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Biomedical subjects

A Benetos

Publications and source records attributed to A Benetos.

At least 109 records · Page 6Linked to original sources
PubMed1992

Dose optimization study of arterial changes associated with angiotensin converting enzyme inhibition in hypertension.

BACKGROUND: In treating hypertension the optimal dose of angiotensin converting enzyme (ACE) inhibitor is derived from dose-response curves that relate the quantity of drug taken to the resulting fall in blood pressure; the blood pressure fall reflects a decrease in vascular resistance and hence, a degree of arteriolar vasodilation. However, ACE inhibition dilates not only the small arteries but also the larger calibre arteries, which increases compliance. Given the differences in structure and function of large and small arteries, the optimal drug dose for a given vessel may differ according to the size and structure of the vessel. DOSE-RESPONSE EFFECTS IN CLINICAL STUDIES: Clinical studies indicate that in the brachial artery territory, larger doses are required to obtain arterial dilation than to produce a decrease in vascular resistance. In the aorta, an improvement in arterial compliance and distensibility is governed both by the fall in blood pressure and the drug dose. Finally, for the femoral artery, the degree of arterial dilation is influenced markedly only by the drug dose. APPLICATION TO TREATMENT: An understanding of the drug dose required to produce a given change in the hypertensive arterial system may have important implications for the control of blood pressure. For a given mean arterial pressure, systolic blood pressure is lower and diastolic blood pressure higher when aortic compliance is increased, a haemodynamic change commonly seen following ACE inhibition. Recent double-blind studies have shown that ACE inhibitors produced a more pronounced decrease in systolic than diastolic blood pressure. CONCLUSION: These findings indicate that the optimum doses required to improve the arterial wall in large arteries must be evaluated by long-term antihypertensive therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Physiological and pharmacological changes in the carotid artery pressure-volume curve in situ in rats.

AIM: To measure the mechanical properties of the rat carotid artery as affected by physiological and pharmacological changes. METHODS: We used an in situ measurement method that did not affect the anatomy, vascularization or innervation of the carotid artery, in normotensive and in spontaneously hypertensive rats (SHR), to evaluate the effects of ageing, hypertension and acute or chronic drug-induced vasorelaxation. RESULTS: The compliance-pressure curve was characterized, under baseline conditions, by two phases, an ascending component in the lower pressure ranges and a descending component in the higher pressure ranges. In younger or older normotensive rats the maximum value of carotid compliance was observed for values of transmural pressure that approximated those of the operating mean blood pressure. For any given value of transmural pressure, carotid compliance was lower in the hypertensive rats, whether younger (3 months) or older (18 months), than in normotensive rats. This finding was particularly striking for transmural pressures below 125 mmHg, and held true even after the administration of potassium cyanide. Consequently, the reduced compliance in the hypertensive rats was attributed predominantly to structural changes in the arterial wall. Moreover, in the hypertensive rats there was a dissociation between the operating arterial blood pressure level and the maximum value of carotid arterial compliance. Thus in young SHR, whereas the operating systemic blood pressure was shifted toward higher values (> 175 mmHg), the maximum value of carotid compliance was observed for pressure levels close to 125 mmHg. This dissociation was more pronounced in older SHR (mean blood pressure 200 mmHg; maximum compliance 75 mmHg). CONCLUSIONS: The acute administration of vasodilators or of potassium cyanide induces relaxation of vascular smooth muscle and increases compliance for distension pressures of up to 125 mmHg. Since the drugs had no effects on arterial compliance at higher pressure levels, we conclude that in SHR acute vasorelaxation can increase operating compliance only if blood pressure is reduced. In contrast, chronic treatment with vasodilating agents is able to increase compliance even for higher blood pressure levels. Therefore, we suggest that chronic treatment can improve the elastic properties of the arterial wall through changes in the arterial wall structure.

Aging↗
PubMed1992

Sodium, large arteries and diuretic compounds in hypertension.

BACKGROUND: Clinical and experimental data have shown that different antihypertensive drugs do not cause similar changes in arterial compliance for an equipotent blood pressure reduction. There are no clear data on the effects of sodium and diuretics on the visco-elastic properties of the hypertensive arterial wall. DATA ANALYSIS: Cross-sectional epidemiological studies suggest that for given values of age and blood pressure, pulse wave velocity is lower in the presence than in the absence of a low sodium intake. Longitudinal studies indicate that in hypertensive subjects, a low sodium intake is associated with a larger brachial artery diameter than that seen with a high sodium intake. In hypertension in the elderly and in severe hypertension with end-stage renal disease, a sodium overload reduces arterial compliance and distensibility independently of blood pressure changes. In animal studies, the diuretic compounds cycletanine and indapamide increase systemic and carotid compliance independently of blood pressure changes. In contrast, in a crossover study in hypertensive subjects, the diuretic agent hydrochlorothiazide did not change arterial compliance and pulse wave velocity while the calcium entry-blocker felodipine did improve these hemodynamic parameters. CONCLUSION: The studies reviewed indicate that sodium may act on the arterial wall independently of blood pressure changes. the contribution made by counter-regulatory mechanisms, which may be related to the renin-angiotensin and the sympathetic nervous systems, might explain the differences between the clinical and the experimental changes observed with diuretic compounds.

Animals↗
PubMed1992

Opposing effects of ageing on distal and proximal large arteries in hypertensives.

AIM: Hypertension has been reported to accelerate the alterations in large arteries induced by ageing. Distal large arteries have been poorly investigated in contrast to proximal large arteries. The objectives of this cross-sectional study were (1) to compare the storage capacity of different arterial sites in normotensive subjects or hypertensive patients; and (2) to compare the different arterial sites with respect to the effects of ageing on storage capacity, in normotensives and in hypertensives. METHODS: Two recently developed ultrasonic echo-tracking devices, offering a high resolution for the assessment of internal arterial diameter and its systolo-diastolic variations, were used to measure end-diastolic diameter, absolute (change at end-systole minus change at end-diastole) and relative (absolute change divided by change at end-diastole) changes in diameter with stroke and the absolute change in cross-sectional area (3.14 x the end-diastolic diameter x half the absolute stroke change in diameter) at the site of the common carotid artery, the abdominal aorta, the common femoral artery, the brachial artery and the radial artery in 50 untreated essential hypertensive patients and 32 normotensive subjects. RESULTS: In both groups, the end-diastolic diameter increased with age for the common carotid artery and the abdominal aorta but not for the common femoral, brachial or radial arteries. In the normotensives, the relative stroke change in diameter was negatively correlated with age for the common carotid artery (P < 0.001) and the abdominal aorta (P < 0.001), and not correlated for the common femoral, brachial and radial arteries. In hypertensives, the relative stroke change in diameter was negatively correlated with age for the common carotid artery (P < 0.05) and the abdominal aorta (P < 0.05), positively correlated with age for the common femoral (P < 0.05) and the radial arteries (P < 0.05) and not correlated for the brachial artery. Similar results were observed for the relationships between the absolute change in cross-sectional area and age. CONCLUSIONS: In hypertensives, enlargement of the proximal large arteries offsets the decrease in the relative stroke change in diameter and maintains an adequate storage capacity. It thus appears that ageing exerts opposing effects on central elastic large arteries and distal muscular medium-sized arteries.

Adult↗
PubMed1992

Converting enzyme inhibition: dissociation between antihypertensive and arterial effects.

In this study the dose-response curves reflecting the arterial and the antihypertensive effects of converting enzyme inhibition were analysed. The BP measurement (using a random zero sphygmomanometer) and its decrease following converting enzyme inhibition were used as a marker of the arteriolar effect of the drug. The effect on conduit arteries was evaluated through determination of carotid-femoral pulse wave velocity used as an index of arterial distensibility. We compared the dose-response curves of these two parameters in a double-blind study carried out in 24 patients with essential hypertension, who were randomised between placebo and 2, 4 and 8 mg of the converting enzyme inhibitor trandolapril given for 8 days. The antihypertensive effect was observed from 2 mg, at which dose the plateau of BP reduction was already achieved. No significant correlation was found between dose and BP reduction (r = -0.34), whereas the dose was significantly related to the change in pulse wave velocity (r = -0.56, P < 0.01). No significant correlation was found between changes in BP and change of pulse wave velocity. The study provides evidence that the effect on the conduit artery was obtained for higher doses than the BP effect in patients treated for hypertension by the converting enzyme inhibitor trandolapril.

Adult↗
PubMed1992

[Non-invasive methods in the study of the elastic properties of the thoracic aorta. Effect of isosorbide dinitrate].

The role of the great arteries is to distribute and stock blood. Pulsatile discontinuous flow is transformed to a continuous flow system. The elastic properties of the aorta play a major role in these functions. It is generally agreed that changes in these elastic properties may lead to the development of left ventricular hypertrophy. The evaluation of the aorta has, until recently, depended on invasive hemodynamic and angiographic techniques. In addition, the measurement of pulse wave velocity, though useful, is a global and only an approximate method. Transoesophageal echocardiography (TEE) enables accurate measurement of the aortic diameter and its systolo-diastolic variations. The accuracy of these measurements has been validated in vitro and the reproducibility is much better than with previously used techniques. Previous studies have shown an improvement of the elastic properties of the great arteries with nitrate derivatives. In recent studies using TEE, isosorbide dinitrate caused dilatation of the descending thoracic aorta and thereby improved its elastic properties. The development of tonometry techniques in our department has resulted in the finding of excellent correlations between carotid and aortic pulse pressures measured non-invasively. The association of TEE and tonometry thereby provides a direct approach to the evaluation of aortic compliance. It has then become possible to study the effects of nitrate derivatives on the aortic compliance of elderly patients in whom it is the most reduced.

Aorta, Thoracic↗
PubMed1991

Response to the cold pressor test in normotensive and hypertensive patients.

The response to the cold pressor test (CPT) was studied in 49 normotensive (NT) and 73 patients with essential sustained hypertension (HT). Patients were classified as responders when they increased their systolic pressure (SBP) by at least 16 mm Hg or their diastolic blood pressure (DBP) by at least 12 mm Hg. Forty-seven out of seventy-three (64%) increased their mean blood pressure (MBP) by 18.6 +/- 1.4 mm Hg (mean +/- SEM) in response to CPT. In NT subjects 23 out of 49 (47%) were responders (MBP = 16.3 +/- 1.3 mm Hg). In NT, but not in HT, patients, a negative relationship was observed between MBP changes during CPT and age (P less than .001) or basal DBP (P less than .01). There was no relationship between blood pressure response and the presence of a family history of hypertension. A positive correlation was found in HT patients between basal levels of active renin (AR) in the upright position and MBP changes during CPT (P less than .001). Mean plasma AR was 24.2 +/- 3.5 pg/mL in nonresponders v 37.5 +/- 2.9 pg/mL in responders (P less than .001). In HT, but not in NT, patients, blood pressure changes were associated with a simultaneous increase in HR (P less than .01 between delta MBP and delta HR). These results suggest that blood pressure elevation during CPT is a very common reaction in young normotensive subjects especially in those that have the lowest mean blood pressure. Therefore it is unlikely that CPT may be used as a predictor test of future hypertension in this population.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1991

Effects of ramipril on arterial hemodynamics.

The acute and chronic arterial effects of the angiotensin-converting enzyme (ACE) inhibitor ramipril were studied in hypertensive patients. Hemodynamic and biological parameters were measured 3 h after the first dose of 5 mg of ramipril, and then again after 4 weeks of treatment, 3 and 24 h after drug administration. Brachial and carotid artery hemodynamics were evaluated using a two-dimensional pulsed Doppler system. Arterial distensibility was studied noninvasively in three arterial segments (carotidofemoral, brachioradial, and femorotibial) by evaluating the pulse wave velocity. Ramipril lowered the blood pressure significantly after acute and chronic administration. Chronic treatment with ramipril was followed by a long-lasting increase in brachial artery diameter, a decrease in forearm vascular resistance, and an improvement in aortic distensibility. The other arterial segments studied did not show any significant changes. Our results suggest that the long-lasting arterial effects of the ACE inhibitor ramipril are partly pressure independent and are related to effects on arterial tone that may reduce the cardiovascular abnormalities associated with hypertension.

Angiotensin II↗
PubMed1991

Long lasting arterial effects of the ACE inhibitor ramipril.

The aim of this study was to determine the acute and chronic arterial effects of the ACE inhibitor, ramipril. Fourteen patients (mean age 47 years) with mild to moderate essential hypertension completed the study. A first haemodynamic examination was performed at the end of a 15-day placebo period (D15) before and 3 hours after oral administration of ramipril, 5 mg. Then all the patients started a 4-week treatment with ramipril, 5 mg/day. At the end of this period (D42) the haemodynamic examination was repeated 24 hours after the last capsule intake, and then 3 hours after administration of ramipril 5 mg. Brachial and carotid artery haemodynamics were evaluated by a bidimensional pulsed Doppler system. Arterial distensibility was non-invasively studied in three different arterial segments (carotido-femoral, brachio-radial, femoro-tibial) by the evaluation of the pulse wave velocity. Ramipril significantly decreased BP after acute or chronic administration. Chronic treatment with ramipril was followed by a long lasting increase in brachial artery diameter, a decrease in forearm vascular resistance, and an improvement in aortic distensibility. The other investigated arterial segments did not show any significant changes. Our results suggest that long lasting arterial effects of the ACE inhibitor ramipril are partly pressure-independent and are related to an effect of this drug on arterial tone. These effects may be able to reduce the hypertensive cardiac and arterial abnormalities.

Adult↗
PubMed1990

Vascular effects of intravenous infusion of the angiotensin converting enzyme inhibitor perindoprilat.

This study was aimed at evaluating the hemodynamic changes after acute inhibition of the renin-angiotensin system in hypertensive patients. Twenty-one subjects with essential hypertension were randomized into three groups of seven subjects each. In group I, the direct vascular vasodilator dihydralazine was administered at a dose of 4 micrograms/kg per min. Groups II and III received a continuous intravenous infusion of the angiotensin converting enzyme (ACE) inhibitor perindoprilat at a dose of 1 microgram/kg per min and 2.5 micrograms/kg per min, respectively. Brachial artery hemodynamics and aortic distensibility were evaluated non-invasively. Vascular reactivity was evaluated by the cold-pressor test. In all three groups, an identical decrease in blood pressure was observed (P less than 0.001), followed by a slight (but not significant) decrease in the heart rate in both perindoprilat groups, and an important tachycardia in the dihydralazine group (P less than 0.001). Brachial artery diameter was increased in the high-dose perindoprilate group from 0.437 +/- 0.014 to 0.479 +/- 0.013 cm (P less than 0.02), but remained unchanged in the two other groups. No significant changes in brachial artery mean blood velocity and blood flow were observed. In group III, aortic distensibility increased almost twice as much as in the two other groups, but this difference was not statistically significant. The pressor response to the cold-pressor test was not modified in the three groups; the heart rate response was almost completely abolished in groups II and III, but increased in the dihydralazine group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Haemodynamic effects of perindopril in essential hypertension.

Blood pressure, forearm arterial haemodynamics and echocardiographic parameters were studied in patients with sustained essential hypertension before and after administration of the ACE inhibitor, perindopril. In a single blind study versus placebo, perindopril significantly reduced BP and at the same time increased brachial artery diameter, blood flow and compliance. As part of the haemodynamic investigation, a 5 minute wrist occlusion was performed. During this period, blood flow velocity and arterial diameter decreased but the reduction in diameter was smaller with perindopril after one year's treatment showing an increase in brachial artery diameter. This result indicates that the increase in brachial arterial diameter following perindopril could not be explained solely on the basis of a flow dependent dilation. When perindopril was withdrawn after three months of treatment and replaced by placebo for four weeks, BP and forearm arterial haemodynamics returned towards baseline values. However, cardiac mass which was significantly decreased after perindopril remained decreased four weeks after cessation of treatment. In the seven normalised patients, perindopril was continued for one year; arterial compliance remained increased and cardia mass diminished. The study showed that the arterial changes caused by perindopril involved a drug-related relaxation of arterial smooth muscle and that there was a differential response in cardiac and arterial changes following long term treatment.

Adult↗
PubMed1989

[Hemodynamic effects of perindopril].

1. The effects of prolonged infusion of perindopril (1 mg/kg/d) were studied on Goldblatt rats and spontaneously hypertensive SHR rats compared to control animals. Perindopril increased significantly the arterial compliance in treated animals. Mechanical parameters of the carotid artery are normalized with perindopril infusion in renovascular hypertensive rats and improved in SHR rats. Perindopril reversed the thickness of aortic media in treated rats. After three months treatment the ratio elastine/collagen of the aortic media increased significantly. Perindopril reversed the majority of vascular alteration in both hypertensive groups. 2. Twenty one hypertensive patients received for 30 minutes an infusion of perindoprilat either at 1 mg/kg/min, or at 2.5 mg/kg/min, or dihydralazine at 4 mg/kg/min. It was shown that perindoprilat significantly reduced the blood pressure in the three groups. However the increase in arterial diameter and compliance were only recorded with perindoprilat (2.5 mg/kg/min) infusion. The results of this study pointed out that for the same antihypertensive effect, with two different antihypertensive drugs, the vascular effects can be different. Blood pressure, forearm hemodynamic parameters, echocardiography values were recorded on 16 sustained hypertensive patients before and after one year of perindopril treatment. The results showed that perindopril decreased significantly the SBP, DBP and the MBP, increased diameter and arterial compliance of the brachial artery, and decreased cardiac mass. Three months later, the treatment was stopped for four weeks: blood pressure and hemodynamic values returned toward basal values, whereas mass cardiac didn't increase significantly; then the treatment was continued over 9 months; during this period. The arterial compliance increased again on the cardiac mass remained reduced. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗