Search PubMed⌕ Search

Biomedical subjects

A Benetos

Publications and source records attributed to A Benetos.

At least 91 records · Page 5Linked to original sources

Acute and long-term effects of angiotensin converting enzyme inhibition on larger arteries and cardiac hypertrophy: mechanical and structural parameters.

AIM OF STUDIES: The extent of cardiovascular alterations in hypertension is related quantitatively to the degree of hypertension. However, there is increasing evidence that humoral processes, which are not dependent on blood pressure, are of major importance in these alterations. In particular, angiotensin converting enzyme (ACE) activity seems to be involved. We therefore compared the effects of blood pressure reduction and of acute and long-term ACE inhibition on cardiac hypertrophy, arterial function and morphologic alterations in hypertension. ACUTE STUDY: To examine the acute effect of ACE inhibition on arterial compliance, we used an experimental model allowing a pressure-volume determination in the carotid artery in situ to assess arterial compliance in normotensive Wistar-Kyoto and spontaneously hypertensive rats. The pressure-volume relationship was determined after an acute, single, oral administration of either placebo or the ACE inhibitor quinapril in doses of 0.3 and 3 mg/kg. Both doses of quinapril produced a similar relaxation of arterial smooth muscle, approximately 80-90% of the maximum relaxation produced by potassium cyanide. LONG-TERM STUDY: We then studied the long-term effects of ACE inhibition compared with those of hydralazine. Four groups of 4-week-old spontaneously hypertensive rats were treated for 4 months with quinapril at 1 or 10 mg/kg per day, hydralazine at 15 mg/kg per day or placebo. Blood pressure, plasma and aortic ACE activity, left ventricular weight and histomorphometric parameters of the thoracic aorta, the renal and the mesenteric arteries were evaluated. We found a marked dissociation between the effects on blood pressure and cardiovascular structural parameters. Whereas both hydralazine and 10 mg/kg quinapril prevented the development of hypertension and aortic hypertrophy in a pressure-dependent manner, only the ACE inhibitor prevented left ventricular hypertrophy and aortic collagen accumulation. These quinapril effects were observed even with a small non-antihypertensive dose (1 mg/kg); the effect on aortic collagen was related to a reduction in aortic but not plasma ACE. CONCLUSIONS: These results indicate that the acute and long-term effects of ACE inhibitors on arterial function and structure go well beyond their antihypertensive actions and seem to be related to inhibition of tissue ACE. However, while clear effects were observed in the particular arterial segment explored, it may not be valid to extrapolate these findings to other arterial segments.

Angiotensin-Converting Enzyme Inhibitors↗

Sodium, large arteries, and diuretic compounds in hypertension.

Clinical and experimental data have shown that antihypertensive drugs do not cause the same change in arterial compliance for an equipotent blood pressure reduction. However, there is not clear data on the effect of sodium and diuretics on the visco-elastic properties of the hypertensive arterial wall. Cross-sectional epidemiologic studies suggest that, at any given value of age and blood pressure, pulse wave velocity is lower in the presence of decreased sodium intake. Longitudinal studies indicate that, in hypertensive subjects, low sodium intake is associated with a larger brachial artery diameter than is high sodium intake. In hypertension in the elderly and in severe hypertension with end-stage renal disease, sodium overload causes a reduction in arterial compliance and distensibility unrelated to blood pressure changes. In animal studies, the diuretic compounds cycletanine and indapamide were shown to increase systemic and carotid compliance independently of blood pressure changes. In contrast, a crossover study of hypertensive subjects showed that the diuretic agent hydrochlorothiazide did not change arterial compliance and pulse wave velocity, whereas the calcium entry blocker, felodipine, improved these parameters. Nevertheless, indapamide decreased the pulse pressure on stroke volume ratio, a parameter used as a marker of aortic distensibility. Taken together, such studies indicate that sodium may act on the arterial wall independently of blood pressure changes. The contribution of counter regulatory mechanisms, possibly related to the renin-angiotensin and sympathetic nervous systems, might explain the differences between the clinical and experimental changes observed with diuretic compounds. Of the various antihypertensive agents, diuretics seem to have the least effect on the arterial system.

Animals↗

[Regional arterial hemodynamics and carotid circulation in essential arterial hypertension. Effect of nitrendipine in patients over 40 years of age].

Lesions of the arterial wall constitute one of the main complications of essential hypertension. The final objective of all antihypertensive drugs is to reduce the cardiovascular morbidity and mortality rates, but their short and medium term objectives must be to normalise blood pressure values and to correct the functional and structural abnormalities consecutive to arterial hypertension. In this double-blind drug versus placebo study conducted in 20 patients (14 men, 6 women) aged over 40, the effects of nitrendipine on regional arterial haemodynamics (aortic territory, upper limb, lower limb) and carotid circulation were evaluated. Nitrendipine was administered daily in doses of 20 mg during 1 month. After 4 weeks of treatment, the treated group showed a fall in blood pressure and an improvement in the pulse wave propagation (an index of arterial distensibility) in the carotido-femoral territory (11.4 +/- 1.7 vs 9.9 +/- 1.6 m/s; P < 0.01) and in the humero-radial territory (12.9 +/- 2.0 vs 11.6 +/- 2.1 m/s; P < 0.05); there was no change in the femoro-tibial territory (13.2 +/- 1.8 vs 12.5 +/- 1.7 m/s; NS). The haemodynamics of the common carotid artery showed no change in carotid diameter or blood velocity, and small lowering of local resistances (28.1 +/- 9.1 vs 24.6 +/- 4.9 mmHg.s.ml-1; P < 0.05). This study demonstrates that in patients older than 40 years a long-term treatment with nitrendipine lowers blood pressure, does not alter the common carotid flow and improves arterial distensibility. The arterial effects seem to vary according to the arterial territories considered.

Adult↗

Comparison of effects of felodipine versus hydrochlorothiazide on arterial diameter and pulse-wave velocity in essential hypertension.

In a double-blind cross-over study, the arterial changes produced by hydrochlorothiazide were compared with those observed after the calcium antagonist felodipine in 16 patients with mild to moderate systemic hypertension. Diameter changes at the site of the common carotid and brachial arteries were investigated using pulsed Doppler velocimetry, and pulse-wave velocities of the aortic, brachial and femorotibial areas were measured using standard noninvasive techniques. Whereas hydrochlorothiazide and felodipine similarly decreased blood pressure, hydrochlorothiazide did not change pulse-wave velocity, and the diameters of the brachial and common carotid arteries. Felodipine significantly decreased pulse-wave velocity, and increased brachial arterial diameter and compliance, with no change in carotid arterial diameter. Evidence was found that although felodipine had specific effects on the arterial system of hypertensive subjects, hydrochlorothiazide did not produce any sizable arterial change. These differential effects may influence specifically the heart afterload, with important consequences for diuretics that are known to cause minimal changes in cardiac structure and function.

Adult↗

Positive correlation between the blood pressure and heart rate response to the cold pressor test and the environmental temperature in older hypertensives.

The aims of our study were to evaluate whether there is any relationship between the environmental temperature and the response to the cold pressor test and if this relationship is different in younger and older hypertensive patients. We studied 100 mild-to-moderate hypertensives, aged 21 to 75 years. In the > or = 45 years group (46 patients) a significant positive correlation between the environmental temperature and the heart rate and blood pressure response to the cold pressor test was found. The relative humidity was not correlated with the response to the cold pressor test, but multiplying the mean temperature and the mean relative humidity enhanced the correlations of the environmental temperature. An increase in the mean temperature for the 20 days before the cold pressor test (the best correlated period) by 10 degrees C correlated with increases in the systolic blood pressure response by 10.5 mm Hg (P = .0195), the diastolic blood pressure response by 8 mmHg (P = .0079), the mean blood pressure by 9 mmHg (P = .0058), and the heart rate response by 3.8 beats/min (P = .0134). In < 45 years patients no environmental relationship of the response to cold pressor test was found. A chronic exposure to low temperatures is correlated with higher blood pressure levels--as previously reported--and, in contrast (but only in elderly), with a lower blood pressure response to acute cold stress. Our findings confirm the higher meteorological dependence of hemodynamics in the elderly, and suggest that the research protocols using the cold pressor test should adjust the response for the previous environmental temperature.

Adult↗

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↗

Endogenous bradykinin activity in Dahl rats.

We assessed the participation of endogenous bradykinin (BK) on basal blood pressure (BP) regulation in anesthetized Dahl-sensitive (DS) and Dahl-resistant (DR) rats receiving different NaCl diets. Four groups of Dahl rats were studied after 5 weeks of high (H) = 7% or low (L) = 0.4% NaCl diet (DSH, n = 9; DSL, n = 11; DRH, n = 9; DRL, n = 10). Endogenous BK activity was assessed with a continuous intraarterial (i.a.) infusion of the specific BK antagonist (B4146 100 micrograms/kg/min) for 10 min. Sensitivity to exogenous BK was tested 30 min after the end of the infusions, with bolus intraarterial (i.a.) injections of BK (0.1, 0.5, 1, and 5 micrograms). DSH had a significantly higher (p < 0.0001) basal mean BP (MBP) as compared with the three other groups: DSH = 185 +/- 7 mm Hg (mean +/- SEM), DSL = 143 +/- 5 mm Hg, DRH = 132 +/- 10 mm Hg, and DRL = 134 +/- 6 mm Hg. BK antagonist infusion increased MBP by 13.2 +/- 1.5 mm Hg in DSL rats, by 6.8 +/- 1.6 mm Hg in DRL, by 4.7 +/- 1.6 mm Hg in DRH, and by 1.1 +/- 8 mm Hg in DSH. Statistical analysis showed that the high NaCl diet significantly decreased the response to the BK antagonist in DS (p < 0.001) but not in DR rats. MBP response to exogenous BK was similar in all groups. These results show that endogenous BK has a vasodepressor effect on DS rats fed a low NaCl diet. This effect is suppressed after a high-salt diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

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↗

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↗

[Effects of aging on arterial function in man].

The structure of arteries changes with age. Gradual disappearance of elastic fibres facilitates dilatation of the arterial lumen and increase in length of the vessels. Simultaneously, the arterial wall becomes thicker, but it is often difficult to distinguish the changes due to ageing from those caused by atherosclerosis. These structural alterations result in a greater rigidity of the arteries, which can now be evaluated by non-invasive segmental methods. This shows that ageing does not have the same functional effects on wide-caliber elastic arteries and on middle-sized muscular arteries. The increase of systolic arterial pressure observed in the elderly is a consequence of structural and functional changes in the arterial system.

Aged↗

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↗

Arterial effects of salt restriction in hypertensive patients. A 9-week, randomized, double-blind, crossover study.

OBJECTIVE: To investigate the hemodynamic effects of a moderately low-salt diet in a 9-week, randomized, double-blind, crossover study in 20 hypertensive, ambulatory patients. METHODS: All subjects followed a 9-week, low-salt diet. During this period, they received capsules containing either lactose or salt in 4-week treatment periods, separated by a 1-week washout period. Hemodynamic and biological parameters were evaluated on the day of randomization and at the end of weeks 4 and 9. We defined a low-sodium diet (LSD) as a salt-restriction period with lactose capsules, and a normal-sodium diet (NSD) as a salt-restriction period with capsular salt supplementation. RESULTS: Blood pressure was significantly lower during LSD compared with NSD. This fall in blood pressure was associated with a decrease in peripheral resistance in carotid and forearm circulation. Brachial artery diameter was larger during LSD whereas carotid artery diameter remained unchanged. The changes in brachial artery were: (1) not related to blood pressure changes; (2) positively related to age, and (3) negatively correlated with baseline intracellular sodium content. CONCLUSIONS: These results suggest that moderate low-salt restriction is capable of decreasing blood pressure and peripheral resistance in carotid and forearm circulation. The increase in brachial, but not carotid, artery diameter following salt restriction suggests a difference in salt dependence among different arteries.

Adult↗

Mechanism of nitrate-induced improvement on arterial compliance depends on vascular territory.

The link between arterial caliber and distensibility has been studied extensively, with conflicting results. As have other researchers, we previously showed evidence of an increase in arterial diameter and a decrease in arterial stiffness with use of nitrates at the site of the brachial artery (BA) and the aorta. Whether these results would apply to other large superficial arteries remained to be established. In the present study, by means of an original pulsed ultrasound echo-tracking system based on Doppler shift, we measured internal diastolic diameter and stroke change in diameter of the common carotid artery (CCA), the femoral artery, and the BA in patients with essential hypertension and determined the acute effects of administration of isosorbide dinitrate (ISDN 20 mg). Twenty untreated hypertensive patients entered this randomized, placebo-controlled, double-blind, parallel study. No significant change occurred during placebo. During ISDN therapy, blood pressure (BP) decreased significantly; cross-sectional compliance increased at the site of the CCA, the BA, and the common femoral artery (CFA). The increase in cross-sectional compliance was mainly due to an increase in internal diameter for CCA and to an increase in distensibility coefficient (DC) for BA. The pattern of cross-sectional compliance was intermediate for CFA. During ISDN therapy, the augmentation index of the CCA distension waveform was significantly reduced, whereas no change occurred during placebo, suggesting a reduction in wave reflection by nitrates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Arterial and antihypertensive effects of nitrendipine: a double-blind comparison versus placebo.

Arterial effects evaluated by carotid-femoral, brachial-radial, and femoral-tibial pulse wave velocity and antihypertensive effect evaluated by 24-h ambulatory blood pressure (BP) monitoring were measured in 17 hypertensive patients before and 24 h after once-daily nitrendipine (20 mg) administration. After a 15-day placebo period, a double-blind study of nitrendipine versus placebo was performed for 1 month. After nitrendipine dosing, BP measured by sphygmomanometer 24 h after the last drug intake showed a significant decrease as compared with the pretreatment period. Ambulatory BP mean values were also significantly decreased for systolic and diastolic BP (SBP, DBP). This decrease predominated during the day but was observed nocturnally only after 6 a.m. Twenty-four hours after the last tablet intake of nitrendipine, carotid-femoral and brachial-radial pulse wave velocities were significantly reduced, whereas femoral-tibial wave velocity was unchanged, indicating that markers of arterial rigidity might be substantially modified and that the modifications were partly unrelated to BP changes. The results provide evidence that in hypertensive subjects nitrendipine 20 mg given once daily for 1 month produces an arterial effect for 24 h, in association with BP reduction.

Adult↗

Increased systolic pressure in chronic uremia. Role of arterial wave reflections.

To assess the role of arterial wave reflections in the mechanism of systolic hypertension and altered pulsatile arterial dynamics in patients with end-stage renal disease (ESRD), 79 ESRD patients were compared with 73 age-matched control subjects with normal renal function and similar mean blood pressure. Wave reflections were investigated from the carotid pulse contour recorded by applanation tonometry using a Millar micromanometer-tipped probe. Wave reflections were quantified as the ratio (augmentation index, %) of the height of the late systolic peak to the total height of carotid pulse wave. Travel time of the reflected wave was timed from the foot of the pressure wave to the foot of the late systolic peak. Systolic and pulse pressure were increased in ESRD patients (p less than 0.001) and was not attributable to differences in left ventricular ejection pattern. The augmentation index was increased in ESRD patients (23.2 +/- 15.0 versus 9.8 +/- 15.6%; p less than 0.001) in association with a shorter travel time of reflected wave (109 +/- 24 versus 131 +/- 30 msec; p less than 0.001). Multiple regression analysis showed two principal factors associated (p less than 0.001) with the increase in augmentation index and shortened travel time of reflected wave: increased aortic pulse wave velocity and smaller stature with shorter body height in ESRD patients. The study points to the role of arterial wave reflections in the mechanisms producing alterations in pulsatile arterial dynamics in ESRD and is the first, through the mechanisms of early wave reflections, to show in humans that the increase in systolic and pulse pressures is associated with lesser body size.

Adult↗

An indirect evaluation of the effect of the autonomic nervous system following converting enzyme inhibition in hypertension.

Common carotid blood flow and cold pressor test were evaluated in 16 patients with sustained essential hypertension before and after 30 days treatment with the converting enzyme inhibitor Enalapril (20 mg). Enalapril decreased blood pressure and carotid vascular resistance with no significant change in heart rate. After treatment, despite a wide range of the responses, the changes in systolic blood pressure to cold test were significantly attenuated, whereas the heart rate responses were not. Acute random and double blind administration of either Cadralazine or Nitrendipine, two vasodilating drugs which are known to cause an activation of the autonomic nervous system, were performed before and after long term treatment by Enalapril. Whereas the blood pressure and heart rate responses to cold test was unmodified by these compounds before Enalapril treatment, significant changes were observed after converting enzyme inhibition: Cadralazine reduced the heart rate response whereas Nitrendipine increased it significantly. The study provides evidence that converting enzyme inhibition causes sympatho-inhibitory influences which are principally observed in stress conditions, with heterogeneous responses depending on the nature and the type of stimulation.

Adult↗

Vascular endothelium, mechanical properties of the arterial wall and local angiotensin converting enzyme inhibition.

METHODS: An experimental model of in situ isolated carotid arteries was used to study the contribution made by angiotensin II (Ang II) towards the mechanical properties of the arterial wall in 12-week-old Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. The effects of local incubation with saralasin (Sar1-Thr8-Ang II, 10(-6) mol/l) and with lisinopril (5 x 10(-6) mol/l) on carotid compliance were compared to the effects of removing the endothelium and the effects of totally abolishing vasomotor tone with potassium cyanide (0.1 mg/ml). RESULTS: With an intact endothelium, local incubation with lisinopril increased carotid compliance by 23% in WKY rats (P less than 0.05) and by 14% in SHR (P less than 0.01). Under the same experimental conditions, saralasin increased carotid compliance by 24% in WKY rats and 23% in SHR relative to control values (P less than 0.05 and P less than 0.001, respectively). Removal of the endothelium induced significant increases in carotid compliance in WKY rats (17%, P less than 0.01) and in SHR (33%, P less than 0.001). After removal of the endothelium, there was no further increase in carotid compliance with lisinopril in either strain. In contrast, saralasin induced further significant compliance increases in both strains (+18%, P less than 0.001, and +11%, P less than 0.01, in WKY and SHR, respectively). After the artery had been poisoned with potassium cyanide, there was no further increase in compliance relative to values obtained with saralasin in either strain with or without the endothelium. CONCLUSIONS: These findings suggest that Ang II receptors have a major effect on the control of basal vasomotor tone of large arteries in both normotensive and hypertensive rats. Furthermore, the increase in carotid compliance induced by local incubation with saralasin and with angiotensin converting enzyme (ACE) inhibitors may involve similar mechanisms acting on smooth muscle angiotensin receptors.

Angiotensin II↗