Multiphoton microscopy observations of 3D elastin and collagen fiber microstructure changes during pressurization in aortic media

Elastin and collagen fibers play important roles in the mechanical properties of aortic media. Because knowledge of local fiber structures is required for detailed analysis of blood vessel wall mechanics, we investigated 3D microstructures of elastin and collagen fibers in thoracic aortas and monitored changes during pressurization. Using multiphoton microscopy, autofluorescence images from elastin and second harmonic generation signals from collagen were acquired in media from rabbit thoracic aortas that were stretched biaxially to restore physiological dimensions. Both elastin and collagen fibers were observed in all longitudinal–circumferential plane images, whereas alternate bright and dark layers were observed along the radial direction and were recognized as elastic laminas (ELs) and smooth muscle-rich layers (SMLs), respectively. Elastin and collagen fibers are mainly oriented in the circumferential direction, and waviness of collagen fibers was significantly higher than that of elastin fibers. Collagen fibers were more undulated in longitudinal than in radial direction, whereas undulation of elastin fibers was equibiaxial. Changes in waviness of collagen fibers during pressurization were then evaluated using 2-dimensional fast Fourier transform in mouse aortas, and indices of waviness of collagen fibers decreased with increases in intraluminal pressure. These indices also showed that collagen fibers in SMLs became straight at lower intraluminal pressures than those in EL, indicating that SMLs stretched more than ELs. These results indicate that deformation of the aorta due to pressurization is complicated because of the heterogeneity of tissue layers and differences in elastic properties of ELs, SMLs, and surrounding collagen and elastin.     

Improving smooth muscle cell exposure to drugs from drug-eluting stents at early time points: a variable compression approach

The emergence of drug-eluting stents (DES) as a viable replacement for bare metal stenting has led to a significant decrease in the incidence of clinical restenosis. This is due to the transport of anti-restenotic drugs from within the polymer coating of a DES into the artery wall which arrests the cell cycle before restenosis can occur. The efficacy of DES is still under close scrutiny in the medical field as many issues regarding the effectiveness of DES drug transport in vivo still exist. One such issue, that has received less attention, is the limiting effect that stent strut compression has on the transport of drug species in the artery wall. Once the artery wall is compressed, the stents ability to transfer drug species into the arterial wall can be reduced. This leads to a reduction in the spatial therapeutic transfer of drug species to binding sites within the arterial wall. This paper investigates the concept of idealised variable compression as a means of demonstrating how such a stent design approach could improve the spatial delivery of drug species in the arterial wall. The study focused on assessing how the trends in concentration levels changed as a result of artery wall compression. Five idealised stent designs were created with a combination of thick struts that provide the necessary compression to restore luminal patency and thin uncompressive struts that improve the transport of drugs therein. By conducting numerical simulations of diffusive mass transport, this study found that the use of uncompressive struts results in a more uniform spatial distribution of drug species in the arterial wall.     

Modelling intravascular delivery from drug-eluting stents with biodurable coating: investigation of anisotropic vascular drug diffusivity and arterial drug distribution

In-stent restenosis occurs in coronary arteries after implantation of drug-eluting stents with non-uniform restenosis thickness distribution in the artery cross section. Knowledge of the spatio-temporal drug uptake in the arterial wall is useful for investigating restenosis growth but may often be very expensive/difficult to acquire experimentally. In this study, local delivery of a hydrophobic drug from a drug-eluting stent implanted in a coronary artery is mathematically modelled to investigate the drug release and spatio-temporal drug distribution in the arterial wall. The model integrates drug diffusion in the coating and drug diffusion with reversible binding in the arterial wall. The model is solved by the finite volume method for both high and low drug loadings relative to its solubility in the stent coating with varied isotropic–anisotropic vascular drug diffusivities. Drug release profiles in the coating are observed to depend not only on the coating drug diffusivity but also on the properties of the surrounding arterial wall. Time dependencies of the spatially averaged free- and bound-drug levels in the arterial wall on the coating and vascular drug diffusivities are discussed. Anisotropic vascular drug diffusivities result in slightly different average drug levels in the arterial wall but with very different spatial distributions. Higher circumferential vascular diffusivity results in more uniform drug loading in the upper layers and is potentially beneficial in reducing in-stent restenosis. An analytical expression is derived which can be used to determine regions in the arterial with higher free-drug concentration than bound-drug concentration.     

Synchrotron radiation X-ray fluorescence microscopy reveals a spatial association of copper on elastic laminae in rat aortic media

Copper, an essential trace metal in humans, plays an important role in elastic formation. However, little is known about the spatial association between copper, elastin, and elastin producing cells. The aorta is the largest artery; the aortic media is primarily composed of the elastic lamellae and vascular smooth muscle cells, which makes it a good model to address this issue. Synchrotron radiation X-ray fluorescence microscopy (SRXRF) is a new generation technique to investigate the spatial topography of trace metals in biological samples. Recently, we utilized this technique to determine the topography of copper as well as other trace elements in aortic media of Sprague Dawley rats. A standard rat diet was used to feed Sprague Dawley rats, which contains the normal dietary requirements of copper and zinc. Paraffin embedded segments (4 μm of thickness) of thoracic aorta were analyzed using a 10 keV incident monochromatic X-ray beam focusing on a spot size of 0.3 μm × 0.2 μm (horizontal × vertical). The X-ray spectrum was measured using an energy-dispersive silicon drift detector for elemental topography. Our results showed that phosphorus, sulfur, and zinc are predominately distributed in the vascular smooth muscle cells, whereas copper is dramatically accumulated in elastic laminae, indicating a preferential spatial association of copper on elastic laminae in aortic media. This finding sheds new light on the role of copper in elastic formation. Our studies also demonstrate that SRXRF allows for the visualization of trace elements in tissues and cells of rodent aorta with high spatial resolution and provides an opportunity to study the role of trace elements in vasculature.     

A biophysical and histological analysis of factors that lead to aortic rupture in normal and lathyritic turkeys

These experiments were designed to determine if local differences in elastic properties or wall structure contributed to the development of aortic rupture in turkeys. Static elastic properties were measured from pressure-volume curves of cylindrical segments of upper and lower thoracic aorta and innominate artery in two groups of lathyritic birds and two age-matched control groups. The biggest changes were in the young lathyritic group that was on 0.04% beta-aminoproprionitrile at 3 weeks of age and continued for 2, 3, or 4 weeks. Much smaller changes were seen in the older group that started on 0.05% beta-aminoproprionitrile at 6 weeks of age for 10 days and then 0.02% beta-aminoproprionitrile for the next 9-12 weeks. The biggest changes were seen in the abdominal aorta, which ruptured spontaneously in 50% of the young lathyritic group. The birds had a marked decrease in the number of elastin layers per unit wall thickness. Analysis of the elastic diagrams showed that the elastance of both elastin and collagen were altered in the young lathyritic group. Rupture appeared to follow partial dissection of plaques, but true longitudinal dissection did not occur.     

Intramural delivery of Sirolimus prevents vascular remodeling following balloon injury

OBJECTIVE: Several studies have demonstrated that Sirolimus-eluting stents reduce restenosis in patients with coronary artery disease. Here, we tested whether direct delivery of Sirolimus into the vessel wall during balloon angioplasty can modify vascular remodeling over several weeks. METHODS AND RESULTS: During angioplasty of the rabbit iliac artery we administered an intramural infusion of Sirolimus or its vehicle directly through a balloon catheter into the vessel wall. After 3 weeks neointimal formation was decreased (0.71+/-0.1 vs. 1.4+/-0.12 intima/media ratio), and this process was attributed to the inhibitory properties of Sirolimus on ECM deposition and smooth muscle cell proliferation. Sirolimus also significantly reduced the deposition of elastin, collagen III and fibronectin within the vascular wall. In parallel, proteomic profiles of arterial wall segments were obtained and 485 protein spots were consistently matched between non-dilated and dilated vessels. Differential expression of 12 proteins were observed between the groups and direct sequencing of digested peptides was performed. Local delivery of sirolimus during angioplasty attenuated the expression of structural proteins that included lamin A, vimentin, alpha-1-antitrypsin, and alpha-actin. CONCLUSIONS: Local administration of Sirolimus during angioplasty prevents smooth muscle cell proliferation associated with vascular remodeling as well as the expression of extracellular matrix and structural proteins. Therefore, local injection of Sirolimus during balloon inflation may be an alternative therapeutic approach for preventing restenosis in small stenotic vessels (i.e., <2.5 mm).     

慢性阻断血管紧张素Ⅱ1型受体不能完全防止模拟失重大鼠血管的适应性结构变化

我们以前的工作提示,在模拟失重所引起的血管区域特异性适应变化中,局部肾素．血管紧张素系统（local reninangiotensin system,L-RAS）可能发挥关键调控作用。本文以losartan慢性阻断血管紧张素Ⅱ1型受体（angiotensin Ⅱtypelreceptor,AT1R）,观察模拟失重是否仍能引起血管的这种适应性改变,并检测大血管管壁L-RAS主要成分的表达是否也发生相应变化。以尾部悬吊大鼠模型模拟失重的生理影响。制作基底动脉、胫前动脉、颈总动脉和腹主动脉的HE染色切片,在光学显微镜下进行形态观测：用免疫组织化学技米测量颈总动脉和腹主动脉壁的血管紧张素原（angiotensinogen,AGT）及AT-R的表达变化。结果表明：4周模拟失重引起大鼠基底动脉中膜和颈总动脉管壁各平滑肌肌层肥厚,而胫前动脉和腹主动脉则发生萎缩性改变;给予losartan4周引起上述4种血管皆发生萎缩性变化;阻断AT1R,模拟失重仍然能引起基底动脉、颈总动脉发生相对肥厚性改变和腹主动脉萎缩加重。4周模拟失重还引起颈总动脉壁中AGT和AT1R表达上调,而腹主动脉壁及血管周围组织中AGT和AT1R表达下调;给予losartan4周仅引起腹主动脉壁中AGT和AT1R表达减少;阻断AT1R,模拟失重使腹主动脉壁AT1R表达进一步减少。结果提示,4周模拟失重引起大鼠脑、颈部与后身大、中动脉血管的形态结构改变和L-RAS主要成分表达发生上调或下调,血管L-RAS在其中可能发挥关键性调控作用;但在慢性阻断AT1R的条件下,其它调控机制仍可能在脑血管适应性调节中发挥一定作用。     

Electron microscopic observations of elastic fibres in the lung and aorta of tight-skin and beta-aminopropionitrile-fed mice.

The lung of the tight-skin (TSK) mouse was characterized by enlargement of the air spaces. Elastin in the alveolar walls of the TSK mouse exhibited fragmentation. The aorta of the TSK mouse was characterized by marked hyperplasia of loose connective tissue in the adventitia. Collagen fibres and ruthenium red-positive materials were markedly increased. Microfibrils surrounding elastin in the adventitia of the aorta were not clear in the TSK mouse. In the lung of the beta-aminopropionitrile (BAPN)-fed mouse, enlargement of the alveolar air spaces was not prominent compared with the TSK mouse. Elastic fibres in the alveolar walls did not show the fragmentation observed in the TSK mouse, and microfibrils surrounding elastin were clearly observed. However, elastic laminae in the media of the BAPN-fed mouse aorta were swollen and fragmented. Elastic fibres in the adventitia exhibited a normal appearance and microfibrils surrounding elastin in the adventitia were clearly observed. The results suggest that the mechanism of the connective tissue abnormality in the TSK mouse is different from that of BAPN, which inhibits the activity of lysyl oxidase. The abnormality of elastin and microfibrils surrounding elastin in the TSK mouse probably plays a role in the deformity or degradation of elastic fibres and the structural changes of the lung.     

Hyperhomocysteinemia induces elastolysis in minipig arteries: Structural consequences, arterial site specificity and effect of captopril-hydrochlorothiazide

Hyperhomocysteinemia is a risk factor for arterial diseases, and the deterioration of the arterial elastic structures is one of the possible mechanisms underlying this epidemiological association. The aim of this paper is to quantitively characterize such structural alterations and to explore their causes in a previous model of dietary induced mild hyperhomocysteinemia in minipigs. After four months, both a morphodensitometrical analysis of the elastic structure and a biochemical analysis of elastin and elastase activities were performed on the infrarenal abdominal aorta (IRAA) and the proximal left interventricular coronary artery (LIVCA) of control (C), hyperhomocysteinemic (H) and captopril-hydrochlorothiazide (Cp-Htz, 25 + 12.5 mg/d)-treated (H+Cp) minipigs (n = 8/group).Hyperhomocysteinemia was found to induce an increase in parietal elastolytic metalloproteinase activities. It resulted in opening and enlargement of fenestrae through the medial elastic laminae and in a decrease in medial elastin content (p < 10⁻³), expressed as well as volume density (%) as weight concentration (μg elastin/mg dry tissue). The thickness of the media and its basic lamellar organization was unchanged. The reduction in volume density was more dramatic in LIVCA (H: 4.7 ± 0.9 vs C: 8.8 ±2.4), where it was evenly distributed within media, than in IRAA (H: 6.7 ± 1.1 vs C: 9.3± 1.2), where the deep media layers were less affected. Cp-Htz partly prevented the hyperhomocysteinemia-induced reduction of the medial elastin content LIVCA (5.7 ± 1.2) and IRAA (7.9 ± 1.4). This effect, occurring in the subintimal layers of the media in both arteries but not in the deeper layers, resulted in a less beneficial effect in LIVCA than in IRAA. This result parallels the moderate beneficial therapeutic effect of ACE inhibitors against coronary atherosclerosis in humans.     

Crosslinked elastic fibers are necessary for low energy loss in the ascending aorta

In the large arteries, it is believed that elastin provides the resistance to stretch at low pressure, while collagen provides the resistance to stretch at high pressure. It is also thought that elastin is responsible for the low energy loss observed with cyclic loading. These tenets are supported through experiments that alter component amounts through protease digestion, vessel remodeling, normal growth, or in different artery types. Genetic engineering provides the opportunity to revisit these tenets through the loss of expression of specific wall components. We used newborn mice lacking elastin (Eln^−/−) or two key proteins (lysyl oxidase, Lox^−/−, or fibulin-4, Fbln4^−/−) that are necessary for the assembly of mechanically-functional elastic fibers to investigate the contributions of elastic fibers to large artery mechanics. We determined component content and organization and quantified the nonlinear and viscoelastic mechanical behavior of Eln^−/−, Lox^−/−, and Fbln4^−/− ascending aorta and their respective controls. We confirmed that the lack of elastin, fibulin-4, or lysyl oxidase leads to absent or highly fragmented elastic fibers in the aortic wall and a 56–97% decrease in crosslinked elastin amounts. We found that the resistance to stretch at low pressure is decreased only in Eln^−/− aorta, confirming the role of elastin in the nonlinear mechanical behavior of the aortic wall. Dissipated energy with cyclic loading and unloading is increased 53–387% in Eln^−/−, Lox^−/−, and Fbln4^−/− aorta, indicating that not only elastin, but properly assembled and crosslinked elastic fibers, are necessary for low energy loss in the aorta.     

A theory for water and macromolecular transport in the pulmonary artery wall with a detailed comparison to the aorta

The pulmonary artery (PA) wall, which has much higher hydraulic conductivity and albumin void space and approximately one-sixth the normal transmural pressure of systemic arteries (e.g, aorta, carotid arteries), is rarely atherosclerotic, except under pulmonary hypertension. This study constructs a detailed, two-dimensional, wall-structure-based filtration and macromolecular transport model for the PA to investigate differences in prelesion transport processes between the disease-susceptible aorta and the relatively resistant PA. The PA and aorta models are similar in wall structure, but very different in parameter values, many of which have been measured (and therefore modified) since the original aorta model of Huang et al. (23). Both PA and aortic model simulations fit experimental data on transwall LDL concentration profiles and on the growth of isolated endothelial (horseradish peroxidase) tracer spots with circulation time very well. They reveal that lipid entering the aorta attains a much higher intima than media concentration but distributes better between these regions in the PA than aorta and that tracer in both regions contributes to observed tracer spots. Solutions show why both the overall transmural water flow and spot growth rates are similar in these vessels despite very different material transport parameters. Since early lipid accumulation occurs in the subendothelial intima and since (matrix binding) reaction kinetics depend on reactant concentrations, the lower intima lipid concentrations in the PA vs. aorta likely lead to slower accumulation of bound lipid in the PA. These findings may be relevant to understanding the different atherosusceptibilities of these vessels.     

Compromised mechanical homeostasis in arterial aging and associated cardiovascular consequences

Aging leads to central artery stiffening and associated hemodynamic sequelae. Because healthy arteries exhibit differential geometry, composition, and mechanical behaviors along the central vasculature, we sought to determine whether wall structure and mechanical function differ across five vascular regions—the ascending and descending thoracic aorta, suprarenal and infrarenal abdominal aorta, and common carotid artery—in 20 versus 100-week-old male wild-type mice. Notwithstanding generally consistent changes across these regions, including a marked thickening of the arterial wall, diminished in vivo axial stretch, and loss of elastic energy storage capacity, the degree of changes tended to be slightly greater in abdominal than in thoracic or carotid vessels. Likely due to the long half-life of vascular elastin, most mechanical changes in the arterial wall resulted largely from a distributed increase in collagen, including thicker fibers in the media, and localized increases in glycosaminoglycans. Changes within the central arteries associated with significant increases in central pulse pressure and adverse changes in the left ventricle, including increased cardiac mass and decreased diastolic function. Given the similar half-life of vascular elastin in mice and humans but very different life-spans, there are important differences in the aging of central vessels across these species. Nevertheless, the common finding of aberrant matrix remodeling contributing to a compromised mechanical homeostasis suggests that studies of central artery aging in the mouse can provide insight into mechanisms and treatment strategies for the many adverse effects of vascular aging in humans.     

Linked mechanical and biological aspects of remodeling in mouse pulmonary arteries with hypoxia-induced hypertension

Supravalvular aortic stenosis (SVAS) is associated with decreased elastin and altered arterial mechanics. Mice with a single deletion in the elastin gene (ELN(+/-)) are models for SVAS. Previous studies have shown that elastin haploinsufficiency in these mice causes hypertension, decreased arterial compliance, and changes in arterial wall structure. Despite these differences, ELN(+/-) mice have a normal life span, suggesting that the arteries remodel and adapt to the decreased amount of elastin. To test this hypothesis, we performed in vitro mechanical tests on abdominal aorta, ascending aorta, and left common carotid artery from ELN(+/-) and wild-type (C57BL/6J) mice. We compared the circumferential and longitudinal stress-stretch relationships and residual strains. The circumferential stress-stretch relationship is similar between genotypes and changes <3% with longitudinal stretch at lengths within 10% of the in vivo value. At mean arterial pressure, the circumferential stress in the ascending aorta is higher in ELN(+/-) than in wild type. Although arterial pressures are higher, the increased number of elastic lamellae in ELN(+/-) arteries results in similar tension/lamellae compared with wild type. The longitudinal stress-stretch relationship is similar between genotypes for most arteries. Compared with wild type, the in vivo longitudinal stretch is lower in ELN(+/-) abdominal and carotid arteries and the circumferential residual strain is higher in ELN(+/-) ascending aorta. The increased circumferential residual strain brings the transmural strain distribution in ELN(+/-) ascending aorta close to wild-type values. The mechanical behavior of ELN(+/-) arteries is likely due to the reduced elastin content combined with adaptive remodeling during vascular development.     

Localization of elastin mRNA and TGF-β1 in rat aorta and caudal artery as a function of age

Several in vitro studies have previously demonstrated that the addition of TGF-β to aortic smooth muscle cells or skin fibroblasts stimulates elastin synthesis. It is not clear however whether, in vivo, TGF-β participates in the regulation of elastin synthesis, especially in physiological conditions. The aim of our study was to explore the localization of elastin mRNA and TGF-β1 in the rat thoracic aorta (an elastic artery) and caudal artery (a muscular artery). Elastin mRNA was localized by in situ hybridization and quantified using Northern blot analysis. TGF-β1 was detected using immunohistochemistry. The study was carried out as a function of age (rats of 3, 10, 20, and 30 months). We observed that TGF-β1 immunoreactivity is present predominantly, but not exclusively, at the sites of elastin synthesis as determined by elastin mRNA detection: in smooth muscle cells in the aorta and in endothelial cells in the caudal artery. The ability of exogenously added TGF-β1 (0.001–10 ng/ml) to modulate the steady-state levels of elastin mRNA in primary cultures of endothelial cells, smooth muscle cells, and fibroblasts isolated from the thoracic aorta was also studied. At the highest concentration used, elastin mRNA levels increased 5-fold in endothelial cells and 11-fold in smooth muscle cells. The demonstration that TGF-β1 immunoreactivity is present at the sites of elastin synthesis in the thoracic aorta and in the caudal artery and the observation that TGF-β1 induces an increase in elastin mRNA levels in cultured endothelial cells and smooth muscle cells suggest that TGF-β1 may be implicated, at least in part, in the physiological regulation of elastin gene expression.     

Fluid-structure Interaction within a Layered Aortic Arch Model

The response of wall stress to the elasticity of each layer in the aorta wall was investigated to understand the role of the different elastic properties of layers in the aortic dissection. The complex mechanical interaction between blood flow and wall dynamics in a three-dimensional arch model of an aorta was studied by means of computational coupled fluid-structure interaction analysis. The results show that stresses in the media layer are highest in three layers and that shear stress is concentrated in the media layer near to the adventitia layer. Hence, the difference in the elastic properties of the layers could be responsible for the pathological state in which a tear splits across the tunica media to near to the tunica adventitia and the dissection spreads along the laminar planes of the media layer where it is near the adventitia layer.     

Remodeling of Aorta Extracellular Matrix as a Result of Transient High Oxygen Exposure in Newborn Rats: Implication for Arterial Rigidity and Hypertension Risk

Neonatal high-oxygen exposure leads to elevated blood pressure, microvascular rarefaction, vascular dysfunction and arterial (aorta) rigidity in adult rats. Whether structural changes are present in the matrix of aorta wall is unknown. Considering that elastin synthesis peaks in late fetal life in humans, and early postnatal life in rodents, we postulated that transient neonatal high-oxygen exposure can trigger premature vascular remodelling. Sprague Dawley rat pups were exposed from days 3 to 10 after birth to 80% oxygen (vs. room air control) and were studied at 4 weeks. Blood pressure and vasomotor response of the aorta to angiotensin II and to the acetylcholine analogue carbachol were not different between groups. Vascular superoxide anion production was similar between groups. There was no difference between groups in aortic cross sectional area, smooth muscle cell number or media/lumen ratio. In oxygen-exposed rats, aorta elastin/collagen content ratio was significantly decreased, the expression of elastinolytic cathepsin S was increased whereas collagenolytic cathepsin K was decreased. By immunofluorescence we observed an increase in MMP-2 and TIMP-1 staining in aortas of oxygen-exposed rats whereas TIMP-2 staining was reduced, indicating a shift in the balance towards degradation of the extra-cellular matrix and increased deposition of collagen. There was no significant difference in MMP-2 activity between groups as determined by gelatin zymography. Overall, these findings indicate that transient neonatal high oxygen exposure leads to vascular wall alterations (decreased elastin/collagen ratio and a shift in the balance towards increased deposition of collagen) which are associated with increased rigidity. Importantly, these changes are present prior to the elevation of blood pressure and vascular dysfunction in this model, and may therefore be contributory.     

The canine tail artery as a model for cerebral aneurysm studies

The occluded canine tail artery, which comes off in the same plane as the aortoiliac junction, has been used as a flow model for cerebral aneurysms. These experiments were designed to determine if it is a realistic distensible model of human intracranial aneurysms. Distensibility studies were done on the aorta, and the iliac and tail arteries of four dogs. From these pressure-volume studies, tension-strain curves, elastances, and collagen slack were obtained. The tail artery is stiffer longitudinally and more distensible circumferentially than the other vessels. The iliac arteries and the aorta are not significantly different. The elastance of elastin and collagen is lower in the tail artery, and the collagen is more wavy circumferentially. Longitudinally, the collagen slack is least for the tail artery, and the elastance of elastin is not different in all three vessels. The number of elastin layers in the iliac and tail arteries seen in cross section is not significantly different, but the aorta is different from both these vessels. In another four dogs the aorta proximal to the trifurcation was cannulated and infused with saline to increase pressure. India ink marks were put on the surface to measure changes in length. Photographs were taken at intervals of 10 mmHg(1 mmHg = 133.3 Pa). This was done with the vessels tethered and untethered in the body and then taken out and studied with the same method in vitro. Arteries tethered in the body expanded circumferentially more than longitudinally. The tail artery becomes less distensible if untethered in the body and therefore acts more like an aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)     

Geometrical,functional, and histomorphometric adaptation of rat carotid artery in induced hypertension

Acute and long-term (up to 56 days) evolution of geometry, structural properties, vascular smooth muscle (VSM) tone and histomorphometric properties of the rat common carotid arteries under induced hypertension were investigated. Hypertension was induced in 8-week old male Wistar rats by total ligation of the aorta between the two kidneys. Rats were sacrificed 2, 4, 8 and 56 days postsurgery. The arterial wall layers thicken non-uniformly during the adaptation process, the inner layers thicken more in the acute phase of hypertension, whereas the outer layers of the wall are thicker than the inner layers at the end of the adaptation phase. Collagen content in the wall media exhibits a non-linear evolution, with a rapid increase in the acute hypertension phase followed by a slower increase at long-term. The elastin content increase is slight and steady, whereas VSM shows a steady but considerable increase which outdoes the collagen increase in long-term phase. VSM tone increases rapidly in the acute phase of remodelling (0-8 days) and this increase in tone contributes to a considerable increase in arterial compliance in the operating pressure range. At long-term (56 days) VSM tone returns to near control level, but compliance is even further increased, which suggests that at long-term the compliance increase is attributed primarily to structural remodelling.