Biomedical subjects

M E Safar

Publications and source records attributed to M E Safar.

At least 145 records · Page 8Linked to original sources

PubMed1993

Long-term effects of angiotensin-converting enzyme inhibition on the arterial wall of adult spontaneously hypertensive rats.

The effects of long-term angiotensin-converting enzyme (ACE) inhibitor treatment with perindopril 2 mg/kg/day, by gavage, for 3 months on the mechanical function and structure of large arteries were studied in adult spontaneously hypertensive rats with established hypertension. Hemodynamic parameters, including instantaneous aortic blood flow and pressure, were recorded under anesthesia at the end of the treatment period. Systemic arterial compliance was calculated from aortic pressure and flow recordings; passive mechanical properties of the in situ localized carotid artery were measured. Histologic and morphologic parameters of the aortic media, including cross-sectional area and thickness, size, and density of smooth muscle nuclei and of elastin and collagen fibers, were measured using an automated image analysis system. ACE inhibitor treatment significantly decreased mean arterial pressure (-27%, p < 0.001) and total peripheral resistance (-30%, p < 0.05) while cardiac output was increased (29%, p < 0.05). Systemic arterial compliance and carotid compliance were both increased by treatment (63%, p < 0.05, and 83%, p < 0.05, respectively). Morphometric assessment of vascular structure showed that ACE inhibitor treatment significantly decreased medial cross-sectional area (-36%, p < 0.001) and thickness (-16%, p < 0.001) by affecting smooth muscle cell hypertrophy (nucleus size decreased by 26%, p < 0.05) without changes in smooth cell number. Collagen density was decreased by treatment (-42%, p < 0.05), whereas elastin density was not affected by treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

Hemodynamic changes in elderly hypertensive patients.

Hypertension in the elderly is characterized by a disproportionate increase of systolic blood pressure over diastolic blood pressure. Subsequently, in this category of patients, the increase in pulse pressure predominates over the increase in mean arterial pressure, thus highlighting the role of arterial changes in this pattern of hemodynamics. In the presence of normal or reduced cardiac function, the disproportionate increase in systolic pressure is the result of a combination of increases of both arterial stiffness and wave reflections. The former is primarily due to central aortic structural changes with a small contribution by modifications of the smooth muscle tone of the central large arteries. The latter is secondary to the geometric modifications of the arterial system associated with age that are responsible for the increase in wave reflections within the thoracic aorta as a consequence of increases in pulse wave velocity and in reflection points closer to the heart.

Aged↗

PubMed1993

Role of endothelium in the mechanical response of the carotid arterial wall to calcium blockade in spontaneously hypertensive and Wistar-Kyoto rats.

OBJECTIVES: Calcium blockade has been reported to inhibit the contraction of the vascular smooth muscle and the liberation of vasoactive substances by endothelial cells. We tested the effects of calcium blockade on the mechanical properties of the carotid artery in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) in the presence and in the absence of endothelium. METHODS: The pressure-volume relationships of isolated carotid arteries were recorded in situ in SHR (n = 20) and WKY rats (n = 20) before and after calcium blockade by local incubation with clentiazem. RESULTS: With intact endothelium, calcium blockade induced a significant shift in the pressure-volume curve in both strains, volume being significantly higher after calcium blockade than under control conditions. In WKY rats the carotid mechanical properties were similar after calcium blockade and after abolition of the smooth muscle tone by potassium cyanide (KCN) poisoning. In SHR the carotid compliance measured after incubation with clentiazem was significantly lower than that measured after KCN poisoning. Removal of the endothelium induced a significant shift in the pressure-volume curve towards the volume axis in both strains, and an increase in carotid compliance. Local incubation with clentiazem or KCN did not induce further modifications of the pressure-volume relationship either in WKY rats or in SHR. Furthermore, in SHR and WKY rat carotid arteries, the pressure-volume relationship and the compliance measured after incubation with clentiazem were identical in the presence and in the absence of endothelium. CONCLUSIONS: In WKY rat and SHR carotid arteries, acute calcium blockade increases the arterial compliance independently of the endothelium integrity. Furthermore, part of the compliance enhancement induced by the calcium antagonist could be related to an antagonizing mechanism of the production of endothelial constricting factor or factors.

Animals↗

PubMed1993

Pulse pressure gradient along the aortic tree in normotensive Wistar-Kyoto and spontaneously hypertensive rats: effect of nicardipine.

BACKGROUND: In large animals pulse pressure increases from central to peripheral arteries whereas mean arterial pressure decreases slightly. This haemodynamic pattern has not been verified in small animals, particularly in hypertensive rats before and after administration of antihypertensive drugs. DESIGN: The intra-arterial blood pressure of normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) was determined along the aorta in anaesthetized and conscious rats. In anaesthetized rats the study was performed before and after acute intravenous nicardipine administration (30 micrograms/kg). RESULTS: Mean arterial pressure was significantly higher in untreated SHR than in WKY rats, and within each strain was quite similar along the aortic tree. Pulse pressure increased significantly from the central to the terminal aorta in WKY rats, principally due to an increase in systolic blood pressure. In SHR pulse pressure did not differ along the aortic tree. Compared with in WKY rats, aortic pulse pressure in SHR was significantly elevated whereas femoral pulse pressure was quite similar. Acute nicardipine administration re-established the pulse pressure gradient in SHR, due to a significant decrease in central aortic pulse pressure with no significant change in femoral pulse pressure. CONCLUSIONS: These results suggest, first, that since there are large differences in pulse pressure in the proximal aorta of SHR and WKY rats but only small or negligible differences in the distal aorta, the measurement of pulse pressure may be an available index to differentiate normotensive and hypertensive rats, and secondly, that increased aortic pulse pressure in SHR participates in the increase in cardiac afterload independently of mean arterial pressure, and may be a preferential site of action of antihypertensive agents.

Animals↗

PubMed1993

Microgravity and orthostatic intolerance: carotid hemodynamics and peripheral responses.

A ground-based model [24 h of bed rest (BR) with head-down tilt (HDT)] was used to investigate the cardiovascular deconditioning responsible for orthostatic intolerance, frequently observed after weightlessness flights. This experimental deconditioning is shown to be distinguished by an increase of mean blood pressure (P < 0.05), with increased total peripheral resistances (TPRs). Systolic tangential tension of the carotid arterial wall, cardiac output and frequency (spectral analysis), and plasma norepinephrine and epinephrine were not significantly altered, while plasma dopamine was increased (P < 0.05). Cardiovascular homeostasis was challenged before and after 24 h of BR with HDT through -40 mmHg lower body negative pressure (LBNP). Systolic tangential tension of the carotid wall was decreased, with a decrease of systolic pressure and cardiac output; increased heart rate was likely due to an increase of sympathetic drive with a decrease of vagal braking. The overall picture was not changed after 24 h of BR with HDT, except for a lack of increase of TPRs: their increase (+13.7%, P < 0.05) before was no longer observed after (-2.6%) 24 h of BR with HDT. This apparent deficiency cannot be explained. However, a heterogeneity in the response of TPR should be considered because the magnitude of the increase of blood pressure to cold pressor test was the same after 24 h of BR with HDT as it was before.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Role of adrenergic tone in mechanical and functional properties of carotid artery during aging.

The present study was designed to assess the role of the adrenergic tone in the regulation of carotid arterial compliance during aging. An experimental model of in situ isolated carotid arteries has been used to evaluate the elastic properties of the arterial wall in young (3-mo-old) and older (18-mo-old) Wistar rats. Binding experiments were performed in the same strain of rats to evaluate alpha 1- and beta-adrenoceptor affinity and density. In a third set of experiments, structural parameter of the carotid artery in younger and older rats was evaluated. Arterial distensibility (compliance per unit of volume) was significantly lower in older rats. This was associated with a significant thickness of the media (45.6 +/- 2.8 vs. 57.5 +/- 5.7 microns, P < 0.01) and increased collagen content in older rats (4,420 +/- 310 vs. 7,320 +/- 850 microns 2/mm, P < 0.001). However, carotid arterial compliance was not altered in older rats because of the significant increase in cross-sectional area with aging. Aging did not affect alpha 1-adrenoceptor affinity and density, whereas it decreased beta-density without changing their affinity. Pharmacological stimulation of alpha 1-adrenoceptor with phenylephrine (10(-5) M) decreased compliance in older but not in younger animals. Blockade of these receptors with prazosin or labetalol increased compliance in younger and had no effect on older rats. beta-receptor stimulation with isoproterenol or blockade with propranolol had no effect in any of the studied groups. We suggest that with aging there is an increased vasoconstricting effect of alpha-agonists and a decreased vasodilatative action of alpha-blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1993

Hypertension in primary chronic glomerulonephritis analysis of 359 cases.

The incidence of hypertension was evaluated in 359 patients with primary chronic glomerulonephritis who underwent renal biopsy. It was compared to a control group of 7,468 subjects who were obtained from an epidemiologic study performed in the same area at the same period. The prevalence of hypertension was 42%. On the basis of multiple regression analysis, the level of blood pressure was shown to be positively correlated to four independent variables: age, body mass index, degree of renal insufficiency and presence of proliferative glomerulonephritis. It was concluded that, although renal insufficiency increases the incidence of hypertension, proliferative lesions play an important contributive role in the development of hypertension.

Adolescent↗

PubMed1993

Arterial alterations with aging and high blood pressure. A noninvasive study of carotid and femoral arteries.

Noninvasive in situ evaluations of pulsatile changes of blood pressure and arterial diameter were performed at the sites of the common carotid and femoral arteries in a population of 78 untreated normotensive and hypertensive subjects. Arterial segments were studied by using an original echo-tracking technique for internal diameter and validated applanation tonometry for local pulse pressure measurements. Whereas mean arterial pressure is known to be identical in all parts of the arterial tree, pulse pressure was significantly lower in the carotid (52.7 +/- 2.2 mm Hg) than in the brachial (62.0 +/- 2.0 mm Hg) or femoral (62.5 +/- 2.5 mm Hg) arteries. Despite a higher pulse pressure and diastolic diameter, the femoral artery had a lower pulsatile change in diameter (3.47 +/- 0.18% versus 6.07 +/- 0.28%; p < 0.0001) and distensibility coefficient (9.36 +/- 0.58 versus 21.60 +/- 1.75 x 10(-3) kPa-1) than the carotid artery. Local cross-sectional compliance of the carotid artery was higher than that of the femoral artery (7.42 +/- 0.46 versus 6.20 +/- 0.28 m2.kPa-1.10(-7); p < 0.05). Whereas age was strongly correlated with arterial parameters at the site of the carotid artery (pulse pressure: r = 0.54, p < 0.0001; pulsatile change in arterial diameter: r = -0.62, p < 0.0001; distensibility coefficient: r = -0.70, p < 0.0001), no significant correlation was observed at the femoral artery. Mean blood pressure was the second factor of carotid artery alterations: the higher the mean blood pressure, the lower the distensibility of this artery (r = -0.36, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Wave reflections and cardiac hypertrophy in chronic uremia. Influence of body size.

Arterial wave reflections (AWRs), an important determinant of cardiac afterload, are increased in hemodialysis patients. However, an association between AWRs and left ventricular hypertrophy has not been established in these subjects. We therefore sought an association between these two parameters in a cross-sectional study of two outpatient hemodialysis populations. AWRs were quantified (augmentation index, percent) as the ratio of the height of the late systolic peak to the total height of the carotid pulse wave recorded with a micromanometer-tipped probe. AWRs were determined in 44 hemodialysis patients, 22 with pronounced AWRs (group A: augmentation index > 12%), and 22 with small or moderate AWRs (group B: augmentation index < 12%). The groups were matched for age, sex, blood pressure, and hemodialysis duration. Left ventricular size was determined by echocardiography. Despite lower body size (P < .005) and similar blood pressure, cardiac output, peripheral resistance, and aortic pulse wave velocity, group A patients had greater left ventricular mass (P < .01). For the population as a whole, left ventricular mass and AWRs were positively correlated (P < .0001) independent of age, blood pressure, hemodialysis duration, or body size. Lesser body height was the principal factor associated with increased AWRs in group A (P < .001). We conclude that in hemodialysis patients AWRs are associated with the development of left ventricular hypertrophy and that small body height is a risk factor for long-term cardiovascular complications.

Adult↗

PubMed1993

Mechanical function and histological structure of the arterial wall. The response to antihypertensive treatment.

Alterations in the structure and function of large arteries could be a major factor in the mortality and morbidity of hypertensive patients. This paper summarises the effects of various pharmacological treatments on the mechanical (functional) properties of large arterial walls and on the structure and composition of these vessels. Firstly, during arterial hypertension, increases in arterial stiffness, associated with medial hypertrophy and/or hyperplasia and alterations in extracellular matrix, are always observed. Sodium intake and aging may influence the arterial wall properties, causing an increase in stiffness, independently of their effect on blood pressure. In parallel, administration of low doses of diuretics to hypertensive rats did not cause significant haemodynamic changes, but did cause an increase in arterial distensibility. Nitrates and derivatives have specific effects on the smooth muscle from large arteries in hypertensive patients. Significant increases in the diameter of large arteries and in arterial wall stiffness have been reported in clinical studies, but these effects have a short time constant. In humans and animals, angiotensin converting enzyme (ACE) inhibitors and calcium antagonists cause relaxation of arterial smooth muscle and, therefore, improve the functional component of the reduced distensibility observed in hypertension. Long term treatment with ACE inhibitors and calcium antagonists induces a significant reduction in medial hypertrophy. However, it is difficult to distinguish between the direct effects resulting from pressure reduction and a specific drug effect.

Animals↗

PubMed1993

Behaviour of conduit arteries in hypertension.

Through an increase in vascular resistance, changes of the small arteries are responsible for the evaluation of mean arterial pressure in hypertension. However, the amplitude of the pressure oscillation, i.e. pulse pressure, is influenced by other hemodynamic mechanisms, which involve large arteries through a decrease in compliance and an increase in wave reflections. Consequently, structural and functional alterations of the large arteries are responsible in hypertensive subjects for an increase in the amplitude of the pressure oscillation and a disproportionate increase in systolic pressure over diastolic blood pressure through arterial (and not arteriolar) changes. Such findings not only contribute to a better understanding of the relationships between vascular structure and function and the level of blood pressure but also to better interprate the hypertensive complications, particularly those related to the heart and larges vessels.

Animals↗

PubMed1993

Twenty four hours head-down tilt decreases arterial baroreflex function in conscious rat.

In human zero gravity induces a cardiovascular deconditioning. The transfer of blood from the periphery to the thoracic compartment, occuring immediately at the beginning of the exposure to microgravity seems to be involved in this phenomenon. We have previously shown that LBNP (-40 mm Hg) produced an exaggerated heart rate response at the end of 24 hours of bed rest without modification of the cardiopulmonary receptors in human. Some other studies have shown that microgravity induces an impairment of the baroreflex sensitivity in human, but its involvement in the cardiovascular deconditioning is not completely understood. The aim of this study was to determine the modification of the arterial baroreflex using a model of simulated weightlessness in conscious rats during the exposure to microgravity.

Animals↗

PubMed1992

Large artery dilation produced by converting enzyme inhibition in hypertension: therapeutic aspects.

Large artery dilation is produced by angiotensin-converting enzyme inhibition in hypertensive subjects despite a significant blood pressure reduction. The resulting increase in arterial compliance may be due both to blood pressure decrease and to arterial smooth muscle relaxation. In healthy volunteers and in hypertensive subjects, dosages causing large artery dilation seem to be higher than those causing pure arteriolar dilation with resulting blood pressure reduction. Similar findings have been noted to obtain compliance enhancement. Such results may be important in considering antihypertensive therapy, particularly when remodeling of the cardiovascular system is considered in long-term treatment.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1992

Hypertension in the elderly.

Publication of the SHEP study (Systolic Hypertension in the Elderly Programme) leaves no doubt that isolated systolic hypertension in the elderly should be treated. There are, however, a number of important outstanding questions: (a) the mechanism of reduction of morbidity, (b) because antihypertensive therapy appears to be more effective in elderly patients than in the young, when should treatment be started in relation to progression of age?, (c) besides the blood pressure elevation, what are the exact mechanical factors responsible for degeneration of the arterial wall?, and (d) what in 1993 is the definition of hypertension? These are questions that now need to be answered.

Aged↗

PubMed1992

Hysteresis of the venous pressure-volume relationship in the forearm of borderline hypertensive subjects.

1. The forearm venous pressure-volume relationship was studied in 14 young men with borderline hypertension and in 16 control subjects of the same age and sex. Strain-gauge plethysmography was used to evaluate volume changes after slow increases and decreases in distention, in order to estimate the amplitude of the hysteresis curve. 2. Compared with normotensive control subjects, subjects with borderline hypertension had significantly higher values of blood pressure, heart rate and forearm blood flow. 3. Baseline forearm venous tone was slightly, but not significantly, increased in borderline hypertensive subjects (21.35 +/- 6.53 versus 18.75 +/- 5.95 mmHg ml-1 100 ml-1) and was significantly enhanced after a cold pressor test. The increase was no higher in the borderline hypertensive subjects than in the normotensive control subjects. 4. The area of the hysteresis curve was significantly decreased (7.58 +/- 3.58 versus 10.34 +/- 5.67 arbitrary units; P = 0.0092) as was the extent of isotonic relaxation (creep) (0.28 +/- 0.11 versus 0.39 +/- 0.22 ml/100 ml; P = 0.0098) in borderline hypertensive subjects compared with control subjects. Both parameters were unaffected by the cold pressor test. 5. The study suggests that the viscous component of the venous wall is altered in young patients with borderline hypertension, indicating intrinsic changes in vascular segments which are not exposed to increased intraluminal pressure.

Adult↗

PubMed1992

Carotid arterial haemodynamics after mild degrees of lower-body negative pressure in man.

1. Pulsatile changes in the diameter of the common carotid artery were studied transcutaneously using an echo-tracking technique in 15 normal subjects: eight subjects before and during application of graded lower-body negative pressure from -5 to -15 mmHg, and seven subjects before and during weight-bearing head-up tilt at 30 and 60 degrees. 2. In concomitant studies of changes in forearm vascular resistance, it was seen that mild lower-body negative pressure produced deactivation of cardiopulmonary receptors without changes in systemic blood pressure or heart rate. 3. After lower-body negative pressure, a significant decrease in carotid arterial diastolic diameter [from 0.662 +/- 0.028 to 0.624 +/- 0.033 cm (lower-body negative pressure -10 mmHg) and 0.640 +/- 0.030 cm lower-body negative pressure -15 mmHg), P < 0.001 and < 0.05] was observed. 4. After head-up tilt, carotid arterial diameter was also significantly decreased at 30 and 60 degrees, whereas a significant increase in heart rate occurred only at 60 degrees and mean blood pressure did not change. 5. The study provides evidence that the geometry of the arterial wall is substantially modified by non-invasive manoeuvres such as head-up tilting and lower-body negative pressure. The latter is assumed to selectively deactivate human cardiopulmonary receptors, but the present data suggest that local changes may also influence carotid baroreceptors.

Adult↗

PubMed1992

Ambulatory blood pressure measurement, smoking and abnormalities of glucose and lipid metabolism in essential hypertension.

OBJECTIVE: Casual (mercury sphygmomanometer) and ambulatory blood pressure measurements were determined in 61 subjects with sustained essential hypertension. DESIGN: Patients were classified into three subgroups: smokers or non-smokers; patients with or without hyperglycemia; and patients with or without plasma lipoprotein abnormality. Mean casual blood pressure were shown to be identical in these three subgroups. RESULTS: When ambulatory blood pressure was analyzed, smokers exhibited a significant increase in pulse pressure exclusively during the activity period, whereas diastolic blood pressure and mean arterial pressure (MAP) were not modified in comparison with controls. Patients with abnormal plasma glucose showed a significant increase in systolic and pulse pressure during both activity and non-activity periods, with a slight increase in MAP during the activity period. Patients with and without plasma lipid abnormality displayed similar ambulatory blood pressure. CONCLUSION: The study provides evidence that, in spite of similar casual blood pressure levels among smokers and non-smokers, as well as among those with elevated fasting glucose levels, smokers and patients with hyperglycemia have a higher systolic and pulse pressure during 24-h monitoring, pointing to the possible role of cyclic stress in the deterioration in the structure of the hypertensive arterial wall.

Blood Glucose↗

PubMed1992

Arterial structure in hypertension and the effects of angiotensin converting enzyme inhibition.

BACKGROUND: In hypertension, structural changes in the cardiovascular system affect not only small arteries and the heart but also the large arteries, particularly in elderly people. It has been suggested that structural alterations to the small arteries are responsible for the elevation in mean arterial pressure seen in hypertension, as a result of increased vascular resistance. However, the amplitude of pressure oscillation (pulse pressure) is influenced by other haemodynamic mechanisms that involve large arteries including a decrease in compliance and an increase in wave reflection. EFFECTS OF STRUCTURAL ALTERATIONS TO LARGE ARTERIES ON BLOOD PRESSURE: Structural alterations to the large arteries may, in hypertensive subjects, be responsible for an increase in the amplitude of pressure oscillation, leading to a disproportionate increase in systolic over diastolic blood pressure because of arterial (not arteriolar) changes. These findings not only contribute to a better understanding of the relationship between vascular structure and blood pressure levels but also to a better interpretation of hypertensive complications, particularly those related to the heart and large vessels. APPLICATION TO TREATMENT: The reversal of structural arterial changes may become a goal in long-term antihypertensive treatment. Angiotensin converting enzyme (ACE) inhibitors in particular can reverse structural arterial changes, increase arterial compliance and produce a more pronounced decrease in systolic than in diastolic blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗