Age-related changes in the contractile and passive arterial properties of murine mesenteric small arteries are altered by caveolin-1 knockout

Caveolin-1, an integral protein of caveolae, is associated with multiple cardiovascular signalling pathways. Caveolin-1 knockout (KO) mice have a reduced lifespan. As changes in artery structure and function are associated with ageing we have investigated the role of caveolin-1 ablation on age-related changes of small artery contractility and passive mechanical properties. Mesenteric small arteries isolated from 3 and 12-month wild-type (WT) and caveolin-1 KO mice were mounted on a pressure myograph and changes in passive and functional arterial properties were continuously monitored. In WT mice ageing was associated with a reduction in arterial contractility to noradrenaline which was reversed by inhibition of nitric oxide synthase with L-NNA. Similarly, in 3-month-old mice, caveolin-1 KO reduced contractility to noradrenaline by an L-NNA-sensitive mechanism. However, ageing in caveolin-1 KO mice was not associated with any further change in contractility. In WT mice ageing was associated with an increased passive arterial diameter and cross-sectional area (CSA), consistent with outward remodelling of the arterial wall, and a reduced arterial distensibility. Caveolin-1 ablation at 3 months of age resulted in similar changes in passive arterial properties to those observed with ageing in WT animals. However, ageing in caveolin-1 KO mice resulted in a reduced arterial CSA indicating different effects on passive structural characteristics from that observed in WT mice. Thus, caveolin-1 mice show abnormalities of small mesenteric artery function and passive mechanical characteristics indicative of premature vascular ageing. Moreover, caveolin-1 ablation modulates the age-related changes usually observed in mesenteric arteries of WT mice.     

Gender differences in biomechanical properties of intramural coronary resistance arteries of rats, an in vitro microarteriographic study

The prevalence of ischemic heart disease is lower in premenopausal females than in males of corresponding age. This should be related to gender differences in coronary functions. We tested whether biomechanical differences exist between intramural coronary resistance arteries of male and female rats. Intramural branches of the left anterior descending coronary artery (uniformly approximately 200microm in diameter) were isolated, cannulated and studied by microarteriography. Intraluminal pressure was increased from 2 to 90mmHg in steps and steady-state diameters were measured. Measurements were repeated in the presence of vasoconstrictor U46619 (10(-6)M) and the endothelial coronary vasodilator bradykinin (BK) (10(-6)M). Finally, passive diameters were recorded in calcium-free saline. A similar inner radius and a higher wall thickness (41.5+/-2.9microm vs. 31.4+/-2.7microm at 50mmHg in the passive condition, p<0.05) resulted in lower tangential wall stresses in male rats (18.9+/-1.9kPa vs. 24.9+/-2.5kPa at 50mmHg, p<0.05). Isobaric elastic modulus of vessels from male animals was significantly smaller at higher pressures. Vasoconstrictor response was significantly stronger in male than in female animals. Endothelial relaxations induced by BK were not different. This is the first demonstration that biomechanical characteristics of intramural coronary resistance arteries of a mammalian species are different in the male and female sexes. Higher wall thickness and higher vascular contractility in males are associated with similar endothelial function and larger high-pressure elasticity compared to females. These gender differences in biomechanics of coronary resistance arteries of rats may contribute to our better understanding the characteristic physiological and pathological differences in humans.     

Age and flow-mediated dilation: a comparison of dilatory responsiveness in the brachial and popliteal arteries

Previous investigations of age-associated changes in flow-mediated vasodilation (FMD) in women have been limited to the upper extremity and have not accounted for possible age differences in the stimulus for dilation. The purpose of the present study was to compare age differences in brachial and popliteal FMD and its stimulus (changes in shear rate following occlusion). Ultrasound-derived diameters and Doppler flow velocities of the brachial and popliteal arteries were measured in 14 young (20- to 30-yr-old) and 14 older (60- to 79-yr-old) healthy women at rest and during and after 5 min of distal cuff occlusion. Resting diameters were similar (both P > 0.39) in both age groups. Peak shear rate did not differ with age in either artery: approximately 1,300-1,400 and approximately 400-500 s(-1) in brachial and popliteal arteries, respectively. FMD (percent change above diameter measured during occlusion) was approximately 50-60% lower (P < 0.05) in the brachial (15.8 + 0.8% vs. 8.1 + 1.5%) and popliteal (4.6 +/- 0.7% vs. 1.8 +/- 0.4%) arteries of the older women. The normalized response of the brachial and popliteal arteries (%FMD per unit change in shear rate) was also reduced with age (55% and 53%, respectively) but did not exhibit limb specificity. Additionally, endothelium-independent dilation, as assessed by administration of nitroglycerin, was similarly blunted (by 45-65%) in brachial and popliteal arteries of older women. These results suggest that 1) brachial and popliteal artery FMD (after 5 min of distal occlusion) are similarly reduced with age, 2) when normalized to the change in shear stimulus, both arteries are equally responsive to 5 min of distal cuff occlusion in women, and 3) the age-associated decline in FMD may be attributable in part to diminished smooth muscle responsiveness.     

WISE 2005: flow and nitroglycerin mediated dilation following 56 days of head down tilt bed rest with and without an exercise countermeasure

This investigation set out to determine the effect of 56 days of head-down tilt bed rest (HDBR) and an exercise countermeasure on endothelial dependent and independent vascular function. 24women took part in this study. 8 subjects completed lower body resistance and aerobic exercise (EX, treadmill running 3-4 days per week for 40-min followed by 10-min of static LBNP, and resistive exercise on a flywheel device every 3rd day) and 16 subjects were considered as non-exercisers in a control group and a protein supplement group. FMD was induced by release of distal limb ischemia and NMD by sublingual administration of 0.3 mg of nitroglycerin before and after HDBR. Preliminary results of this study suggest that HDBR without EX results in a decreased resting diameter of the popliteal while EX increased the diameter. It is also suggested that FMD was elevated without exercise in both brachial and popliteal arteries, while pre-HDBR FMD was preserved by EX in the popliteal, but not the brachial artery. NMD appears to be elevated in the popliteal and femoral in the absence of exercise, but unchanged in the brachial artery or at any site for EX.     

Early calcification patterns of the iliac arteries and their relation to the arterial structure

Summary Gross calcifications of the common iliac and internal iliac arteries represent a common finding in newborn children and infants. In both arteries, the calcific deposits regularly appear in certain areas of the arterial luminal surface only, whereas the other parts of the arterial wall remain free of gross lesions even in cases with a pronounced calcification. In the common iliac artery, the lateral wall of the vessel and the adjacent sectors of the anterior and posterior wall represent the predilection site of calcific deposits. In the internal iliac artery, the gross calcifications have been regularly demonstrated in the dorso-medial wall. The predominant localisation of the calcification in these parts of the vessels and its absence in the others depend on the definite structural features of the arterial tube and different affinity for calcium of the individual structural elements. In both iliac arteries, only the primary internal elastic membrane undergoes early calcification. However, unlike the most muscular arteries, this membrane is not developed in the whole arterial circumference of the common iliac and internal iliac arteries, but is absent in large areas of their arterial luminal layer. In these areas, the subendothelial or subintimal elastic layers are formed by the networks of longitudinally arranged elastic fibers or membraneous elastic structures which arise from the elastic networks with the further growth. These elastic elements always stay free of calcific deposits. The structural features found in both iliac arteries may be important for the development of the later pathological changes.     

Shear level influences resistance artery remodeling: wall dimensions, cell density, and eNOS expression

The magnitude of shear stimulus has been shown to determine the level of growth factor expression in cell culture. However, little is known regarding what effect shear level has on specific arterial wall remodeling events in vivo. We have hypothesized that the rate of luminal diameter change and specific remodeling events within the arterial wall layers are dependent on shear level. Selective ligations were made to alter the number of microvascular perfusion units of mesenteric arteries within the same animal to approximately 50%, 200%, and 400% of control. Arterial blood flow and wall shear rate were correlated with the degree of alteration in perfusion units. Luminal diameters were decreased in 50% arteries by day 2 and increased approximately 17% and 33% respectively, in 200% and 400% arteries at day 7. The rate of diameter change was greatest in 50% and 400% arteries. Wall areas (medial +37%; intimal +18% at day 2) and cell densities (intimal +26%; adventitial +44% at day 2) were altered only in the 400% arteries. A positive correlation existed by day 2 between endothelial staining for endothelial nitric oxide synthase and shear level. The results demonstrate that shear level influences the rate of luminal expansion, specific remodeling events within each wall layer, and the degree of endothelial gene expression. A greater understanding of how shear level influences specific remodeling events within each wall layer should aid in the development of targeted therapies to manipulate the remodeling process in health and disease.     

Toward functional genomics of flow-induced outward remodeling of resistance arteries

In resistance-sized arteries, a chronic increase in blood flow leads to increases in arterial structural luminal diameter and arterial wall mass. In this review, we summarize recent evidence that outward remodeling of resistance arteries 1) can help maintain and restore tissue perfusion, 2) is not intimately related to flow-induced vasodilatation, 3) involves transient dedifferentiation and turnover of arterial smooth muscle cells, and 4) is preceded by increased expression of matricellular proteins, which have been shown to promote disassembly of focal adhesion sites. Studies of experimental and physiological resistance artery remodeling involving differential gene expression analyses and the use of knockout and transgenic mouse models can help unravel the mechanisms of outward remodeling.     

Interaction of 4-hydroxylated estradiol and potential-sensitive Ca2+ channels in altering uterine blood flow during the estrous cycle and early pregnancy in gilts

This study was conducted to define further the role of catechol estrogens (CE) as intermediates in estrogen-stimulated uterine hyperemia. Previous studies from our laboratory strongly suggest that changes in uterine blood flow (UBF) result from alterations in uterine arterial tone (distensibility) and/or contractility (reactivity to alpha 1-adrenergic agonists). Tone changes appear to set the baseline rate of flow, whereas contractility changes result in short-term reductions in luminal diameter. Changes in uterine arterial tone and contractility result from alterations in Ca2+ uptake through potential-sensitive channels (PSCs) and receptor-operated channels (ROCs), respectively. Uterine and mesenteric arteries were removed from 6 gilts at estrus (Day 0), 9 gilts on Day 13 of gestation (high estrogen, high UBF), and 8 gilts on Day 13 of the estrous cycle (low estrogen, low UBF). Arterial measurements included initial tone (baseline perfusion pressure [BPP] to a constant intraluminal flow) and increased tone after exposure to KCl, the contractility in response to the alpha 1-agonist phenylephrine, and specific uptake of 45Ca before and after exposure to the CE 4-hydroxylated estradiol (4OH-E2). Contractility of uterine arteries from Day 13 nonpregnant (NP) and Day 13 pregnant (P) gilts to phenylephrine were similar and significantly greater (p less than 0.01) than contractility of vessels from estrous gilts. The BPP and responses of uterine arteries from Day 13 NP gilts to KCl were greater (p less than 0.05) than the BPP and responses of arteries from Day 13 P and estrous gilts, which were similar to each other.(ABSTRACT TRUNCATED AT 250 WORDS)     

Surface artery volume pulse wave measurement - verification of a new method

The aim of this paper is to prove the possible reproducibility of measurement with a new developed device for artery elasticity monitoring and determining the standard of major pulse wave parameters. As a measurement sensor, a conic probe with thin convex membrane was used. This technique allows setting an arbitrary pressure to a measured surface artery. We measured pulse waves on the radial arteries of 108 individuals. We expected similar features in arterial wall elasticity. We concentrated primarily on the amount of subcutaneous fat. For the measured waves we evaluated five following pulse wave parameters: relative crest time, elasticity index, dicrotic wave attenuation, dicrotic wave time and interwave distance. There were no significant differences in measured pulse wave parameters among the tested groups of subjects.     

Light microscopic studies of the intramural coronary arteries in the trabecula septomarginalis of the right heart ventricle of cattle, swine and dwarf goats

In the Trabecula septomarginalis (moderator band) of cattle, pig and pygmy goat regularly till to 6 arteries are found, which traverse from the interventricular septum to the M. papillaris magnus. At these intramural coronary arteries (diameter 100-800 microns)--without any exception--musculoelastic intimal thickenings are recognizable, which often may result in concentric luminal narrowings of a high degree. The genesis and importance of the specificities in the wall structure of the moderator band arteries are discussed in relation to the intramural coronary arteries of the ventricular wall and papillary muscle as an adaptational reaction of the vascular wall to the extraordinary stress of these small vessels.     

Role of vasa vasorum in transendothelial solute transport in the coronary vessel wall: a study with cryostatic micro-CT

Using cryostatic microscopic computed tomography (micro-CT), we sought to determine the role of coronary vasa vasorum (VV) in transendothelial solute transport in arteries with normal and increased permeability due to high plasma cholesterol levels. In 6-mo-old pigs on a normal (n=23) and 2% high cholesterol (HC) diet (n=8), 2-cm segments of the proximal left anterior descending coronary arteries were removed in vivo after a selective injection of X-ray contrast solution. Harvesting of the specimens occurred at 0, 15, 25, 35, or 45 s after completion of the contrast injection. Specimens were snap frozen and scanned in our cryostatic micro-CT. The spatial distribution of contrast in the coronary artery wall was quantified using the CT images. Right coronary arteries were infused with Microfil to determine VV density (VV/mm2) and the cumulative lumen surface area (mm2/mm3). Transendothelial diffusion of contrast into the coronary vessel wall is a dynamic process starting at both the subintima and the adventitia. The subintimal opacification moves as a wave toward the adventitia, whereas the adventitial wave resolves. The coronary vessel wall in animals on a HC diet shows higher opacification than in normal coronary arteries without an increase of VV total luminal surface area. The loss of endothelial integrity in hypercholesterolemia significantly alters VV solute washin to, and washout from, the coronary artery wall.     

Evidence for greater burden of peripheral arterial disease in lower extremity arteries of spinal cord-injured individuals

Spinal cord injury leads to increased risk for cardiovascular disease and results in greater risk of death. Subclinical markers of atherosclerosis have been reported in carotid arteries of spinal cord-injured individuals (SCI), but the development of lower extremity peripheral arterial disease (PAD) has not been investigated in this population. The purpose of this study was to determine the effect of spinal cord injury on ankle-brachial index (ABI) and intima-media thickness (IMT) of upper-body and lower-extremity arteries. We hypothesized that the aforementioned measures of lower-extremity PAD would be worsened in SCI compared with controls and that regular participation in endurance exercise would improve these in both groups. To test these hypotheses, ABI and IMT were determined in 105 SCI and compared with 156 able-bodied controls with groups further subdivided into physically active and sedentary. ABIs were significantly lower in SCI versus controls (0.96 ± 0.12 vs. 1.06 ± 0.07, P < 0.001), indicating a greater burden of lower-extremity PAD. Upper-body IMTs were similar for brachial and carotid arteries in controls versus SCI. Lower extremity IMTs revealed similar thicknesses for both superficial femoral and popliteal arteries, but when normalized for artery diameter, individuals with SCI had greater IMT than controls in the superficial femoral (0.094 ± 0.03 vs. 0.073 ± 0.02 mm/mm lumen diameter, P < 0.01) and popliteal (0.117 ± 0.04 vs. 0.091 ± 0.02 mm/mm lumen diameter, P < 0.01) arteries. The ABI and normalized IMT of SCI compared with controls indicate that subclinical measures of lower-extremity PAD are worsened in individuals with SCI. These findings should prompt physicians to consider using the ABI as a screening method to detect lower-extremity PAD in SCI.     

Structure of pulsatile flow in a model of elastic cerebral aneurysm

This study examines the effect of aneurysmal wall elasticity on the structure of flow within an elastic aneurysm during pulsatile flow. We visualized flow structure in a model of an elastic saccular aneurysm located at the bifurcation of the anterior cerebral artery and extending to the anterior communicating artery, and measured changes in the diameter of the aneurysm wall during pulsatile flow using particle imaging velocimetry (PIV). We similarly measured these features during steady flow by PIV and found that dilation of the aneurysmal wall absorbed the dynamic energy within the aneurysm. Accordingly, aneurysm wall elasticity functions as a biocompatible reaction that relieves wall shear stress acting on the vascular wall during pulsatile flow, and should thus inhibit the development and rupture of an aneurysm.     

Heterogeneity in conduit artery function in humans: impact of arterial size

To determine whether conduit artery size affects functional responses, we compared the magnitude, time course, and eliciting shear rate stimulus for flow-mediated dilation (FMD) in healthy men (n = 20; 31 +/- 7 yr). Upper limb (brachial and radial) and lower limb (common and superficial femoral) FMD responses were simultaneously assessed, whereas popliteal responses were measured in the same subjects during a separate visit. Glyceryl trinitrate (GTN)-mediated responses were similarly examined. Edge detection and wall tracking of high-resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, were used to calculate conduit artery diameter, blood flow, and shear rate continuously across the cardiac cycle. Baseline artery size correlated inversely with the FMD response (r = -0.57, P < 0.001). Within-artery comparisons revealed a significant inverse correlation between artery size and FMD% for the radial (r = -0.66, P = 0.001), brachial (r = -0.55, P = 0.01), and popliteal artery (r = -0.48, P = 0.03), but not for the superficial and common femoral artery. Normalization of FMD responses for differences in eliciting shear rate did not abolish the between-artery relationship for artery function and size (r = -0.48, P < 0.001), suggesting that differences between artery function responses were not entirely due to size-related differences in shear rate. This was reinforced by a significant between-artery correlation for GTN responses and baseline artery size (r = -0.74, P < 0.001). In summary, systematic differences exist in vascular function responses of conduit arteries that differ in size. This raises the possibility that differences in artery size within or between individuals may influence functional responses.     

Influence of arterial wall-stenosis compliance on the coronary diagnostic parameters

Functional diagnostic parameters such as Fractional Flow Reserve (FFR), which is calculated from pressure measurements across stenosed arteries, are often used to determine the functional severity of coronary artery stenosis. This study evaluated the effect of arterial wall-stenosis compliance, with limiting scenarios of stenosis severity, on the diagnostic parameters. The diagnostic parameters considered in this study include an established index, FFR and two recently developed parameters: Pressure Drop Coefficient (CDP) and Lesion Flow Coefficient (LFC). The parameters were assessed for rigid artery (RR; signifying high plaque elasticity), compliant artery with calcified plaque (CC; intermediate plaque elasticity) and compliant artery with smooth muscle cell proliferation (CS; low plaque elasticity), with varying degrees of epicardial stenosis. A hyperelastic Mooney-Rivlin model was used to model the arterial wall and plaque materials. Blood was modeled as a shear thinning, non-Newtonian fluid using the Carreau model. The arterial wall compliance was evaluated using the finite element method. The present study found that, with an increase in stenosis severity, FFR decreased whereas CDP and LFC increased. The cutoff value of 0.75 for FFR was observed at 78.7% area stenosis for RR, whereas for CC and CS the cutoff values were obtained at higher stenosis severities of 81.3% and 82.7%, respectively. For a fixed stenosis, CDP value decreased and LFC value increased with a decrease in plaque elasticity (RR to CS). We conclude that the differences in diagnostic parameters with compliance at intermediate stenosis (78.7-82.7% area blockage) could lead to misinterpretation of the stenosis severity.     

Biomechanical response of femoral vein to chronic elevation of blood pressure in rabbits

Venous diseases like iliofemoral deep vein thrombosis and valvular dysfunction induce venous hypertension. To know the effects of the hypertension on venous mechanics, blood pressure in the left femoral vein in the rabbit was chronically elevated by the constriction of the left external iliac vein. Wall dimensions and biomechanical properties of the femoral vein were studied in vitro at 1, 2, or 4 wk after surgery. Blood pressure measured immediately before the animal was killed was significantly higher in the left femoral vein than in the sham-operated, contralateral vein. Wall thickness was increased by blood pressure elevation even at 1 wk, which restored circumferential wall stress to a control level. The stress was kept at normal up to 4 wk. Vascular tone and vascular contractility were increased by the elevation of blood pressure; however, wall elasticity and compliance were kept at a normal level. These results are very similar to those observed in hypertensive arteries, indicating that not only arteries but veins optimally operate against blood pressure elevation.     

Concentration polarization of atherogenic lipids in the arterial system

Nomenclature c, Normalized LDL concentration (C*/C0); C0, incoming (bulk) LDL concentration (gr/cm3); Cw, LDL concentration on the luminal surface (gr/cm3); ,wC time average value of LDL concentration on the luminal surface (gr/cm3); D, diffusion coef-ficient of LDL (cm2/s); Q, blood flow rate (mL/s); 0R, average internal radius of the artery (cm); Re, Reynolds number (002/Run); Sc, Schmidt number (/Dn); t, normalized time (00*/tuR); u, normalized axial velocity (0*/uu); 0u, time a…     

Localization of the permeability barrier to solutes in isolated arteries by confocal microscopy

Endothelial cells are covered by a surface layer of membrane-associated proteoglycans, glycosaminoglycans, glycoproteins, glycolipids, and associated plasma proteins. This layer may limit transendothelial solute transport. We determined dimension and transport properties of this endothelial surface layer (ESL) in isolated arteries. Rat mesenteric small arteries (diameter approximately 150 microm) were isolated and cannulated with a double-barreled -pipette on the inlet side and a regular pipette on the outlet side. Dynamics and localization of intra-arterial fluorescence by FITC-labeled dextrans (FITC-Deltas) and the endothelial membrane dye DiI were determined with confocal microscopy. Large FITC-Delta (148 kDa) filled a core volume inside the arteries within 1 min but was excluded from a 2.6 +/- 0.5-microm-wide region on the luminal side of the endothelium during 30 min of dye perfusion. Medium FITC-Delta (50.7 kDa) slowly penetrated this ESL within 30 min but did not permeate into the arterial wall. Small FITC-Delta (4.4 kDa) quickly passed the ESL and accumulated in the arterial wall. Prolonged luminal fluorochrome illumination with a bright mercury lamp destroyed the approximately 3-microm exclusion zone for FITC-Delta 148 within a few minutes. This study demonstrates the presence of a thick ESL that contributes to the permeability barrier to solutes. The layer is sensitive to phototoxic stress, and its damage could form an early event in atherosclerosis.     

Microscopic anatomy of the thin-walled vessels leaving the heart of the lobster Homarus americanus: anterior median artery

Abstract. The anterior median artery is an unpaired vessel that leaves the anterior end of the lobster ( Homarus americanus ) heart and supplies hemolymph to the brain, the antennae, and the eyestalks. This vessel has a trilaminar organization, consisting of a tunica interna with elastic fibrils, a tunica intermedia represented by a bilayered cell mass, and a tunica externa with collagen fibrils. The exposed ends of the medial cells in the tunica intermedia exhibit small, diffuse bundles of microfilaments that are penetrated by microtubules. These bundles have a circumferential or a slightly oblique orientation relative to the lumen of the vessel. The precise role of the microfilaments is unresolved. If the irregularly shaped bundles are static structures, they might contribute to the non-linear elasticity of the artery. Alternatively, if they generate force, a coordinated contraction of the medial cells might reduce the luminal diameter of the artery and, thus, retard hemolymph flow. Microfilaments of the medial cells anchor to subplasmalemmal filamentous mats, some of which are integral to intermediate junctions and some of which are associated with unbounded cell membranes (hemi-intermediate junctions). Contraction of the microfilament-bearing cells would have to occur without the benefit of nervous innervation or the participation of communicating (gap) junctions. If cell contractility is confirmed, a reclassification of the anterior median artery, from capacitance vessel to resistance vessel, is in order, and the bilayered cell mass in the tunica intermedia would likely qualify as the first unstriated muscle found in crustaceans.     

Resveratrol Improved Flow-Mediated Outward Arterial Remodeling in Ovariectomized Rats with Hypertrophic Effect at High Dose

Objectives

Chronic increases in blood flow in resistance arteries induce outward remodeling associated with increased wall thickness and endothelium-mediated dilatation. This remodeling is essential for collateral arteries growth following occlusion of a large artery. As estrogens have a major role in this remodeling, we hypothesized that resveratrol, described as possessing phytoestrogen properties, could improve remodeling in ovariectomized rats.

Methods

Blood flow was increased in vivo in mesenteric arteries after ligation of adjacent arteries in 3-month old ovariectomized rats treated with resveratrol (5 or 37.5 mg/kg per day: RESV5 or RESV37.5) or vehicle. After 2 weeks arterial structure and function were measured in vitro in high flow (HF) and normal flow (NF) arteries isolated from each rat.

Results

Arterial diameter was greater in HF than in NF arteries in ovariectomized rats treated with RESV5 or RESV37.5, not in vehicle-treated rats. In mice lacking estrogen receptor alpha diameter was equivalent in HF and NF arteries whereas in mice treated with RESV5 diameter was greater in HF than in NF vessels. A compensatory increase in wall thickness and a greater phenylephrine-mediated contraction were observed in HF arteries. This was more pronounced in HF arteries from RESV37.5-treated rats. ERK1/2 phosphorylation, involved in hypertrophy and contraction, were higher in RESV37.5-treated rats than in RESV5- and vehicle-treated rats. Endothelium-dependent relaxation was greater in HF than in NF arteries in RESV5-treated rats only. In HF arteries from RESV37.5-treated rats relaxation was increased by superoxide reduction and markers of oxidative stress (p67phox, GP91phox) were higher than in the 2 other groups.

Conclusion

Resveratrol improved flow-mediated outward remodeling in ovariectomized rats thus providing a potential therapeutic tool in menopause-associated ischemic disorders. This effect seems independent of the estrogen receptor alpha. Nevertheless, caution should be taken with high doses inducing excessive contractility and hypertrophy in association with oxidative stress in HF arteries.