+/-SEM) age 25 +/- 1 years) during a distal flow arrest (n=12) and hand skin heating (n=18). 3. Radial artery flow decreased from 31 +/- 4 to 7 +/- 1 10(-3) L/min during distal flow arrest (P < 0.001) and increased from 10 +/- 2 to 22 +/- 4 and 69 +/- 6 10(-3) L/min during heating (P < 0.001). At mean arterial pressure, these changes in flow were respectively associated with a parallel flow-dependent reduction and increase in diameter and midwall stress. There was no significant modification in mean elastic modulus. Compliance did not change when flow decreased and only increased at the highest level of flow. Finally, the cross-sectional compliance and incremental modulus were fitted as functions of midwall stress. The decrease in flow was associated with an upward shift of the modulus-midwall stress curve and a downward shift of the compliance-midwall stress curve. The increase in flow was associated with a downward shift of the modulus-midwall stress curve and an upward shift of the compliance-midwall stress curve at each level of wall shear stress. 4. By using two different procedures, we obtained similar results concerning the direct effects of increases and decreases in flow on stiffness of the arterial wall and on arterial compliance and demonstrated the presence of a flow-dependent regulation of arterial smooth muscle tone of peripheral conduit arteries in humans.

Influence of sympathetic tone on mechanical properties of muscular arteries in humans.

Although smooth muscle tone is a key determinant of mechanical properties of arteries in animal experiments, it has not yet been studied in humans because of technical limitations. To assess the influence of tone on arterial properties in humans and to emphasize the interest of calculation at specific stress, we used echo tracking and photoplethysmographic measurement of arterial pressure to study radial arterial mechanics during a cold pressor test (CPT) in 12 healthy volunteers (28 +/- 2 yr). During CPT, mean arterial pressure rose from 83 +/- 3 to 106 +/- 5 mmHg (P < 0.05), internal diameter decreased from 2.75 +/- 0.15 to 2.54 +/- 0.14 mm (P < 0.05), and wall thickness increased from 0.576 +/- 0.027 to 0.634 +/- 0.029 mm (P < 0.05). At a specific pressure (105 mmHg), midwall stress and incremental modulus decreased whereas arterial compliance increased. The incremental modulus of elasticity and compliance were fitted as functions of pressure and of midwall stress. CPT decreased the modulus about equally at all wall stresses measured. The modulus decreased and the compliance increased at every level of pressure measured. At all levels of midwall stress, the compliance was decreased. Thus acute sympathetic stimulation induced by CPT decreases the wall stiffness of human arteries in vivo. This may be explained by an unloading of stiffer wall components during active arterial constriction.