[The best of clinical pharmacology in 2004]. / L'essentiel de 2004 en pharmacologie clinique cardiovasculaire.

The year 2004 was not marked by major pharmacological advances, but by confirmation of previous "evidence". Several innovative drugs for stable angina (ranolazine, ivabradine), some interesting results in acute coronary syndrome (PROVE IT study), some classic concepts (cannabinoid receptors and their antagonists such as rimonabant) applied to novel indications (treatment of obesity), hopes for the "sartans" revived in the light of new evidence (VALUE study), advances in the management of diabetes and hypertension (ASCOT and CARDS studies), nebivolol which is not just a betablocker but also produces the NO radical (is this why it decreased the mortality of heart failure in the elderly in the SENIOR study?). In contrast, although Chronadalate did not live up to expectations for coronary insufficiency, the year was marked above all by the much heralded withdrawal of Vioxx for increasing cardiovascular risk. The old adage: primum non nocere springs to mind.

Design, baseline characteristics and carotid intima-media thickness reproducibility in the PARC study.

BACKGROUND: Intima-media thickness (IMT) is associated with an increased risk of cardiovascular and cerebral ischemic events, but its correlation with the absolute cardiovascular risk is not known in large populations. The Paroi Arterielle et Risque Cardiovasculaire (PARC) Study is an epidemiological study designed to correlate conventional assessment of cardiovascular risk with the mean IMT of the common carotid. METHODS: In the PARC study, 6,416 subjects were enrolled, including 80.7% subjects with cardiovascular risk factors and 19.3% without. A specific methodology was designed to harmonize the acquisition and processing of data at the 283 centers. Interreader agreement on image quality and IMT measurement of the common carotid artery (CCAIMT) was assessed from a random sample of 10% of the PARC study population. RESULTS: The intraclass correlation coefficient was 0.98 (95% CI 0.966-0.985), and the accuracy was high (standard deviation of the error measurement: 0.0185 mm). CONCLUSIONS: The reproducibility of the measurements assessed by means of the intraclass correlation coefficient and the accuracy of the CCAIMT measurement obtained in the PARC Study demonstrate the feasibility of large multicenter studies of IMT measurement.

[Differences between management guidelines and global health strategies for arterial hypertension with metabolic disorders in France in 1999. Ohara study]. / Différences entre recommandations de prise en charge et stratégie globale médicale dans l'hypertension artérielle avec désordres métaboliques en France en 1999. Etude Ohara.

Taking into account all the risk factors and blood pressure levels, as indicated by several American and European recommendations available since 1997, is a leading strategy to reduce mortality and morbidity of hypertensive patients. The aim of this study was to quantify how, in 1999. French practitioners applied recommendations on hypertension (HTN), diabetes and hypercholesterolemia in recently diagnosed hypertensive patients and to evaluate whether or not the recommended targets were met. 1639 French GPs and cardiologists included 5831 recently diagnosed (7.5 +/- 3.6 months) hypertensives (57 +/- 12 years of age, M/F = 55/45%). Initial BP was 173 +/- 15/99 +/- 9 mmHg. 56% had no concomitant disease, 36% had either diabetes, dyslipidemia or coronary heart disease, 8% had at least two concomitant diseases. At the time of the study corresponding to 6.3 +/- 3.8 months after initiation of diet and/or medical treatment, their BP was 148 +/- 17/86 +/- 11 mmHg (-25/-19 mmHg). At that time only 37% of patients with stage 2 HTN were encouraged to adopt lifestyle modifications without any medical treatment as recommended by the JNC VI. Among these hypertensives, measurement of plasma cholesterol was performed in only 61%, HDL-C/LDL-C in 26% and blood glucose in 51%. In the patients with dyslipidemia, LDL-C was measured in only 47%. In the 677 diabetic patients only 27% had a glycated hemoglobin measurement. The percentage of patients reaching target BP was 59% as regard DBP < 90 mmHg, 25% as regard SBP < 140 mmHg, and 23% reached both target values of BP. In addition, 30% of patients with dyslipidemia reached the target LDL-C as defined by French recommendations (ANAES 1996) and 30% of the diabetic patients reached the target value for glycemia recommended by ADA (1997). In 1999 in France, a minority of patients reaches the national or international recommended target values for blood pressure, glycemia and plasma LDL-cholesterol. In spite of that, French practitioners do not implement all the available diagnostic tools to improve the treatment of metabolic disorders in hypertensive patients. As a conclusion, to improve the prognosis of hypertensive patients, it is mandatory to raise the awareness of physicians about multiple risk factor management and help them implement the recommendations in their daily practice.

Decreased regional blood flow in patients with acromegaly.

BACKGROUND AND AIMS: One-third of acromegalic patients have hypertension. Acromegaly is also associated with intrinsic cardiac abnormalities known collectively as a hyperkinetic heart syndrome, which is characterized by an increased cardiac index and decreased systemic vascular resistance. As a result, blood flow should be increased in the regional vascular beds of acromegalic patients. The aim of the study was to measure, using direct methods, blood flow and vascular resistance at the level of the brachial artery in acromegalic patients with a confirmed hyperkinetic heart syndrome. PATIENTS AND CONTROLS: Twelve patients with active acromegaly (five females, seven males; mean (+/- SD) age, 43 +/- 10 years) were studied. Twelve age- and sex-matched normal subjects served as controls. METHODS: Right heart catheterization was used to measure the cardiac index and stroke volume and to calculate systemic vascular resistance in the acromegalic patients. Brachial haemodynamics were evaluated with a two-dimensional pulsed Doppler system (double transducer probe and range-gated time system of reception). The mean diameter of the brachial artery and mean blood velocity were measured and used to calculate mean blood flow. Vascular resistance was calculated in the brachial artery as the mean arterial pressure/blood flow ratio. RESULTS: Age, body weight, height, body surface area and heart rate were similar in the acromegalic patients and controls, while mean arterial pressure was higher in patients. The cardiac index and stroke volume were increased in the acromegalic patients, at 4.08 +/- 0.47 (mean +/- SD) l/min/m2 body surface area and 116.7 +/- 19.4 ml, respectively, while systemic vascular resistance was low (12.5 +/- 2.1 U). Brachial artery diameter was similar in the patients and controls. Brachial artery mean blood velocity (P < 0.01) and mean blood flow (P < 0.05) were lower in the patients than in the controls (3.35 +/- 1.26 vs. 5.12 +/- 1.74 cm/s, and 16.4 +/- 9.4 vs. 25.6 +/- 11.6 ml/min/m2, respectively). The higher mean arterial pressure and lower mean blood flow resulted in higher forearm vascular resistance in the patients than in the controls (132 +/- 61 vs. 83.8 +/- 47 mmHg/ml/s/m2, respectively, P < 0.01). CONCLUSION: While cardiac output is increased and systemic vascular resistance is decreased in active acromegaly, direct measurement of brachial artery haemodynamics showed lower regional blood flow and increased local resistance relative to healthy controls. These results suggest a heterogeneous distribution of cardiac output in acromegaly.

Hemodynamic Effects of Dilevalol Following Acute and Long-Term Administration in Normal and Hypertensive Subjects.

Forearm hemodynamics using pulsed Doppler flowmetry were studied in 12 healthy volunteers and 20 patients with mild to moderate hypertension before and after acute and long-term oral administration of the beta-blocking agent dilevalol. The study was performed using a double-blind design versus placebo. Both 200-mg and 400-mg dosages produced a significant acute blood pressure reduction in normotensive and hypertensive subjects. In hypertensive subjects, forearm vascular resistance was poorly modified, brachial artery diameter decreased significantly but only with long-term administration of the 400-mg dosage. A significant reduction in brachial artery tangential tension was consequently observed. The study provides evidence that Dilevalol produced a significant decrease in blood pressure in normotensive and hypertensive subjects in association with a decrease in brachial artery tangential tension.

[Vasoselective, substance-specific actions of isradipine on the great arteries of hypertensives in comparison to metoprolol]. / Vasoselektive, substanzspezifische Wirkungen von Isradipin auf die grossen Arterien bei Hypertonikern im Vergleich zu Metoprolol.

The effects of isradipine (Lomir, CAS 75695-93-1) and metoprolol (CAS 37350-58-6) on geometry and arterial compliance of the arteria brachialis of 14 patients each with essential hypertension were compared acutely and after three months of therapy by means of pulsed Doppler sonography and the determination of pulse wave velocity. A calculation model was used that allowed to determine the drug-specific effects on arterial diameter and compliance under isobaric conditions. Isradipine increased measured and isobaric diameter during short-term (p < 0.05) and long-term administration (p < 0.05) whereas metoprolol did not change it. Isradipine increased measured and isobaric compliance during short-term (p < 0.05) and long-term administration (p < 0.05). Metoprolol reduced measured compliance acutely (p < 0.01) and isobaric compliance acutely (p < 0.05) and long-term (p < 0.05). Drug-specific effects on compliance were different during short-term and long-term administration (p < 0.01); the diameter was influenced differently only during short-term administration (p < 0.05). These opposite drug effects on the A. brachialis are probably due to a vasoselective relaxation of smooth muscle in large arteries by isradipine and-in the case of metoprolol-arterial constriction. The increase of arterial compliance by isradipine reduces very effectively the load on the heart and could form the basis for the improvement in the prognosis of the hypertensive patient.

Intrinsic effect of antihypertensive treatment with isradipine and metoprolol on large artery geometric and elastic properties.

The effects of isradipine and metoprolol were studied on the brachial arteries of two groups of 14 patients with hypertension, 90 minutes after the first dose and after 3 months of treatment. Diameter (pulsed Doppler) and compliance (pulse-wave velocity) were measured and calculated in isobaric conditions by way of a model that allowed discrimination of the active intrinsic drug action. Isradipine increased measured and isobaric diameter during short-term (p < 0.05) and long-term administration (p < 0.05), whereas metoprolol did not change it. Active diameter effects were different between drugs during short-term administration (p < 0.05). Isaradipine increased measured and isobaric compliance during short-term (p < 0.05) and long-term administration (p < 0.05). Short-term administration of metoprolol decreased measured compliance (p < 0.01). Metoprolol decreased isobaric compliance during short-term (p < 0.01) and long-term (p < 0.05) administration. Active compliance effects were different between drugs during short- and long-term administration (p < 0.01). These arterial intrinsic drug effects, independent of the pressure-lowering influence, suggested different mechanisms, consisting of a large artery smooth muscle relaxation for isradipine and an isometric arterial constriction for metoprolol.

Non-beta-adrenergic-mediated peripheral circulatory hyperkinesia in hyperthyroidism.

Systolic time intervals and brachial circulation, evaluated by pulsed Doppler in terms of arterial diameter, blood velocity and flow, and vascular resistance, were studied in 12 hyperthyroid patients and in 12 normal controls. In patients, arterial circulation was studied before and during mechanical exclusion of the hand, and hemodynamic measurements were repeated after beta-blocker treatment and after obtainment of euthyroid state. Compared with controls, patients had higher heart rate (P < 0.001), lower systolic time intervals (P < 0.05, P < 0.01), and higher blood velocity (P < 0.05). Beta blockade decreased heart rate (P < 0.05, P < 0.001) but did not change systolic time intervals and arterial circulation. Euthyroid state decreased heart rate (P < 0.01), preejection period (P < 0.01), and blood velocity (P < 0.01) and flow (P < 0.05). The decreases in velocity and flow before hand exclusion when euthyroid state was obtained were correlated with hyperthyroid values of velocity and flow respectively (r = 0.85, r = 0.90, P < 0.01, P < 0.001). Vascular resistance during hand exclusion was correlated negatively with serum T3 level during hyperthyroid and euthyroid states. Thus, thyroid hormones but not beta-adrenoreceptors participate in the peripheral hyperkinesia of hyperthyroidism.

Diuretics and arteriolar resistance and arterial compliance in human hypertension.

Differences exist between short- and long-term haemodynamic effects of diuretics. In the short term, plasma volume depletion is accompanied by increased peripheral vascular resistance and decreased cardiac output. In the long term cardiac output returns toward normal, peripheral resistance falls to below pretreatment values and blood volume remains lower than before therapy. This long-term decrease in volume may contribute to the chronic antihypertensive effects of diuretics. Many studies have reported that arterial compliance is increased after antihypertensive drug administration. However, it is important to known whether such action is a primary pharmacological effect or mediated by the reduction in blood pressure. Two different methods using pulse wave velocity measurements have been applied to determine the pressure-dependence of compliance before and after thiazide administration. In the first method, blood pressure was controlled as a variable by changing transmural pressure of the forearm encased in a rigid plastic tube. In the other method arterial compliance in the brachial artery was evaluated using a simple non-linear arterial model. Both methods demonstrated that the decrease in blood pressure with thiazide therapy was associated with increased arterial compliance. However, by measuring arterial compliance at the same pressure, its isobaric values were found to be unchanged. The implication is that the increase in compliance of the peripheral artery observed with diuretics is due to the decline in blood pressure rather than to a change in the intrinsic properties of the arterial wall.

Comparative effects of diabetes mellitus and hypertension on physical properties of human large arteries.

OBJECTIVES: The effects of hypertension and diabetes on the physical properties of large arteries were compared in men. BACKGROUND: Although these two diseases are linked to vascular stiffening, no study has analyzed whether the arterial rigidity in diabetes is as substantial as in hypertension. METHODS: Noninvasive measurements of brachial artery mean pressure, diameter (pulsed Doppler study) and compliance (pulse wave velocity) were obtained in 29 men: 11 control subjects, 9 hypertensive nondiabetic patients and 9 diabetic normotensive patients. Individual diameter- and compliance-pressure curves extrapolated from the measured diameter and mean pressure point with a logarithmic elastic model permitted calculation of isobaric diameter and compliance at the same pressure in each subject. RESULTS: Compared with control subjects, hypertensive patients had a larger brachial artery measured diameter and isobaric diameter (p < 0.01) and lower measured and isobaric compliance (p < 0.001, p < 0.01). Compared with control subjects, diabetic patients had lower measured and isobaric compliance (p < 0.01). Comparison of diabetic and hypertensive patients showed that measured diameter and isobaric diameter were decreased in the former (p < 0.01). In the control and hypertensive groups, mean pressure correlated positively with measured diameter and isobaric diameter (p < 0.01) and negatively with measured and isobaric compliance (p < 0.001 and p < 0.01, respectively). In the control and diabetic groups, fasting glucose correlated negatively with measured and isobaric compliance (p < 0.01, p < 0.05). CONCLUSIONS: Intrinsic alterations of the large artery independent of a stretching pressure effect reduce arterial elasticity similarly in those with hypertension or diabetes. The loss of compliance is related to the chronic elevation of blood pressure in hypertension and to that of glycemia in diabetes and is associated with a relative large artery vasoconstriction in diabetic patients as compared with patients with hypertension.

Serum Lp(a) as a discriminant marker of early atherosclerotic plaque at three extracoronary sites in hypercholesterolemic men. The PCVMETRA Group.

To investigate the role of lipoprotein (a) (Lp[a]) as an atherogenic condition related to hypercholesterolemia, we studied the serum concentration of Lp(a) as measured by immunonephelometry in relation to the presence of asymptomatic echographic plaques in the peripheral arteries of 103 untreated hypercholesterolemic, normotensive, middle-aged men. Plaque was found at carotid, aortic, and femoral sites in 36%, 51%, and 53% of subjects, respectively. The Lp(a) level was higher in the group with carotid plaques than in the group without (0.29 +/- 0.20 versus 0.17 +/- 0.14 g/l, p < 0.01), not significantly higher in the group with aortics plaque than in the group without (0.24 +/- 0.19 versus 0.19 +/- 0.16 g/l), and not different between groups with and without femoral plaques (0.21 +/- 0.18 versus 0.22 +/- 0.17 g/l). A logistic regression analysis confirmed that Lp(a) was associated with carotid plaques (p = 0.004), independent of other risk factors. However, in patients with low density lipoprotein cholesterol values above the group median value (4.7 mmol/l), Lp(a) was associated not only with carotid plaques (p < 0.01) but also with aortic plaques (p < 0.05), as well as with the number of diseased sites (p = 0.02). In contrast, in patients with low density lipoprotein cholesterol levels below or equal to 4.7 mmol/l, Lp(a) only remained associated with carotid plaques (p < 0.05). Thus, in symptom-free, hypercholesterolemic men, early atherosclerosis was influenced by serum Lp(a), particularly in the carotid arteries, as well as by the presence of a higher level of low density lipoprotein cholesterol.

[Hypertension has no effect on coronary calcifications in asymptomatic patients with hypercholesterolemia]. / L'hypertension artérielle n'influence pas les calcifications coronaires chez l'homme hypercholestérolémique asymptomatique.

Since calcium in coronary artery walls is considered as an indicator for atherosclerosis, we used ultrafast computed tomography to quantify it non invasively in 111 hypercholesterolemic men. They were selected at worksite by a cholesterol screening program, had total cholesterol (TC) above 5.2 (6.88 +/- 0.82, SD) mmol/l, were aged from 30 to 63 (46 +/- 5 years), had never been treated with lipid lowering or antihypertensive drug, and had no clinical coronary heart disease. Body mass index, blood pressure, smoking and other serum lipids as HDL cholesterol, triglyceride (TG) were evaluated. Calcium score of proximal coronary arteries was calculated on 30 contiguous 3 mm slices from areas and peak density of calcium lesions. The mean score was 30 +/- 69 and ranged from 0 to 440. A zero score was found in 39 subjects who differed from the 72 others only by TG levels (1.44 +/- 0.60 vs 1.85 +/- 0.80; p < 0.05). A multiple regression analysis showed that elevated calcium score was associated independently to age (F = 6.6; p < 0.05) and TG (F = 6; p < 0.05) but not to blood. Thus 65% of these asymptomatic subjects had a non-zero calcium score in coronary arteries. Elevated calcium score was influenced independently by age and triglyceride level, but not by other risk factors, such as blood pressure. This potential adverse effect of moderate triglyceride elevation on large coronary arteries merits attention in the assessment of the risk of coronary heart disease.

Hypercholesterolaemia alters arterial and blood factors related to atherosclerosis in hypertension.

To evaluate the influence of hypercholesterolaemia on arterial and blood factors related to cardiovascular disease in hypertension, 20 normocholesterolaemic and 31 hypercholesterolaemic hypertensive patients underwent determinations of whole blood filterability (WBF), plasma fibrinogen concentration (PF) and aortic pulse wave velocity (PWV). Both of the groups had similar age, body mass index, cumulative smoking dose and blood pressure. Hypercholesterolaemics had lower WBF (P less than 0.02), higher PF (P less than 0.02) and higher PWV (P less than 0.01) than normocholesterolaemics. In the whole population WBF correlated with age (P less than 0.005), mean blood pressure (P less than 0.01), total cholesterol (P less than 0.05) and plasma fibrinogen (P less than 0.01). However, in a multivariate analysis where age and pressure were controlled as variables, only the association between WBF and PF remained significant (P less than 0.001). Thus, the higher fibrinogen affects whole blood filterability in hypercholesterolaemic hypertensive patients. In the whole population PWV correlated positively with HDL cholesterol (P less than 0.01) and age (P less than 0.001) and the association with HDL cholesterol remained significant in a multivariate analysis (P less than 0.001) where age was controlled. The effect of ageing on arterial rigidity seems to be similar in both hypertensive groups as deduced from the identical regression slopes relating pulse wave velocity to age. So in hypertension with high cholesterol, arterial rigidity was increased without changes in arterial stiffening with age.

Coronary calcification and its relation to extracoronary atherosclerosis in asymptomatic hypercholesterolemic men. The PCV METRA Group.

BACKGROUND: The prevalence of coronary calcifications and extracoronary plaques was studied in patients with asymptomatic hypercholesterolemia. METHODS AND RESULTS: Ultrafast computed tomography for coronary calcification (presence or absence: calcium score) and echographic assessment of carotid, aortic, and femoral plaques were performed in 111 hypercholesterolemic men: 65% had coronary calcification, 72% had extracoronary plaque. The two lesions were associated as: 1) compared with subjects without coronary calcification, those with calcification had a higher prevalence of aortic (p less than 0.05) and femoral (p less than 0.01) plaque and of two diseased sites (p less than 0.05); 2) the prevalence of coronary calcification was higher in the presence than in the absence of aortic (p less than 0.05) or femoral (p less than 0.01) plaque and higher in two (p less than 0.01) and three diseased (p less than 0.05) sites than in no diseased site; 3) the calcium score was higher in the presence than in the absence of carotid (p less than 0.05), aortic (p less than 0.05), or femoral (p less than 0.001) plaque, higher in two (p less than 0.001) and three diseased (p less than 0.05) sites than in no diseased sites, and higher in two (p less than 0.01) than in one diseased site; and 4) the calcium score correlated with femoral plaque (p less than 0.001). Overall, the presence of two or three diseased extracoronary sites versus no or one diseased site showed a power of 78% for predicting coronary calcification. Coronary calcium score correlated with age (p less than 0.01) and triglycerides (p less than 0.05). CONCLUSIONS: The close relation between coronary calcium and extracoronary plaques suggests that echography of extracoronary vessels could aid in the screening of coronary atherosclerosis in high-risk, asymptomatic individuals.

Active and passive effects of antihypertensive drugs on large artery diameter and elasticity in human essential hypertension.

The effects of antihypertensive drugs on the large arteries consist of two parts: the passive effect due to the change in pressure and the active effect, the drug action per se. This study proposes a method of dissociating the passive effect from the active effect. The diameter of the arterial artery was determined by the pulsed Doppler method and the pulse wave velocity of the brachioradial artery by mecanography. Arterial compliance was calculated by the Bramwell-Hill formula. Active and passive effects were determined by a logarithmic pressure-diameter model. This model was supported by in situ direct measurements of blood pressure and diameter in a segment of the femoral artery in dogs. Six drugs, cadralazine, ketanserin, medroxalol, nitrendipine, captopril, and isosorbide dinitrate, administered orally, were tested in 70 essential hypertensive patients. For all drugs, the pressure reduction induced a passive decrease in arterial diameter (p less than 0.02 to p less than 0.01). Cadralazine actively decreased arterial diameter (p less than 0.01), ketanserin had no active effect on diameter, and medroxalol, nitrendipine, captopril, and isosorbide dinitrate actively increased arterial diameter (p less than 0.05, p less than 0.01, p less than 0.01, and p less than 0.01, respectively). For all drugs, the pressure reduction also induced a passive increase in arterial compliance (p less than 0.05 to p less than 0.01). However, only nitrendipine, captopril, and isosorbide dinitrate actively increased arterial compliance (p less than 0.01, p less than 0.05, and p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of arterial compliance in the physiopharmacological approach to human hypertension.

Arterial compliance in humans is generally measured by modeling analysis of pulse tracing or of pulse wave propagation in the arterial tree. It is decreased in hypertension in part because elevation of blood pressure stiffens the arteries by stretching the rigid collagen fibres of their walls. Using a modeling evaluation of the compliance-pressure relationship in large arteries, it is possible to correct compliance from the mechanical effect (passive effect) due to pressure elevation. This makes it possible to show that, at the same pressure as in normal controls, hypertensive patients maintain decreased arterial compliance. This finding suggests that functional and/or structural changes other than pressure-mediated stretching of arteries (active effect) contribute toward reducing arterial compliance. Thus, the response of compliance to antihypertensive drugs must be studied by differentiating between passive and active effects. The diameter and compliance-pressure relationship in arteries allow differentiation of a passive arterial effect due to the pressure-lowering action of the drug, and an active pharmacological effect calculated at the same pressure before and after drug administration. Four drugs--ketanserin, urapidil, nitrendipine, and nicardipine (acute administration)--are given as examples. No active or passive compliance changes are observed with urapidil and ketanserin. In contrast, an active increase in compliance is observed in isobaric conditions with calcium antagonists, together with large-artery dilation due to a potent smooth muscle-relaxing effect. This active increase in compliance is potentiated by a passive increase due to the pressure-lowering effect that reduces the mechanical stretch exerted by blood pressure on arterial bioelastomers. Finally, an optimum increase in arterial compliance is achieved by drugs that vasodilate large arteries by smooth muscle relaxation and concomitantly decrease blood pressure. This may be of importance because low compliance has adverse effects on the cardiovascular system by contributing to the pathogenesis of systolic hypertension and left ventricular hypertrophy. Loss of arterial compliance may also be an early marker of atherosclerosis.

Physiopharmacological approach to mechanical factors of hypertension in the atherosclerotic process.

Hypertension may influence the atherosclerotic process of large arteries via pressure and shear forces. The pressure force dilates and stiffens arteries because of the non-linear elastic behaviour of arterial walls. This partly explains the increased diameter and decreased compliance of the brachial artery in hypertensive subjects compared with normotensive controls. However, pressure lowering by antihypertensive drugs does not always reverse large artery alterations indicating that other mechanisms are involved. Reversal of low compliance obtained with certain antihypertensive drugs is generally concomitant with large artery vasodilation, suggesting that smooth muscle relaxation plays a major role in the compliance response to drugs. Atherosclerosis associated with hypertension also causes additional loss of compliance and creates a vicious circle of sclerosis development by accelerating the biophysical fatigue of bioelastomers. Hypertension may contribute to atherogenesis by means of wall shear stress which is the frictional force exerted by the circulating blood column on the intima of arteries. Since it is likely that atherosis lesions may develop preferentially in low shear conditions, hypertension may promote the haemodynamic conditions of atherogenesis at the blood-wall interface. The response of wall shear to antihypertensive treatment is not unequivocal. For example, the beta-blocker, atenolol, does not change shear whereas carteolol increases shear rate and stress and these effects are closely related to change in platelet-free calcium concentration. This finding is consistent with the effect of shear forces on cell permeability to calcium demonstrated in vitro and points to the crucial role of wall shear as a biophysical signal capable of modifying the endothelial structure and function of arteries.

[Comparison of isobaric effects of hypertension and diabetes mellitus on geometric and elastic properties of human arteries]. / Comparaison des effets isobariques de l'hypertension artérielle et du diabète sur les propriétés géométriques et élastiques des artères humaines.

Hypertensive and diabetic mellitus diseases are known to increase stiffness of the arterial wall. However these alterations probably involve different mechanisms. To this end, we compared the effect of hypertension and diabetes on large artery caliber and elasticity at real pressure conditions and at the same level of pressure. Nine poorly controlled non insulino-dependent diabetic men without hypertension and 9 non-diabetic essential hypertensive men underwent measures of lumen diameter (pulsed Doppler) and segmental compliance (Bramwell and Hill formula; pulse wave velocity) at the brachial artery. Isobaric diameter and compliance were deduced from a non linear model, comparing diameter and pressure on one part, and compliance and pressure on the other. Pulse wave velocity was similarly increased in both diseases (11.5 +/- 1 vs 12.8 +/- 1 m/s; NS; respectively in diabetes and hypertension). Both measured and isobaric diameters were smaller in diabetic patients (4.05 +/- 0.2 vs 5.03 +/- 0.2 mm, p less than 0.1% for the measured diameters respectively in diabetes and hypertension and 4.06 +/- 0.2 vs 5.01 +/- 0.2 mm, p less than 1% for isobaric diameters). The measured and isobaric compliances were not significantly different (2.38 +/- 0.4 vs 2.08 +/- 0.2 cm/mmHg10(-4), NS, for the measured compliance respectively in diabetes and hypertension; 2.28 +/- 0.4 vs 2.4 +/- 0.2, NS for the isobaric compliance). After correction of the effect of mechanical arterial stretch induced by the different blood pressure level of the two groups, significant reduction of diameter in diabetic subjects persisted and isobaric and measured compliances remained unchanged between groups.