Swine Artery Research Articles

AS-267 Is There Any Anatomic Basis for Off Label Use of Coronary Artery Stent in Renal Artery in Swine?

Coronary drug-eluting stents have been implanted in small renal arteries (<5.0mm) to reduce restenosis. The aim of this study is to investigate the anatomic basis for off label use of coronary stent in renal artery in swine.

Blunted pulmonary dilation during exercise in familial hypercholesterolemic swine does not involve endothelin‐1

Pulmonary dilation during exercise aids in effective gas exchange; however, the effect of hypercholesterolemia on this dilation is unclear. Hypercholesterolemia likely causes endothelial dysfunction and may hamper pulmonary dilation during exercise. We investigated pulmonary hemodynamics during exercise using chronically instrumented control (n=5) and familial hypercholesterolemic (FH; n=4) swine. Cholesterol levels were elevated in FH compared to control swine (651±13 v 59±4 mg/dl). Resting pulmonary vascular conductance (PVC) was similar between FH and control swine (8±1 v 9±1 ml/min/kg/mmHg) and pulmonary artery pressure was elevated in FH swine (28±2 v 12±1 mmHg). Graded treadmill exercise resulted in increased PVC in control swine (12.2±0.8 ml/min/kg/mmHg at 3mph) which was blunted in FH swine (10.0±0.8 ml/min/kg/mmHg). We further examined whether increased pulmonary constriction via endothelin-1 (ET-1) accounted for blunted pulmonary dilation in FH swine. Pulmonary responses to exercise were determined after treatment with the mixed ET-1 receptor antagonist tezosentan. Blockade of ET receptors significantly reduced resting PVC in both groups; however, responses to exercise were principally unchanged. Thus, chronic hypercholesterolemia attenuates pulmonary dilation during exercise, but not via enhanced pulmonary constriction to ET-1. Supported by NIH HL52490 and NHF 2000T042.

Successful Transfection of Genes Using AAV-2/9 Vector in Swine Coronary and Peripheral Arteries

Gene therapy has attracted attention for its potential to treat several cardiovascular diseases. The use of adeno-associated viral (AAV) vectors to facilitate therapeutic gene transfer to suppress intimal hyperplasia is a promising concept. The objective of this study was to analyze the in vivo transduction of a novel recombinant AAV-2/9 vector with SM22α promoter, containing β-galactosidase gene (LacZ) or green fluorescent protein (GFP) as reporter genes, to the medial layer smooth muscle cells (SMCs) of swine coronary and peripheral arteries. The AAV-2/9 vector containing SM22α (1 × 10(13) pfu) were administered into carotid/femoral/coronary arteries of domestic swine using irrigating balloon catheter-based gene delivery. Following gene transfer, cryosections of arteries were processed for X-Gal and GFP analysis. Fluorescence microscopy and Western blotting were done to analyze the GFP expression in the SMCs. LacZ mRNA expression was visualized in the medial layer 7 d after vector administration. The GFP expression was detected at day 7 and lasted for at least 2 mo showing the longer-lasting expression of the AAV-2/9 vector. Control arteries did not show any expression of GFP or LacZ. There was no significant effect of AAV-2/9 viral transduction on serum amylase, fibrinogen, and serum CRP levels. These finding support the use of AAV-2/9 as a vector to effectively transduce a gene in SMCs of coronary and peripheral arteries without causing inflammation.

Experimental study and constitutive modelling of the passive mechanical properties of the porcine carotid artery and its relation to histological analysis: Implications in animal cardiovascular device trials

The present study focusses on the determination, comparison and constitutive modelling of the passive mechanical properties of the swine carotid artery over very long stretches in both proximal and distal regions. Special attention is paid to the histological and mechanical variations of these properties depending on the proximity to the heart. The results can have clinical relevance, especially in the research field of intravascular device design. Before the final clinical trials on humans, research in the vascular area is conducted on animal models, swine being the most common due to the similarities between the human and swine cardiovascular systems as well as the fact that the swine size is suitable for testing devices, in this case endovascular carotid systems. The design of devices usually involves numerical techniques, and an important feature is the appropriate modelling of the mechanical properties of the vessel. Fourteen carotid swine arteries were harvested just after sacrifice and cyclic uniaxial tension tests in longitudinal and circumferential directions were performed for distal and proximal samples. The stress–stretch curves obtained were fitted with a hyperelastic anisotropic model. Stress-free configuration states were also analyzed. Finally, human and swine samples were processed in a histological laboratory and images were used to quantify their microconstituents. The statistical analysis revealed significant differences between the mechanical behavior of proximal and distal locations in the circumferential but not in the longitudinal direction. Circumferential direction samples show clear differences both in residual stretches and tensile curves between the two locations, while the features of longitudinal specimens are independent of the axial position. The statistical analysis provides significant evidence of changes depending on the position of the sample, mainly in elastin and SMC quantification.

Preliminary Study of the Effects of Smectite Granules (WoundStat) on Vascular Repair and Wound Healing in a Swine Survival Model

WoundStat (WS) (TraumaCure, Bethesda, MD) is a topical hemostatic agent that effectively stops severe hemorrhage in animal models. To the best of our knowledge, no survival study has been conducted to ensure long-term product safety. We evaluated vascular patency and tissue responses to WS in a swine femoral artery injury model with survival up to 5 weeks. Anesthetized swine received a standardized femoral artery injury with free hemorrhage for 45 seconds followed by WS application. One hour after application, the WS was removed, the wound copiously irrigated, and the artery repaired using a vein patch. Six groups of three animals received WS and were killed either immediately after surgery or at weekly intervals up to 5 weeks. Three control animals were treated with gauze packing and direct pressure followed by identical vascular repair and survival for 1 week. At the time of killing, angiograms were performed, and tissue was collected for histopathology. Hemostasis was complete in all WS animals. All animals survived the procedure, and there were no clinically evident postoperative complications. Vascular repairs were angiographically patent in 15 of 18 animals (83%) receiving WS. Histopathologic examination of WS animals revealed severe diffuse fibrogranulomatous inflammation, early endothelial degeneration with subsequent intimal hyperplasia, moderate myocyte necrosis, and fibrogranulomatous nerve entrapment with axonal degeneration. Although an effective hemostatic agent, WS use was associated with a substantial local inflammatory response and neurovascular changes up to 5 weeks postinjury.

Shedding Light on Bioabsorbable Stent Struts Seen by Optical Coherence Tomography in the ABSORB Trial

Optical coherence tomography (OCT) is an emerging intracoronary imaging technology that obtains depth-resolved images of light backscattered from the coronary wall with an axial resolution of ≈10 μm. First demonstrated in 2001 in patients,1 intracoronary OCT is now commercially available and is beginning to be adopted in cardiac catheterization laboratories worldwide. An important application of OCT is the investigation of intracoronary stents; ≈100 articles have been published over the past 5 years in which OCT was used for this purpose. OCT is well suited for such studies because (1) its contrast and resolution enable delineation of fine details including device and arterial wall structures; (2) stent healing occurs near the luminal surface, where OCT is most effective; and (3) relative to other imaging modalities, OCT has fewer imaging artifacts that interfere with the appearance of stent struts and surrounding tissues. Article see p 2288 Recently, researchers have found that OCT may also be well suited for investigating the fate of bioabsorbable stents, including bioabsorbable vascular scaffolds (BVS).2,–,9 These new devices are of particular interest because they offer the potential to facilitate coronary revascularization while subsequently being dissolved and assimilated into the artery wall. Resorption in this manner may overcome many of the limitations of bare-metal and drug-eluting stents by leaving behind a revascularized coronary artery without any residual “foreign” material that can promote restenosis or precipitate late stent thrombosis. Given the recent introduction of new generations of bioabsorbable stents, it is critical to understand and monitor …

E0231 Polymer-free sirolimus and probucol-eluting stent for renal artery: an initial experience in swine

ObjectiveBare metal stent (BMS) implantation can resolve renal artery stenosis successfully, but in-stent restenosis does occur, especially in small diameter renal arteries (<5.0 mm). The aim of this study is...

E0710 Is there any anatomic basis for off label use of coronary artery stent in renal artery in swine?

ObjectiveCoronary drug-eluting stents have been implanted in small renal arteries (<5.0 mm) to reduce restenosis. The aim of this study is to investigate the anatomic basis for off label use...

Prolonged Treadmill Running Promotes Development Of Collateral Arteries In Swine With Femoral Artery Occlusion.

Prolonged Treadmill Running Promotes Development Of Collateral Arteries In Swine With Femoral Artery Occlusion.

Predictors of stent failure in a swine model: role of implant site, implant material, and musculoskeletal motion

Purpose: Stent failure modes, such as device migration and fracture, may be related to the implant material and environment, including normal motion of the implant site. The kinematics of pelvic vascular motion in swine was studied with and without implanted stents to define these parameters in a preclinical implant model. Long-term stent integrity was evaluated in swine coronary and femoral arteries to identify material and site-specific effects. Materials and methods: The motion and deformation of pelvic vessels during movement were evaluated by CTA with the animals (n=5) under anesthesia and the hindlimbs (i) fully extended and (ii) fully flexed at the hip. Bare metal stainless steel stents (BMS SS) were implanted in the femoral artery of swine (n=5) and CTA performed. The in vivo vessel deformation with and without a stent was quantified with image analysis (cvSim) of the CTA. Three-dimensional deformation of the normal and stented vessels was characterized as changes in length, diameter, curvature, and torsion. Nitinol (NiTi) and SS stents were implanted in the lateral circumflex femoral (LCxF) (n=12) and coronary arteries (n=12): overlapping NiTi-SS and either single NiTi or SS BMS. Serial CT and fluoroscopy were performed for up to 180 days with radiographs and SEM of explanted stents. Results: As the leg moves from full extension to full flexion at the hip, the LCxF shortens 31%, increases diameter up to 16%, increases peak curvature (1/cm) from 0.28 to 0.85 and rotates 92 degrees along its length. Placement of a SS stent in this vessel reduced peak curvature (40%) and rotation (23%) with minor changes in length and diameter, over the same range of motion. All SS stents in the pelvis fractured. In the coronary arteries, 75% of the overlapped SS stents fractured with no fracture of single SS stents. Over time, there was increasing distraction of the stent fragments in both implant sites. No NiTi stents fractured. Explant SEM showed no corrosion in the single stents, but numerous areas of pitting corrosion in overlapped stents ranging from shallow to deep pits extending across the strut thickness. Conclusion: Overlapping of stents as well as nonradial deformation in the femoral was associated with SS stent fracture. The fracture modes were defined as bending and mixed mode. Device failures may in part be due to the wide range of physical forces and deformation imposed on overlapped and single stents. Selection of an appropriate implant site should consider the potential motion and deformation characteristics of the vessel, and the intended clinical implant site.

Efficiency of Drug Delivery to the Coronary Arteries in Swine Is Dependent on the Route of Administration: Assessment of Luminal, Intimal, and Adventitial Coronary Artery and Venous Delivery Methods

To compare the efficiency of five different drug delivery methods to the coronary artery in swine. A nanoparticle-albumin-bound, nonradioactive isotopic marker was administered within the left anterior descending coronary artery (LAD) through a microinfusion catheter (MIC: adventitial, n = 8, and luminal, n = 4), a porous drug infusion balloon (DIB: intimal, n = 4), and a straight catheter (SC: luminal, n = 2) and within the superior vena cava (SC: intravenous, luminal, n = 2). The distribution of the marker in heart, lung, liver, kidney, muscle, blood, urine, and bile was determined 68-84 minutes after delivery. The heart was sectioned into six axial slices and each slice divided into four quadrants. The marker content was assayed by neutron bombardment and the total counts of disintegrations per minute (DPM) expressed as a percentage of the control for each device delivery control. After luminal delivery with the nonactuated MIC (MIC-NA) or intimal delivery with the DIB, 0.17% ± 0.07 and 0.39% ± 0.09, respectively, less than 0.39% of the total marker was detected in the heart. After adventitial delivery with the actuated MIC (MIC-A), 63.1% ± 9.9 of the total marker was detected in the heart. Marker was only detected in quadrants containing the coronary LAD, with the highest level in the middle slice and lower marker levels in consecutive proximal and distal heart slices. The nonactuated MIC-NA and DIB drug infusion balloon patterns of marker distribution were similar to those of actuated MIC-A, although with reduced levels. These delivery methods were also associated with considerably more marker detected in the lungs and liver: at least 22% compared with 1.34% ± 1.34 for the actuated MIC-A There was one delivery failure with the actuated MIC. Catheter-based adventitial delivery with the MIC-A represents a more efficient delivery method for retention of vascular therapeutics.

O-025 The Trevo device: preclinical data of a novel stroke thrombectomy device in two different animal models of arterial thrombo-occlusive disease

IntroductionThe currently available mechanical devices fail to achieve recanalization in as many as 20–40% of proximal arterial occlusion strokes. We now report on the preclinical evaluation of the safety and...

Drug-Coated Balloons for the Prevention of Vascular Restenosis

From early in the history of percutaneous cardiovascular intervention, restenosis has been one of the most important clinical and biological measures of success, and a great deal of effort has been put into understanding the mechanisms responsible.1,2 Restenosis is the result of the interaction of a variety of mechanical and biological processes that begin immediately after balloon injury, including early vessel recoil,3,4 negative vascular remodeling,5 and excessive neointimal proliferation.5–7 The most important limitations of balloon angioplasty, abrupt vessel closure resulting from elastic recoil and occlusive plaque dissection, were effectively solved by the introduction of balloon-expandable stents.8 However, in-stent restenosis (ISR), the result of the initial injury and the vascular response to the implanted metallic prosthesis leading to excessive neointimal proliferation, remained as the most important cause of failure of these devices.9,10 Drug-eluting stents (DES) effectively reduced ISR by addressing the biological mechanisms of neointimal proliferation and have become the mainstay of the interventional treatment of coronary atherosclerotic disease.11 However, the demonstrated efficacy of DES is balanced by the small but unpredictable risk of very late stent thrombosis thought to be due to delayed vascular healing resulting from either the initial antiproliferative effect (and associated late acquired incomplete stent apposition) or a hypersensitivity reaction to the drug, polymer coating, or their combination.12,13 Moreover, beyond the coronary vasculature, there has been a paucity of effective therapies to manage restenosis after intervention. In recent years, drug-coated balloons (DCBs) have emerged as a therapeutic alternative in the interventional field.14 With this technology, short-term transfer of antiproliferative drugs to the arterial wall is achieved without the requirement of an implanted drug delivery system, thus potentially reducing the untoward effects associated with polymer-based stent technologies. In small clinical randomized trials, paclitaxel-coated balloons have been shown to be …

Effects of exercise training on cellular mechanisms of endothelial nitric oxide synthase regulation in coronary arteries after chronic occlusion

Exercise training enhances agonist-mediated relaxation in both control and collateral-dependent coronary arteries of hearts subjected to chronic occlusion, an enhancement that is mediated in part by nitric oxide. The purpose of the present study was to elucidate exercise training-induced adaptations in specific cellular mechanisms involved in the regulation of endothelial nitric oxide synthase (eNOS) in coronary arteries of ischemic hearts. Ameroid constrictors were surgically placed around the proximal left circumflex coronary artery (LCX) of adult female Yucatan miniature swine. Eight weeks postoperatively, animals were randomized into sedentary (pen-confined) or exercise training (treadmill run; 5 days/wk; 14 wk) protocols. Coronary artery segments ( approximately 1.0 mm luminal diameter) were isolated from collateral-dependent (LCX) and control (nonoccluded left anterior descending) arteries 22 wk after ameroid placement. Endothelial cells were enzymatically dissociated, and intracellular Ca(2+) responses (fura 2) to bradykinin stimulation were studied. Immunofluorescence and laser scanning confocal microscopy were used to quantify endothelial cell eNOS and caveolin-1 cellular distribution under basal and bradykinin-stimulated conditions. Immunoblot analysis was used to determine eNOS, phosphorylated (p)-eNOS, protein kinase B (Akt), pAkt, and caveolin-1 protein levels. Bradykinin-stimulated nitrite plus nitrate (NOx; nitric oxide metabolites) levels were assessed via HPLC. Exercise training resulted in significantly enhanced bradykinin-mediated increases in endothelial Ca(2+) levels, NOx levels, and the distribution of eNOS-to-caveolin-1 ratio at the plasma membrane in endothelial cells of control and collateral-dependent arteries. Exercise training also significantly increased total eNOS and phosphorylated levels of eNOS (pSer(1179)) in collateral-dependent arteries. Total eNOS protein levels were also significantly increased in collateral-dependent arteries of sedentary animals. These data provide new insights into exercise training-induced adaptations in cellular mechanisms of nitric oxide regulation in collateral-dependent coronary arteries of chronically occluded hearts that contribute to enhanced nitric oxide production.

Gene expression differences in the brachial and femoral arteries of Rapacz Familial Hypercholesterloemic swine at birth are related to atherosusceptibility

The mechanisms underlying the greater prevalence of atherosclerosis in the femoral compared to brachial arteries of both humans and quadrupeds are still unclear. We hypothesized that brachial and femoral differences in genes associated with atherosclerosis occur during vascular development. To test this hypothesis five femoral and brachial arteries were harvested from one week old Rapacz swine. The presence of atherosclerosis was quantified through histological staining (SudanIV, VVG, H/E). Total RNA was isolated for microarray analysis using a Macherey‐Nagel NucleoSpin RNAII kit. Gene expression was quantified by Affymetrix GeneChip Porcine Genome Arrays. Bioconductor was used to run Robust Multi‐chip Average (RMA) expression values on a paired t‐test model. No atherosclerotic disease was detected in either the brachial or femoral arteries. Of the 16526 expressed genes, RMA analysis revealed that 71 genes were differentially expressed to a significant level (FDR&lt;0.05 + min. 2fold difference) in the brachial and femoral arteries. 29 transcripts had higher gene expression in the femoral arteries, while 42 were higher in the brachial arteries. In conclusion, inherent gene expression differences between the brachial and femoral arteries of swine exist at birth and may contribute to the unequal distribution of atherosclerosis between these vasculatures later in life.

Coronary artery microvascular narrowing downstream of stent implantation

The aim of this study was to determine the effects of stenting on downstream coronary microvessel structure in lean Ossabaw miniature swine. Bare metal stents were deployed in the left anterior descending (LAD) coronary artery of lean male Ossabaw miniature swine having a genetic propensity to obesity and metabolic syndrome. Four weeks after stent implantation, coronary microvessels (&lt;150 μm diameter) downstream of either non‐stented (n=3) or stented (n=3) LAD were carefully isolated and mounted on a pressure myograph. After a 30‐minute equilibration period, coronary microvessel wall thickness and diameters were measured over a range of pressures (0–125 mmHg). Coronary microvessels downstream of bare metal stents exhibited a 20% decrease in luminal diameters (Non‐Stented: 123.8 ± 9.2 μm vs. Stented: 99.0 ± 12.1 μm p &lt; 0.05), while wall thicknesses were preserved (Non‐Stented: 14.1± 1.2 μm vs. Stented: 13.5 ± 0.8 μm p &gt; 0.05). The decrease in external diameter did not achieve statistical significance (Non‐Stented: 152.0 ± 10.7 μm vs. Stented: 126.0 ± 13.3 μm p = 0.05) These data suggest that bare metal stent deployment in the LAD causes downstream coronary microvessels to undergo eutrophic inward remodeling, which may contribute to chronically impaired coronary flow reserve. Support: NIH HL056046, Nationwide Children's Hospital to PAL; NIH RR013223, HL062552, UL1 RR025761, Purina TestDiet to MS.

Adeno‐associated Virus 9 Vector in the Gene Therapy of Occlusive Vascular Diseases

We analyzed the efficiency and duration of transfection of AAV9 vector containing SM22α promoter with either eGFP or LacZ as reporter genes. The vectors (1 × 1012 pfu) were incorporated into coronary and carotid arteries of swine using microporous balloon catheter‐based gene delivery approach. Segments from all vessels were excised at various time points and immediately frozen for mRNA/protein expression or were processed for frozen sections for X‐Gal, GFP or H&amp;E staining. GFP was visualized distinctly in the medial layer. Frozen sections were stained and β‐galactosidase gene transfer was assessed by blue‐stained cell nuclei. The endothelial and adventitial layers were carefully scraped off from the harvested vessel and total RNA was isolated from the remaining medial layer for qPCR. In the medial layer of coronary and femoral arteries LacZ mRNA expression was visualized 7 days after vector administration. The GFP mRNA expression was detected at 7 days and lasted for at least 2 months showing the prolonged expression of the AAV9‐vector. The GFP expression was confirmed by Western blot. Control arteries did not show any expression of GFP or LacZ. These findings support the use of AAV9 as a vector to effectively transduce a gene in coronary arteries.(Supported by LB692 Nebraska Tobacco settlement Funds and NHLBI‐sponsored Penn Vector Core, University of Pennsylvania)

Freeze–Thaw Induced Biomechanical Changes in Arteries: Role of Collagen Matrix and Smooth Muscle Cells

Applications involving freeze-thaw, such as cryoplasty or cryopreservation can significantly alter artery biomechanics including an increase in physiological elastic modulus. Since artery biomechanics plays a significant role in hemodynamics, it is important to understand the mechanisms underlying these changes to be able to help control the biomechanical outcome post-treatments. Understanding of these mechanisms requires investigation of the freeze-thaw effect on arterial components (collagen, smooth muscle cells or SMCs), as well as the components' contribution to the overall artery biomechanics. To do this, isolated fresh swine arteries were subjected to thermal (freeze-thaw to -20 degrees C for 2 min or hyperthermia to 43 degrees C for 2 h) and osmotic (0.1-0.2 M mannitol) treatments; these treatments preferentially altered either the collagen matrix (hydration/stability) or smooth muscle cells (SMCs), respectively. Tissue dehydration, thermal stability and SMC functional changes were assessed from bulk weight measurements, analyses of the thermal denaturation profiles using Fourier transform infrared (FTIR) spectroscopy and in vitro arterial contraction/relaxation responses to norepinephrine (NE) and acetylcholine (AC), respectively. Additionally, Second Harmonic Generation (SHG) microscopy was performed on fresh and frozen-thawed arteries to directly visualize the changes in collagen matrix following freeze-thaw. Finally, the overall artery biomechanics was studied by assessing responses to uniaxial tensile testing. Freeze-thaw of arteries caused: (a) tissue dehydration (15% weight reduction), (b) increase in thermal stability (approximately 6.4 degrees C increase in denaturation onset temperature), (c) altered matrix arrangement observed using SHG and d) complete SMC destruction. While hyperthermia treatment also caused complete SMC destruction, no tissue dehydration was observed. On the other hand, while 0.2 M mannitol treatment significantly increased the thermal stability (approximately 4.8 degrees C increase in denaturation onset), 0.1 M mannitol treatment did not result in any significant change. Both 0.1 and 0.2 M treatments caused no change in SMC function. Finally, freeze-thaw (506+/-159 kPa), hyperthermia (268+/-132 kPa) and 0.2 M mannitol (304+/-125 kPa) treatments all caused significant increase in the physiological elastic modulus (Eartery) compared to control (185+/-92 kPa) with the freeze-thaw resulting in the highest modulus. These studies suggest that changes in collagen matrix arrangement due to dehydration as well as SMC destruction occurring during freeze-thaw are important mechanisms of freeze-thaw induced biomechanical changes.

Effects of extract of Bulbus Allii Caespitosi on cardiocyte viability of swines with myocardial reperfusion injury evaluated by 18F-fluorodeoxyglucose positron emission tomography/computed tomography

To investigate the effects of extract of Bulbus Allii Caespitosi on cardiocyte viability of swines with myocardial reperfusion injury by analyzing the 18F-fluorodeoxyglucose ((18)F-FDG) position emission tomography (PET) imaging. Twenty-four swines were randomly divided into sham-operated group, untreated group, trimethazine group and extract of Bulbus Allii Caespitosi group. Myocardial reperfusion injury was induced by plugging the anterior descending coronary artery of swine with sacculus. Bulbus Allii Caespitosi or trimetazidine was given twice daily for 28 days. Then myocardial perfusion was detected with (18)F-FDG PET/CT and the radioactivity distribution was evaluated. Compared with the untreated group, Bulbus Allii Caespitosi and trimetazidine could improve the activity of myocardial cells after myocardial infarction (P<0.01), and there were no significant differences between Bulbus Allii Caespitosi and trimetazidine (P>0.05). Bulbus Allii Caespitosi can improve myocardial metabolism after ischemia and reperfusion in swines.

Role of shear stress on nitrite and NOS protein content in different size conduit arteries of swine

Inherent fundamental difference exists among arteries of different sizes. The purpose of this study was to evaluate the relation between regional difference of wall shear stress (WSS) in various sizes arteries and contents of nitrite and NO synthase (NOS) isoforms. Five different conduit arteries in a wide range of diameter (1-8 mm) were examined in the hind limbs of 13 pigs. Blood flow rate and outer diameter were measured in vivo to determine WSS. Arterial tissues were harvested for the measurement of nitrite and NOS protein contents. The concentration of nitrite, a product of NO synthesis, was determined by high-performance liquid chromatography method. Western blot analysis was used to assess the protein contents of endothelial NOS (eNOS), inducible NOS (iNOS) and neuronal NOS (nNOS). Our data show that WSS increases with a decrease in artery diameter. Nitrite level increases with increasing WSS and hence decreases with artery diameter. The eNOS protein contents decrease with an increase in diameter. No significant difference for iNOS and nNOS protein contents was found with different artery diameter. A significant positive correlation between tissue nitrite and eNOS protein contents was also observed. Finally, the WSS-normalized eNOS is not significantly different in various size vessels. Regional difference in blood flow has no effect on iNOS and nNOS protein contents in these conduit arteries. Regional difference in eNOS expression and nitrite contents may be related to the WSS-induced NO by the endothelium under normal physiological conditions.