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Biomedical subjects

M E Safar

Publications and source records attributed to M E Safar.

At least 73 records · Page 4Linked to original sources
PubMed1999

Differences in aortic response to vasoactive stimuli in Japanese and Lyon rats. The role of hypertension.

OBJECTIVE: We have previously shown that conduit arteries of normotensive (WKY) and hypertensive (SHR) Japanese rats differ from normotensive (LN) and hypertensive (LH) Lyon rats in terms of lower aortic thickness and higher collagen III content, whereas differences in vasoactive properties are unknown. METHODS: Aortic rings with (E+) and without (E-) endothelium were studied under resting and noradrenaline-stimulated conditions in the presence of N(omega)-nitro-L-arginine (L-NNA) alone or in association with indomethacin, bosentan and/or BQ123. RESULTS: Under resting conditions, aortas of normotensive and hypertensive Japanese rats differed from Lyon rats by higher developed tension in the presence of L-NNA and endothelium. In the absence of endothelium, normotensives differed from hypertensives in terms of stronger developed tensions in the presence of L-NNA in the two strains. Addition of indomethacin to L-NNA induced relaxation in E+ SHR and E- WKY and contraction in E-LH. By contrast, tensions were unchanged after addition of bosentan and BQ123. Under stimulated conditions, tensions were equally increased by L-NNA in E+ and unchanged in E- both in Japanese and Lyon rats whether they were normotensive or hypertensive, and indomethacin (but not bosentan) elicited higher response in Lyon than in Japanese rats in E+ and E- aorta. CONCLUSION: Under NO synthase inhibition, the vasoactive properties of Japanese and Lyon aorta differ in the presence of a cyclo-oxygenase blocker but not endothelin blockers. These results indicate that the aorta vasorelaxant tone is associated to prostanoid regulation in Lyon but not in Japanese rats. This observation appears dependent on the genetic and/or environmental background linked to the origin and not the presence of hypertension.

Animals↗
PubMed1999

Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients.

Large artery damage is a major contributory factor to cardiovascular morbidity and mortality of patients with hypertension. Pulse wave velocity (PWV), a classic evaluation of arterial distensibility, has never been ascertained as a cardiovascular risk marker. To determine the factors influencing aortic PWV and the potential predictor role of this measurement, we studied a cohort of 710 patients with essential hypertension. Atherosclerosis alterations (AA) were defined on the basis of clinical events. Calculation of cardiovascular risks, by use of Framingham equations, was performed in subjects without AA. PWV was higher in the presence of AA (14.9+/-4.0 versus 12.4+/-2.6 m/s, P<0.0001), even after adjustments on confounding factors and was the first determinant (P<0.0001) of the extent of atherosclerosis assessed as the sum of the atherosclerotic sites. In patients without AA, all cardiovascular risks increased constantly with PWV. Furthermore, at a given age, aortic PWV was the best predictor of cardiovascular mortality. The odds ratio of being in a high cardiovascular mortality risk group (>5% for 10 years) for patients in the upper quartile of PWV was 7.1 (95% confidence intervals 4.5 to 11.3). The presence of a PWV >13 m/s, taken alone, appeared as a strong predictor of cardiovascular mortality with high performance values. This study shows that aortic PWV is strongly associated with the presence and extent of atherosclerosis and constitutes a forceful marker and predictor of cardiovascular risk in hypertensive patients.

Age Factors↗
PubMed1999

Plasma homocysteine, aortic stiffness, and renal function in hypertensive patients.

Hyperhomocysteinemia has been associated with both vascular structure alterations and vascular clinical end points. To assess the relation between plasma homocysteine, structure and function of large arteries, and the presence of clinical vascular disease, we investigated a population of 236 hypertensive patients. We estimated arterial stiffness by measuring the carotid-femoral pulse wave velocity. Total plasma homocysteine was determined by fluorometric high-performance liquid chromatography. The presence of cardiovascular disease was defined on the basis of clinical events, including coronary heart disease, cerebrovascular disease, and peripheral vascular disease. In this population, pulse wave velocity was positively correlated with homocysteine, even after adjustments for age, mean blood pressure, extent of atherosclerosis, and creatinine clearance (P=0.016). Analysis of variance showed statistically significant differences between the mean values of homocysteine, creatinine clearance, and pulse wave velocity according to the extent of atherosclerosis, with an increase in these 3 parameters concomitant with an increase in the number of vascular sites involved with atherosclerosis. In conclusion, in hypertensive patients the levels of homocysteine are strongly and independently correlated to arterial stiffness measured by aortic pulse wave velocity. Plasma homocysteine, creatinine clearance, and aortic pulse wave velocity are higher in patients presenting with clinical vascular disease. These results suggest that the evaluation of aortic distensibility and homocysteine levels can help in cardiovascular risk assessment in hypertensive populations.

Adult↗
PubMed1999

Changes in arterial structure and function under trandolapril-verapamil combination in hypertension.

BACKGROUND AND PURPOSE: Converting enzyme inhibition and calcium blockade alter large arteries in hypertension. However, the heterogeneity of the response according to the site of cardiovascular measurements has never been investigated. METHODS: In a double-blind study, we compared for 180 days 3 hypertensive patient groups treated with verapamil, trandolapril, or their combination. Using echo-Doppler technique and applanation tonometry, we independently measured mean pressure, local pulse pressure, arterial diameter, and distensibility at 3 arterial sites (brachial and common carotid arteries and abdominal aorta), as well as cardiac and carotid wall structure. RESULTS: Mean and pulse pressure decreased significantly to a greater extent with the drug combination. Regarding arterial and cardiac hemodynamics, significant and similar changes were noted in the 3 groups: decreases in abdominal aorta and carotid but not brachial diameter; increases in carotid artery, abdominal aorta, and brachial distensibility even after adjustment to mean blood pressure reduction; and more substantial regression of cardiac mass than carotid wall thickness. CONCLUSIONS: This study shows that both compounds and more significantly combination therapy decreased mean and pulse pressures measured independently and that the changes in diameter, thickness, and stiffness were influenced primarily by the site of cardiovascular measurements, resulting in a predominant increase in distensibility of muscular arteries, little change in carotid wall thickness, but a significant regression of cardiac hypertrophy.

Adult↗
PubMed1999

[Mechanism of action of cicletanine on the relationship between endothelium and vascular smooth muscle in the rat thoracic aorta under normoxic and hypoxic conditions].

OBJECTIVE: The vascular mechanism of action of cicletanine, an antihypertensive agent, was studied on isolated Wistar rat aorta in presence and in absence of endothelium both in normoxic and hypoxic conditions. DESIGN AND METHODS: Isolated aorta, from 24 month-old rats, were precontracted with noradrenaline (10(-7) M), in presence and in absence of endothelium and exposed to cumulative cicletanine concentrations in presence and absence of either L-NNA (10(-4) M) or indomethacin (Indo) (10(-7) M). Thereafter, aorta were precontracted by noradrenaline 10(-7) M, and hypoxia was induced by switching gas mixture from 95%O2/5%CO2 to 95%N2/5%CO2 during 10 minutes. Results are expressed as mean +/- sem and statistical analysis were done using one-way analysis of variance. RESULTS: When aorta were precontracted with noradrenaline (10(-7) M), in presence of endothelium, cicletanine (10(-9)-10(-4) M), induced a biphasic concentration-dependent relaxation (EC50 approximately 10(-7) M and 3 x 10(-5) M). In absence of endothelium, the effect of cicletanine was abolished (10(-9) and 10(-5) M). Whereas, at higher concentration (10(-4) M), the magnitude of the relaxation reached 94 +/- 2% and 67 +/- 5% of the initial developed tension in presence and in absence of endothelium respectively. The endothelium-dependent relaxation induced by cicletanine was significantly reduced by Indo (10(-7) M) (p < 0.05) and L-NNA (10(-4) M) (p < 0.005). Addition of 10 mM of BaCl2 significantly reversed the relaxation induced by the higher concentration of cicletanine used (p < 0.005). Under hypoxic conditions, the aorta, in presence of endothelium, displayed an increased developed tension which was significantly attenuated by cicletanine. CONCLUSION: These results indicated that cicletanine relaxes vascular smooth muscle through both, an endothelium-dependent action which was mediated by cyclooxygenase and NOsynthase pathways and an endothelium-independent action that was mediated through K+ channels opening. Under hypoxic conditions, our findings indicate that the effects of cicletanine, appear related to an endothelium protective action associated to NO release.

Animals↗
PubMed1999

Large arteries in hypertension. Pharmacological and therapeutic aspects.

The blood pressure curve may be divided into two components: mean arterial pressure, the steady component, and pulse pressure, the pulsatile component. Whereas pharmacological interventions in hypertension have been focused mainly on mean arterial pressure, little has been done to reduce selectively pulse pressure. However, increased pulse pressure with nearly normal mean arterial pressure is the classical hallmark of systolic hypertension in the elderly and a strong independent predictor of cardiac mortality, mainly for myocardial infarction. In this report, after the analysis of the factors influencing pulse pressure, a review of the pharmacological agents susceptible to reduce this hemodynamic factor is performed.

Arteries↗
PubMed1999

Epidemiological aspects of pulse pressure and arterial stiffness.

Systolic and diastolic blood pressure are considered to be exclusive haemodynamic predictors of cardiovascular risk in humans. If high blood pressure is characterized as a mechanical factor which acts on the arterial wall with deleterious consequences, then the totality of the blood pressure curve should be investigated to determine the risk. The purpose of this review is to show that, in addition to systolic and diastolic blood pressure, other haemodynamic variables should be taken into account; namely, brachial pulse pressure, pulse pressure amplification, aortic pulse wave velocity, and carotid incremental elastic modulus. These new components might modify our conventional views on antihypertensive agents and may serve to identify new potentially active molecules.

Antihypertensive Agents↗
PubMed1998

Effects of norepinephrine on the mechanical properties of the human radial artery in vitro.

BACKGROUND: The human radial artery has been proposed as an alternative to coronary grafts in subjects with coronary ischemic disease. Because this muscular artery is known to be prone to spasm, changes in its mechanical properties in response to catecholamines are important to investigate. METHODS: We describe a new echo-tracking technique of high resolution that allows investigation, in vitro, of the diameter and the wall thickness of arterial cylindrical segments. In addition, a classic tissue bath experiment is used to study the vasoreactivity of arterial rings. Mechanical properties of the radial artery are determined over a 0 to 200 mm Hg range of transmural pressure in the presence and absence of norepinephrine in the perfusion medium. RESULTS: With tissue bath experiments, the norepinephrine dose-response curve was characterized by an EC50 value of 1.48+/-1.09 10(-6) mol/L and a maximal developed tension at 10(-5) mol/L. The results obtained with pressurized segments gave similar results with an EC50 value of 8.1+/-2.3 10(-7) mol/L and a maximal change in diameter at 10(-5) mol/L norepinephrine. Under the influence of 10(-5) mol/L norepinephrine, the radial artery constriction reached 22%, significantly affecting the unstressed diameter. Compliance did not show any significant change in the overall transmural pressure range, whereas distensibility significantly increased and elastic modulus significantly decreased. CONCLUSION: The study shows that the capacitive properties of the human muscular radial artery are maintained with norepinephrine not only through decreased stiffness of wall material but also through reduced unstressed diameter. Thus drugs inducing smooth muscle relaxation may be helpful in preventing radial artery spasm after coronary grafts.

Aged↗
PubMed1998

Differential responses of the heart and vasculature to chronic blood pressure reduction in essential hypertension.

BACKGROUND: In subjects with hypertension, converting enzyme inhibitors and calcium entry blockers may decrease arterial stiffness independently of blood pressure changes, but the heterogeneity of response of the arterial tree has never been taken into account. MATERIAL AND METHODS: In 31 subjects with hypertension, we determined through the use of Doppler echographic techniques the compliance and distensibility of the common carotid and femoral arteries and of the abdominal aorta, the radial artery wall thickness, and cardiac mass. In a double-blind randomized study, the converting enzyme inhibitor ramipril and the calcium entry blocker nitrendipine were studied and compared during 12 weeks treatment, then 4 weeks after treatment was stopped. RESULTS: The two drugs caused significantly different plasma levels of active renin, angiotensin I, and norepinephrine but the same effects on blood pressure, cardiac mass, radial artery wall thickness, and stiffness indices. In contrast, the effect of treatment differed substantially according to the site of cardiovascular measurements. Although cardiac mass decreased significantly in parallel with blood pressure reduction, no change in radial artery wall thickness occurred. Carotid compliance and distensibility increased significantly, even after drug treatment was stopped, whereas little or no change was observed for the femoral artery and the abdominal aorta. CONCLUSION: This study provides evidence that the changes in cardiovascular structure and function with ramipril and nitrendipine treatment are poorly influenced by their different mechanisms of action but highly dependent on the site of measurements. The results suggest that local autocrine-paracrine mechanisms act synergistically with blood pressure to produce cardiovascular changes.

Adult↗
PubMed1998

Influence of body height on pulsatile arterial hemodynamic data.

OBJECTIVES: This study sought to present evidence that short stature is a hemodynamic liability, which could explain in part the inverse relation between body height and cardiovascular risk. BACKGROUND: Other explanations for the association of short stature with increased cardiovascular risk include advancing age, reduced pulmonary function, genetic factors, poor childhood nutrition and small-caliber coronary arteries. This study adds another factor-the physiologic effects of reduced body height on the arterial tree, which increase left ventricular work and jeopardize myocardial perfusion. METHODS: Four hundred two subjects were studied: 149 with end-stage renal disease and 253 with normal renal function. Measurements included blood pressure, body height, cardiac cycle length, carotid to femoral artery pulse wave velocity, carotid artery pulse waves (by applanation tonometry) and the arrival time of reflected waves. Calculations included the carotid augmentation index, carotid artery compliance and the diastolic to systolic pressure-time ratio (an index of myocardial supply and demand). RESULTS: On linear and stepwise multiple regression, body height correlated with all variables except mean blood pressure. CONCLUSIONS: The early systolic arrival of reflected waves in short people in this group acts to stiffen the aorta and increase the pulsatile effort of the left ventricle, even at the same mean blood pressures. Short stature also induces a faster heart rate, which increases cardiac minute work and shorten diastole. Stiffening lowers the aortic diastolic pressure and, coupled with a shortened diastole, could adversely influence myocardial supply. Although indirect, this evidence supports a physiologic hypothesis for the body height-cardiovascular risk association.

Adolescent↗
PubMed1998

Increased arterial distensibility in postmenopausal hypertensive women with and without hormone replacement therapy after acute administration of the ACE inhibitor moexipril.

Menopause and essential hypertension are associated with a decreased compliance and distensibility of the arteries. ACE inhibitors have been shown to improve arterial distensibility. Hormone replacement therapy (HRT), especially estrogens, could have a positive influence through their atheroprotective, vasodilative, and blood pressure-lowering effect. The vascular interactions of HRT and ACE inhibitors, like moexipril hydrochloride, have not been investigated so far. This trial was intended to assess the effect of combined sequential HRT for 25 days on acute changes in arterial distensibility after a single oral dose of 15 mg moexipril hydrochloride in postmenopausal women with borderline to mild essential hypertension. This study had a monocentric, randomized, parallel-group design, and was open for moexipril, and double-blind, and placebo-controlled for HRT. Assessment of arterial distensibility was by automatic noninvasive measurement of the carotid-femoral pulse wave velocity (PWV). The PWV and the pulse pressure decreased significantly after a single oral dose of 15 mg moexiprill. An influence of HRT on the changes in the PWV and pulse pressure could not be seen. The plasma concentrations of renin increased and of aldosterone decreased after moexipril administration. Arterial function improves after acute administration of 15 mg moexipril in postmenopausal women with mild to moderate essential hypertension. The changes in PWV and pulse pressure are of similar magnitude in women with and without HRT.

Aldosterone↗
PubMed1998

Endothelin and cardiovascular remodelling in end-stage renal disease.

BACKGROUND: Plasma endothelin (ET) is elevated in end-stage renal disease (ESRD), but the origin and consequences of this increase remain unclear. In the present study we analysed the relationships between plasma ET levels and cardiovascular alterations in ESRD. METHODS AND RESULTS: Common carotid artery (CCA) intima-media thickness (IMT) and diameter, atherosclerotic plaque occurrence, and left ventricular (LV) geometry and function were determined by ultrasound imaging in 76 haemodialysis patients and in 57 age-, sex-, and blood pressure-matched controls. Arterial stiffness was evaluated via carotid-femoral pulse wave velocity (CF-PWV), forearm post-ischaemic vasodilation was measured by venous plethysmography, and plasma ET levels were determined using a specific immunoenzymoassay. Compared with controls, ESRD patients had elevated plasma ET levels (1.6 +/- 1.4 vs 4.6 +/- 3.8 pg/ml; P < 0.001), increased LV mass (P < 0.001), increased CCA-IMT (P < 0.001), a higher prevalence of atherosclerotic plaques (P < 0.001) and increased CF-PWV (P < 0.01). Plasma ET levels correlated positively with LV outflow velocity integral (r = 0.57; P < 0.0001), stroke index (P < 0.01), and baseline forearm blood flow (P < 0.001) which were all significantly higher in ESRD patients than in controls (P < 0.01). After adjustment for age, blood pressure, haemoglobin levels, gender and body dimensions, plasma ET levels were significantly correlated to LV mass (r = 0.46; P < 0.001), CCA-IMT and CCA intima-media cross-sectional area (r = 0.41; P < 0.001), and CF-PWV (P < 0.05). Post-ischaemic forearm vasodilation was decreased in ESRD (85 +/- 31 vs 119 +/- 28%; P < 0.001) and there was a negative correlation between post-ischaemic flow recovery and ET levels (r = -0.49; P < 0.001). In ESRD patients, plasma ET levels were positively and independently correlated with the prevalence of CCA atherosclerotic plaque (P < 0.01). CONCLUSIONS: These results indicate that the increased plasma ET levels in ESRD patients are associated with left ventricular hypertrophy and arterial intima-media thickening, suggesting that increased ET concentrations in ESRD patients may be of pathophysiological significance in the process of cardiovascular remodelling.

Adaptation, Physiological↗
PubMed1998

Large artery structure and function in hypertension and end-stage renal disease.

The cardiovascular complications in hypertension are ascribed to two different but associated alterations, namely atherosclerosis and arteriosclerosis. Whereas the former disturbs principally the conduit function and the delivery of an adequate blood flow to peripheral organs and tissues, the latter disturbs the cushioning function of large arteries, inducing an inadequate increase in systolic and pulse pressure. Arteriosclerosis represents a clinical form of accelerated ageing process and is characterized by a diffuse dilation and hypertrophy of large conduit arteries and stiffening of arterial walls. Independently from the ageing, structural changes are associated with several haemodynamic alterations such as increased in blood flow and flow velocity, and increased parietal stress due to increased arterial diameters and/or intraarterial pressure. The principal consequences of arterial stiffening are: (1) an increased left ventricular afterload with development of left ventricular hypertrophy and increased myocardial oxygen demand; (2) altered coronary perfusion and blood flow distribution; and (3) decreased perfusion reserve during haemodynamic stress. In the absence of controlled studies, it is difficult to propose therapeutic interventions aimed to prevent or treat arterial abnormalities in hypertensive patients. It has been shown that long-term administration of either calcium channel blockers and angiotensin converting enzyme inhibitors led to an improvement of vessel wall elasticity. Nevertheless, these studies did not conclude whether the improvement of elastic properties were due only to decrease in blood pressure or to alterations in intrinsic properties of arterial walls. More investigations should be necessary to investigate this important problem.

Animals↗
PubMed1998

Effects of a chronic high-salt diet on large artery structure: role of endogenous bradykinin.

Bradykinin activity could explain the blood pressure increase during NaCl loading in hypertensive animals, but its contribution on vascular structure was not evaluated. We determined cardiac mass and large artery structure after a chronic, 4-mo, high-salt diet in combination with bradykinin B2-receptor blockade by Hoe-140. Four-week-old rats were divided into eight groups according to strain [spontaneously hypertensive rats (SHR) vs. Wistar-Kyoto (WKY) rats], diet (0.4 vs. 7% NaCl), and treatment (Hoe-140 vs. placebo). In WKY rats, a high-salt diet significantly increased intra-arterial blood pressure with minor changes in arterial structure independently of Hoe-140. In SHR, blood pressure remained stable but 1) the high-salt diet was significantly associated with cardiovascular hypertrophy and increased arterial elastin and collagen, and 2) Hoe-140 alone induced carotid hypertrophy. A high-salt diet plus Hoe-140 acted synergistically on carotid hypertrophy and elastin content in SHR, suggesting that the role of endogenous bradykinin on arterial structure was amplified in the presence of a high-salt diet.

Animals↗
PubMed1998

Venous and arterial behavior during normal pregnancy.

To assess the contribution of the arterial and venous systems in the hemodynamic changes of normal pregnancy, we studied blood flow, vascular resistance, venous tone, and the viscoelastic properties ("creep") of the upper and lower limbs (using plethysmography), aortic distensibility (using pulse wave velocity measurements), and cardiac dimensions (using echocardiography) in nine healthy women. Studies were longitudinally performed at the first (10-13 wk) and third (33-38 wk) trimesters of pregnancy in comparison with the period between the third and sixth month after delivery. From the first trimester, heart rate significantly increased while systemic blood pressure and limb vascular resistances did not change significantly and aortic distensibility increased (P < 0.05). Lower limb viscoelastic properties decreased at the third trimester (P < 0.05) and venous tone increased from the first trimester (P < 0.01), whereas little changes were observed at the site of upper limbs. The decrease in calf venous tone was significantly correlated with the increase in left ventricular diastolic diameter at the first (P < 0.001) and the third trimester (P < 0.05). The study provides evidence that during normal pregnancy, changes in the arterial and venous sides of the circulation occur independently of pressure alterations. The increase in venous tone, contributing to preload augmentation, and the decrease in aortic stiffness, reducing afterload, both optimize cardiac function until delivery.

Adult↗
PubMed1998

Arterial response during cold pressor test in borderline hypertension.

We observed previously that sympathetic activation produced by lower body negative pressure increases pulse-pressure amplification with little change in mean pressure. Whether the cold pressor test (CPT) might produce a similar hemodynamic pattern has been ignored. Ten subjects with borderline hypertension and ten age- and sex-matched normotensive controls were compared to investigate carotid-brachial pulse-pressure amplification (aplanation tonometry) and changes in brachial and carotid distensibility (echotracking technique) before and during CPT. The maneuver markedly increased blood pressure without a change in heart rate. Pulse-pressure amplification tended to disappear as a consequence of a higher increase in carotid than in brachial pulse pressure, due to an earlier return of wave reflections at the carotid site. CPT caused a significant decrease in carotid and brachial distensibility. Both results were more pronounced in controls than in borderline hypertensives. Thus CPT reduces pulse-pressure amplification. In humans, this change may greatly influence the calculation of arterial distensibility, although this point is usually minimized in animal experiments. Furthermore, in young subjects, sympathetic stimulus may induce different arterial responses, depending on the mechanism involved: reflex or global nonspecific stimulus.

Adult↗
PubMed1998

Quantification of sympathetic and parasympathetic tones by nonlinear indexes in normotensive rats.

Because the use of spectral powers of blood pressure (BP) and R-R interval (RR) in the low (LF) and high frequencies (HF) to quantify sympathetic and parasympathetic activities is still under debate, we questioned whether nonlinear methods may give better results. The BP signal was recorded for 30 min before and after intravenous injection of hexamethonium (20 mg/kg), atropine (0.5 mg/kg), atenolol (1 mg/kg), and prazosin (1 mg/kg) in conscious, normotensive Wistar-Kyoto rats. Three nonlinear indexes [percentage of recurrence, percentage of determinism, and length index (Lmax)] extracted from the recurrence plot method were used to analyze the BP signal. Sympathetic but not parasympathetic blockade reduced BP level and its LF component. RR increased and decreased after beta- and alpha-blockades, respectively. Hexamethonium increased HF, and atropine reduced LF, of RR. Sympathetic blockade and, in particular, alpha-sympathetic blockade increased nonlinear indexes of BP. In contrast, parasympathetic blockade by atropine increased nonlinear indexes of RR. These results suggest that, compared with spectral indexes, nonlinear indexes may be more specific markers of sympathetic and parasympathetic tones.

Animals↗