Mechanical properties and structure of carotid arteries in mice lacking desmin.

OBJECTIVE: Our aim was to determine in desmin homozygous mutant mice the viscoelastic properties, the mechanical strength and the structure of the carotid artery. METHODS: To assess the viscoelastic properties of large arteries, we have performed an in vivo analysis of the diameter-, and distensibility-pressure curves of the common carotid artery (CCA) in homozygous (Des -/-), heterozygous (Des +/-) and wild-type (Des +/+) mice. To evaluate the mechanical strength, we have measured the in vitro intraluminal pressure producing the rupture of the carotid artery wall. The structure analysis of the arterial wall was based on histology and electronic microscopy. RESULTS: A lower distensibility and an increase of arterial wall viscosity were observed in Des -/- compared with Des +/+. Arterial thickness of Des -/- was similar to those of Des +/+, without changes in elastin and collagen contents. Electron microscopy revealed that the perimeter of cellular fingerlike-projections was smaller in Des -/-, indicating that the cells have lost part of their connections to the extracellular matrix. The rupture pressure was significantly lower in Des -/- (1500+/-200 mmHg) compared with Des +/+ (2100+/-80 mmHg) indicating a lower mechanical strength of the vascular wall. No significant difference was found between Des +/- and Des +/+. CONCLUSION: The desmin is essential to maintain proper viscoelastic properties, structure and mechanical strength of the vascular wall.

Smooth muscle tone and arterial wall viscosity: an in vivo/in vitro study.

The relationships between steady and pulsatile pressures, smooth muscle tone, and arterial viscoelastic behavior remain a matter of controversy. We previously showed that arterial wall viscosity (AWV) was 3-fold lower in vivo than in vitro and suggested that in vivo active mechanisms could minimize intrinsic AWV to improve the efficiency of heart-vessel coupling energy balance. The aim of the present study was to determine the role of smooth muscle tone on AWV, under various levels of steady and pulsatile pressures, both in vivo and in vitro. AWV of rat abdominal aorta was studied first in vivo after bolus injections of phenylephrine (PE) or sodium nitroprusside (SNP), then in vitro in response to PE or SNP. In vitro, arterial segments were submitted first to steady pressure (0 to 200 mm Hg) by increments of 20 mm Hg, then to increasing levels of pulse pressure (20 to 50 mm Hg) at various mean arterial pressures (75 to 150 mm Hg). AWV was quantified as the area of the pressure/diameter relationship hysteresis, issued from the simultaneous measurements of pressure (Millar micromanometer) and diameter (NIUS echotracking device). In vivo, AWV increased after PE and decreased after SNP, in parallel with pressure changes. In vitro, AWV was not significantly influenced by PE and SNP. After both PE and SNP, AWV increased with pulse pressure but was not influenced by mean arterial pressure. At any given pulse pressure, AWV was higher in vitro than in vivo. The relation between AWV and pulse pressure was significantly steeper in vitro than in vivo. These results show that AWV is strongly influenced by steady and pulsatile mechanical load but not by smooth muscle tone, both in vivo and in vitro. Factors other than sustained smooth muscle activation should be explored to explain the minimization of AWV in vivo compared with intrinsic in vitro values.

Aortic distensibility and structural changes in sinoaortic-denervated rats.

The purpose of the present study was to determine the effects of chronic sinoaortic denervation on the mechanical properties and composition of the abdominal aorta in Wistar rats. We used a high-resolution echotracking system to determine in situ under physiological conditions of blood flow and arterial wall innervation the aortic diameter-, compliance-, and distensibility-pressure curves in 16-week-old anesthetized rats that had been denervated at 10 weeks of age for 6 weeks (n = 8). Compared with sham-operated rats (n = 8) we observed a marked reduction of baroreflex response and increase in overall mean blood pressure variability as measured by standard deviation and spectral analysis in sinoaortic-denervated rats. Mean blood pressure was not affected by sinoaortic denervation in both conscious and anesthetized rats. Sinoaortic denervation significantly shifted the distensibility-pressure curve toward lower levels of distensibility, indicating a decreased aortic distensibility for a given level of arterial pressure. Sinoaortic denervation produced a significant increase of aortic wall cross-sectional area and collagen content, one of the less-distensible components of the arterial wall. These results suggest that intact arterial baroreceptors are necessary for maintaining normal functional and structural properties of large arteries in rats. The reduction in arterial distensibility in chronic sinoaortic-denervated rats may have resulted from different factors, including the initial hypertensive phase, aortic wall hypertrophy, and increase in collagen content. The changes in aortic wall structure and related reduction in aortic distensibility, in addition to other mechanisms, might have been direct consequences of an increased blood pressure variability.

Influence of graded changes in vasomotor tone on the carotid arterial mechanics in live spontaneously hypertensive rats.

1. The contribution of vasomotor tone to the increased stiffness of carotid arteries in living spontaneously hypertensive rats (SHR) is largely unknown. Whether a reduced vascular tone is associated with an increase or a decrease in arterial stiffness in vivo remains to be determined. The goal of the present investigation was to show that a decrease in vascular tone is associated with a decrease in arterial stiffness, independent of the structural composition of the arterial wall. 2. New high resolution echo-tracking techniques were used to evaluate pulsatile changes of carotid blood pressure and diameter following transient and graded changes of vasomotor tone produced by the dihydropyridine derivative, isradipine. Treatment for 8 weeks was given to groups of SHR rats either with a low (0.6 kg day-1) or a high (2.6 mg kg-1 day-1) dose. Another SHR group received an acute dose of 2.6 mg kg-1 day-1. Results were compared to those of placebo-treated Wystar-Kyoto (WKY) and SHR rats. Whatever the dosage, acute or chronic calcium blockade caused a decrease in blood pressure which was maximal 1 h after administration and disappeared after the 16th h. Carotid arterial thickness and the composition of the arterial wall was determined from histomorphometry. 3. In placebo-treated SHR, the inverse relationship relating blood pressure to carotid arterial distensibility was significantly shifted toward higher values of blood pressure compared to the curve of normotensive placebo-treated WKY rats. The curve of SHR receiving chronically a non antihypertensive (0.6 mg kg-1 day-1) isradipine dose prolonged that of placebo-treated SHR toward lower values of blood pressure, so that carotid distensibility was significantly higher than in WKY for the same diameter and blood pressure level (145 mmHg). With administration of a chronic antihypertensive dose (2.6 mg kg-1 day-1) causing a significant decrease in arterial function. Acute antihypertensive calcium blockade with a single isradipine dose (2.6 mg kg-1 day-1) caused a similar shift in the pressure-distensibility curve toward the WKY curve although the histomorphometric composition of the arterial wall differed significantly from that of chronically treated animals. 4. The study provides evidence that, in living SHR submitted to calcium blockade, (i) a low dose of isradipine causing no substantial antihypertensive effect is associated with a significant elevation of carotid arterial distensibility for the same pressure and diameter as normotensive controls, and (ii) an acute or chronic dose causing a substantial antihypertensive effect is associated with a transient shift of the SHR distensibility-pressure curve toward a physiological arterial function, increasing carotid distensibility for the same pressure and diameter as WKY controls. Since such findings were observed independently of the histomorphometric composition of the arterial wall, they imply that the transient decrease in arterial stiffness produced by calcium blockade should involve specific changes in the connections between arterial smooth muscle and extracellular matrix.

Optimizing ultrasonic transducers based on piezoelectric composites using a finite-element method.

A novel approach to understanding the vibratory behavior of composite piezoelectric materials is proposed. Elementary ceramic rods, and the effects of their width-to-thickness (W/T) ratio are studied. A model based on the finite-element methods is used. Some experimental results that agree well with the computed data are presented. Plots of resonant frequencies and coupling coefficients versus W/T are given that can be used in transducer design.

[Arterial compliance is not diminished in hypertensive patients when compared at the same level of blood pressure]. / La compliance artérielle n'est pas diminuée chez l'hypertendu lorsqu'elle est comparée à même niveau de pression artérielle.

Whether the decrease in large artery compliance, observed in hypertensive patients (HT), is due to an increase in distending pressure or to intrinsic alterations of the vascular wall remains much debated. We determined the diameter-pressure curve of the common carotid artery over the systolic-diastolic range, then derived the compliance-pressure curve, in order to compare arterial compliance in normotensive subject (NT) and in HT, for a common level of distending blood pressure: 100 mmHg (isobaric compliance). Fourteen NT and 15 never treated essential HT were included in the study. The diameter-pressure curve of the common carotid artery was determined non-invasively by simultaneously and continuously recording the systolic-diastolic changes in internal diameter (using a high resolution echotracking system) and pressure waveform (using high fidelity applanation tonometry on the contralateral artery) over 4-6 cardiac cycles. The level of MAP of the carotid pressure waveform was determined electronically and set equal to mean brachial pressure. Compliance-pressure curve was then derived from the pressure-diameter curve in order to determine compliance (C) for any given level of blood pressure, particularly MAP (CMAP) and 100 mmHg (C100). Despite the considerable differences in blood pressure, the compliance-pressure curve of HT was not different from that of NT. CMAP decreased with aging (p < 0.001) and MAP (p < 0.001). According to age, CMAP was reduced in HT as compared to NT (84 +/- 49 vs 116 +/- 52 mm2.mmHg.10(-3) p < 0.01). C100 decreased with aging (p < 0.05) but not with MAP. According to age, C100 was not reduced in hypertensives.(ABSTRACT TRUNCATED AT 250 WORDS)

Intrinsic stiffness of the carotid arterial wall material in essential hypertensives.

We have previously shown that the decrease in large artery distensibility observed in patients with essential hypertension (HT group) was primarily due to an increase in distending pressure and not to hypertension-associated structural modifications of the artery, suggesting a functional adaptation of the wall material. To evaluate the elastic properties of the wall material of the common carotid artery, we determined Young's incremental elastic modulus (Einc) in the HT group and in normotensive subjects (NT group) as a function of blood pressure and circumferential wall stress. In 102 HT patients with never-treated essential hypertension and 40 age- and gender-matched NT subjects, the Einc-pressure and Einc-stress curves were calculated from intima-media thickness and from diameter and pressure waveforms, determined with echo tracking and aplanation tonometry, respectively. The "effective" stiffness of the wall material, determined through Einc calculated at mean blood pressure, was significantly higher in the HT than in the NT group. The "intrinsic" stiffness of the wall material, determined through Einc calculated at a common circumferential wall stress, did not differ between the 2 groups. However, when each group (HT and NT) was analyzed according to tertiles of age, the "intrinsic" stiffness of the arterial wall material was increased only in younger HT patients. In middle-aged and older HT patients, the intrinsic mechanical properties of the carotid arterial wall material were unchanged, and the increased stiffness of the common carotid artery in the HT group was due primarily to the increased level of blood pressure. These results also indicate that the deleterious effects of aging and hypertension on "intrinsic" stiffness are not additive.

Reproducibility of coronary calcification detection with electron-beam computed tomography.

If coronary calcification scores obtained with electron-beam computed tomography (EBT) were proved to be correlated to coronary atherosclerosis, the reproducibility of the technique had to be assessed before being used for patient follow-up. A total of 150 patients, selected as a result of a cholesterol screening programme, were studied by EBT. Twelve contiguous 3-mm-thick transverse slices beginning on the proximal coronary arteries were obtained through the base of the heart. The amount of calcium was evaluated as the calcified area weighted by a coefficient depending on the density peak level. The value was expressed as a logarithmic scale. Intra-observer, inter-observer and inter-examination reproducibilities were calculated. They were 1.9, 1.3 and 7.2%, respectively. These results were good enough to allow the use of EBT for longitudinal studies. The influence of acquisition and calculation conditions on score computation were also analysed.

Mechanical strength of the isolated carotid artery in SHR.

We have previously reported an adaptation of arterial wall elasticity in spontaneously hypertensive rats (SHR) that involves an increase in both fibronectin/alpha5beta1-integrin complexes and smooth-muscle elastic lamellae connections. We examined the mechanical strength (MS) of the carotid artery in relation to its elastic properties, its elastin/collagen content, and the structure of the internal elastic lamina. MS was defined as the in vitro intraluminal pressure and wall stress that produces rupture of the vascular wall. Intact carotid arteries from 3-month-old normotensive rats (Wistar-Kyoto, WKY) and SHR were cannulated on a specially designed device and adjusted to their in situ length. A slowly increasing static pressure was applied until wall rupture occurred to determine the static mechanical behavior and MS. Static elasticity was similar in SHR and WKY, as were the rupture pressure (2740+/-90 versus 2740+/-40 mm Hg) and wall stress at rupture (11.5+/-1.0 versus 12.8+/-0.4 MPa), indicating equivalent MS in both groups. Histological examination showed several wall ruptures and dissociation of lamellar units that did not differ significantly between the 2 groups. Confocal microscopy showed that the size of fenestrations of the internal elastic lamina and the fraction of area occupied by them were reduced 3-fold in SHR. We have demonstrated that static elasticity of the arterial wall and mechanical strength are similar in carotid arteries from SHR and WKY.

Effects of clonidine and flesinoxan on blood pressure variability in conscious spontaneously hypertensive rats.

The effects of two centrally acting antihypertensive agents, clonidine (0.1 mg/kg/day s.c.) and flesinoxan (1 mg/kg/day s.c.), on short-term blood pressure variability (BPV) were investigated in conscious spontaneously hypertensive rats (SHRs). The drugs were infused subcutaneously during 24 h and 4 weeks by osmotic minipumps. BPV was characterized by spectral analysis. In conscious SHRs, clonidine significantly and preferentially reduced the low frequency (LF; 0.25-0.75 Hz) oscillations of mean arterial pressure (MAP) in short-term (24 h) and long-term (4 weeks) treatments but significantly decreased MAP level only in short-term treatments. In contrast, flesinoxan significantly reduced MAP level whatever the duration of infusion but decreased LF-MAP only in short-term treatments. These results show that centrally mediated inhibition of sympathetic tone by stimulation of either alpha2-adrenoceptors or 5-HT1A (serotonin) receptors can reduce BPV. This effect is independent of the modifications in BP level. The effects of the drugs on baroreceptors may also contribute to the decrease in BPV. The dual properties of clonidine (alpha2-adrenoceptors and imidazoline receptors) may account for its differential effects on BP level and BPV.

Maximal thickness of the normal human pericardium assessed by electron-beam computed tomography.

The purpose of this study was to determine the maximal value of normal pericardial thickness with an electron-beam computed tomography unit allowing fast scan times of 100 ms to reduce cardiac motion artifacts. Electron-beam computed tomography was performed in 260 patients with hypercholesterolemia and/or hypertension, as these pathologies have no effect on pericardial thickness. The pixel size was 0.5 mm. Measurements could be performed in front of the right ventricle, the right atrioventricular groove, the right atrium, the left ventricle, and the interventricular groove. Maximal thickness of normal pericardium was defined at the 95th percentile. Inter-observer and intra-observer reproducibility studies were assessed from additional CT scans by the Bland and Altman method [24]. The maximal thickness of the normal pericardium was 2 mm for 95 % of cases. For the reproducibility studies, there was no significant relationship between the inter-observer and intra-observer measurements, but all pericardial thickness measurements were

Fibronectin expression and aortic wall elastic modulus in spontaneously hypertensive rats.

Recent studies have shown that large-artery wall remodeling per se does not reduce distensibility in hypertension, indicating qualitative or quantitative changes in arterial components. The aim of the study was to determine in 1-year-old spontaneously hypertensive rats (SHRs) the changes in the elastic properties of large arteries, as assessed by the incremental elastic modulus (E(inc)), and the changes in the extracellular matrix, including fibronectin (FN) and alpha5beta1-integrin. The relationship between E(inc) and circumferential wall stress was calculated from in vivo pulsatile changes in blood pressure and arterial diameter by using a high-resolution echo-tracking system at the site of the abdominal aorta and in vitro medial cross-sectional area. E(inc)-stress curves and FN and integrin alpha5-subunit contents were determined for each animal. Mean stress and E(inc) were higher in SHRs than in Wistar rats. However, in a common range of stress, E(inc)-stress curves for SHRs were superimposable on those for Wistar rats, indicating that wall materials in both strains have equivalent mechanical behavior. Immunohistochemistry indicated that total FN, EIIIA FN isoform, and alpha5-integrin increased in the SHRs aortas without changes in elastin and collagen densities. Total FN was also increased in SHRs as determined by Western blot analysis. No differences in FN and alpha5-subunit mRNAs were detected between SHRs and Wistar rats. These results indicate that the aortic wall material of SHRs and Wistar rats have equivalent mechanical properties, although in SHRs it is subjected to a higher level of stress. By increasing cell-matrix attachment sites, FN may participate in the mechanical adaptation of both cellular and matrix components in SHRs.

Fenestrations of the carotid internal elastic lamina and structural adaptation in stroke-prone spontaneously hypertensive rats.

Our aim was to determine the structural factors that determine the mechanical adaptation of the carotid arterial wall in stroke-prone hypertensive rats (SHRSP). Distensibility-pressure and elastic modulus-stress curves assessed by in vivo echo-tracking measurements indicated a reduction in arterial stiffness in 13-week-old SHRSP compared with Wistar-Kyoto rats (WKY). Elastin and collagen contents determined biochemically were not different between SHRSP and WKY. Confocal microscopy showed that the mean area of fenestrations and fraction of area occupied by fenestrations of the internal elastic lamina (IEL) were smaller in SHRSP than in WKY, which indicated a reduction in stress-concentration effects within the IEL. Immunohistologic staining of EIIIA fibronectin isoform and total fibronectin (also as determined by Western blot) was greater in SHRSP, which suggested increased cell-matrix interactions. We suggest that these structural modifications of the vascular wall play a synergistic role in the mechanical adaptation to a high level of stress in SHRSP.

In vivo/in vitro comparison of rat abdominal aorta wall viscosity. Influence of endothelial function.

Arterial wall viscosity (AWV) is a potential source of energy dissipation in circulation. That arteries, which are known to be markedly viscous in vitro, have lower viscosity in vivo has been suggested but not demonstrated under similar pressure conditions. Endothelium, which may modulate AWV through smooth muscle tone, could contribute to the low level of viscosity in vivo. Our objectives were first to compare AWV of the rat abdominal aorta, in vivo and in vitro, with similar pulse-pressure waves, and second, to determine whether endothelial function influences AWV in vivo and in vitro. The diameter of the abdominal aorta and distending pressure were measured in vivo and in vitro with a high-resolution echotracking system and a micromanometer, respectively. AWV was calculated as the area of the pressure-volume curve hysteresis. After in vivo examination, the arterial segments were isolated in vitro and submitted to resynthesized pressure waves identical to those recorded in vivo. Deendothelialization was performed in vivo by balloon rubbing; then arteries were examined either in vivo or in vitro. AWV was markedly lower in vivo than in vitro (6.6 +/- 0.7 versus 22.7 +/- 3.7 J.m-1.10(-5), respectively; P < .001). After deendothelialization, a sustained 40% increased AWV was observed during a 15-minute follow-up (P < .01). In vitro, deendothelialized arteries have a 64% higher AWV than segments with endothelium (P < .01). Our results indicate that the physiological effective viscosity, measured in vivo in intact animals, is threefold lower than the intrinsic viscosity of the arterial wall, measured in vitro. Endothelium removal determines a sustained increase in AWV, either in vivo or in vitro. These results suggest that active mechanisms compensate for intrinsic viscosity under physiological conditions. One of these energy-saving mechanisms might be dependent on normal endothelial function.

Structural changes and in situ aortic pressure-diameter relationship in long-term chemical-sympathectomized rats.

This study determined the effects of long-term chemical sympathectomy with guanethidine (GN) on the mechanical properties and composition of the distal abdominal aorta in Wistar rats. GN was daily administered for 3 mo (3M-GN, from 1 to 12 wk), 5 wk (5W-GN, from 7 to 12 wk), and 8 days (8D-GN, from 11 to 12 wk). All experiments were performed at 12 wk of age to avoid age differences at examination. We used a high-resolution echo-tracking system to determine in situ, in the systolic-diastolic range, the aortic diameter-, compliance-, and distensibility-pressure curves in anesthetized rats. We observed an equivalent significant fall in the tyramine pressor response in all conscious GN-treated rats. Blood pressure was not affected by sympathectomy after 8 days and 5 wk of treatment but was significantly reduced in 3M-GN rats. Chronic sympathetic denervation increased aortic diameter and compliance in 8D-GN rats, compared with those obtained at the same distending pressure in control rats, suggesting vascular smooth muscle relaxation. In contrast, in 5W-GN and 3M-GN rats, the distensibility pressure-curves were significantly shifted toward lower levels of distensibility and pressure, indicating a decreased aortic distensibility at the same level of arterial pressure. Sympathectomy produced a significant reduction in the content of elastin, one of the most distensible components of the arterial wall in 5W-GN and 3M-GN rats. These results suggest that intact sympathetic nerves are necessary to maintain normal functional and structural properties of large arteries in rat. The reduction in aortic distensibility, in long-term sympathectomized rats, could have resulted from complex interactions between local aortic denervation, change in the set point of distending pressure, and changes in aortic smooth muscle tone and/or wall composition.