bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Smooth Muscle Activation in Conduction of Vasodilation along Isolated Hamster Feed Arteries
Authors: Walker Bryan D. , Segal Steven S. 
Published: April 2003

Vasodilation originating within a muscle is conducted into feed arteries, but the determinants of conduction along feed arteries are undefined. We have investigated the effect of vasomotor tone on conducted vasodilation in feed arteries of the hamster retractor muscle. Unbranched segments (length, 2–3 mm) were isolated, cannulated, and studied in vitro at 37°C while pressurized to 25 mm Hg, 75 mm Hg (in vivo pressure), or 120 mm Hg in the absence and presence of norepinephrine (NE, 10<sup>–7</sup> <i>M</i> + 10<sup>–6</sup> <i>M</i> propanolol). Internal diameter decreased (p < 0.05) as pressure increased (85 ± 7, 73 ± 4, 66 ± 6 µm, respectively), confirming myogenic reactivity. Acetylcholine (ACh, 0.1 <i>M</i>) was delivered (1 µA, 500 ms) from a micropipette; vasomotor responses were recorded at the site of release (‘local’) and at distances up to 1,500 µm (‘conducted’) along the vessel. There were no responses to ACh at 25 mm Hg. However, dilations (diameter change, µm) were pronounced at 75 mm Hg (local: 22 ± 3; conducted: 18 ± 2, respectively), without further change at 120 mm Hg. NE constricted vessels (p < 0.05) at each pressure (to 65 ± 9, 57 ± 6, and 56 ± 8 µm, respectively); this enabled both local (14 ± 2 µm) and conducted (10 ± 1 µm) vasodilation at 25 mm Hg but was without effect on conduction at 75 or 120 mm Hg. Our findings indicate that conducted responses plateau at a physiological level of myogenic tone. Whereas NE had no effect on conduction under normal or hypertensive conditions, it enabled conduction during hypotension. We conclude that pressure and NE influence the ability of conducted vasodilation to govern muscle blood flow.
Assessment of Local Differences in Intima-Media Thickness in the Human Common Carotid Artery
Authors: Willekes Christine , Brands Peter J. , Willigers Jean M. , Hoeks Arnold P.G. , Reneman Robert S. 
Published: April 2003

Intimal thickening may be focal in nature and is especially found in areas with low shear rate. To be able to study the relation between intima-media thickness (IMT) and wall shear rate appropriately, a method to assess IMT locally is required. It was the aim of the present study to investigate the ability of a recently developed automated method to assess local differences in IMT, if any, in relatively short arterial segments. Therefore, intrasession interlocation differences in IMT were assessed at the posterior wall of the common carotid artery close to the bulb (0 mm) and 10 and 20 mm more upstream in terms of mean difference ± 2 standard deviations. Prior to this study we investigated the ability of the system to reproducibly assess IMT locally (intersession intralocation) in terms of repeatability coefficient (= 2 standard deviations). The measurements were performed in the common carotid artery 20 mm proximal to the bulb. The study was performed on young and older subjects presumed to be healthy. The intersession intralocation repeatability coefficient was 0.07 mm in the young group and 0.11 mm in the older group. The IMT close to the bulb (0 mm) was significantly larger (±0.050–0.065 mm) than that at the other locations in both age groups. We conclude that local IMT can be assessed reproducibly and local differences in wall morphology in short arterial segments can be studied reliably.
Leukocyte Margination in Alveolar Capillaries: Interrelationship with Functional Capillary Geometry and Microhemodynamics
Authors: Kuebler W.M. , Kuhnle G.E.H. , Goetz A.E. 
Published: April 2003

The pulmonary capillary microvasculature harbors a large pool of intravascularly marginated leukocytes. In this study, we investigated the interrelationship of leukocyte margination with characteristics of functional capillary geometry and microhemodynamics in alveolar capillary networks. In 22 anesthetized rabbits we assessed functional capillary density, average capillary length, red blood cell velocity and leukocyte kinetics in alveolar capillary networks in vivo by intravital fluorescence microscopy. In alveolar wall areas of 12,800 ± 1,800 μm<sup>2</sup>, we detected 3.6 ± 0.5 sticking leukocytes and 21.0 ± 1.9 functional capillary segments with an average capillary length of 35.7 ± 2.1 μm. We calculated that approximately 15% of functional capillary segments are blocked by marginated leukocytes. Leukocyte margination was predominantly observed in capillary networks characterized by a high functional capillary density, short capillary segments and low red blood cell velocities. The multitude of interconnected capillary channels in these networks may allow alveolar blood flow to bypass marginated leukocytes. Hence, this interrelationship may be relevant for maintenance of adequate alveolar perfusion and low capillary network resistance despite excessive leukocyte margination in the pulmonary microvasculature. Local microhemodynamic factors may play a regulatory role in the spatial distribution of leukocyte margination.
Moderate Hypoxia Increases Heat Shock Protein 90 Expression in Excised Rat Aorta
Authors: Almgren C.M. , Olson L.E. 
Published: April 2003

We hypothesized that heat shock protein 90 (HSP90) expression would be increased in vascular tissue exposed to a hypoxic stress that resulted in altered contractile function. We tested this hypothesis by subjecting excised rat aortic rings to a hypoxic stress that has been shown to reduce contractile force induced by arginine vasopressin (PO<sub>2</sub> ≈50 mm Hg for 1 h) and determining the effect on HSP90 expression. Concentration-response curves were determined for control and hypoxic excised rat aortic rings exposed to norepinephrine (n = 8) or KCl (n = 8). Hypoxia reduced the force generated in response to the highest concentration of each agonist. HSP90 expression was evaluated by immunoblotting (n = 6) and immunohistochemistry (n = 7). Both methods documented increased expression of HSP90 in hypoxic aortae as compared to controls. HSP90 expression was increased within the cytoplasm and in conjunction with the nucleus of vascular smooth muscle cells in the tunica media and also within vascular myointimal cells. We conclude that a hypoxic stress sufficient to induce contractile dysfunction increases HSP90 expression in rat aortic smooth muscle cells.
Effects of NO Synthase Inhibitors on the Synovial Microcirculation in the Mouse Knee Joint
Authors: Veihelmann A. , Krombach F. , Refior H.J. , Messmer K. 
Published: April 2003

Production of nitric oxide by the inducible NO synthase (iNOS) is known to be enhanced in chronic joint inflammation and osteoarthritis as well as aseptic loosening of joint prostheses. Initial studies yielded promising results after inhibition of the nitric oxide synthase (NOS). However, the effect of NOS inhibition has not been studied at the site of the primary function of NO, the microcirculation of the synovium in vivo. Using our recently developed model for the in vivo study of synovial microcirculation in the mouse knee joint, the effects of selective versus nonselective inhibition of iNOS were investigated by means of intravital fluorescence microscopy. After resection of the patella tendon, the synovial fatty tissue was exposed for intravital microscopy. Diameter of arterioles, functional capillary density (FCD), diameter of venules, venular red blood cell velocity and leukocyte-endothelial cell interaction were quantitatively analyzed before, and 10 and 60 min after intravenous injection of NOS inhibitors [selective iNOS inhibitor N-iminoethyl-<i>L</i>-lysine (L-NIL), and nonselective NOS inhibitor N<sup>G</sup>-nitro-<i>L</i>-arginine methyl ester (L-NAME)]. Our results demonstrate that L-NAME causes a significant decrease in the arteriolar diameter and FCD associated with an increase in the leukocyte accumulation in the synovium in vivo. In contrast, L-NIL neither altered the microhemodynamics nor the leukocyte-endothelial cell interaction in the synovium, indicating its potential use for selective inhibition of iNOS in joint inflammation. Using our method, further studies will provide new insights into the unknown effect of NOS inhibition on the synovial microvasculature in inflammatory joint disease in vivo.
Impaired Endothelium-Mediated Relaxation in Coronary Arteries from Insulin-Resistant Rats<footref rid="foot01"><sup>1</sup></footref>
Authors: Miller Allison W. , Katakam Prasad V.G. , Ujhelyi Michael R. 
Published: April 2003

<i>Objective:</i> The insulin resistance syndrome is associated with atherosclerosis and cardiovascular events; however, the underlying mechanism of vascular dysfunction is unknown. The purpose of the current study was to assess endothelium- and smooth-muscle-mediated vasodilation in isolated coronary arteries from insulin-resistant rats and to determine whether insulin resistance alters the activity of the specific endothelium-derived relaxing factors. <i>Methods:</i> Male Sprague-Dawley rats were randomized to insulin resistance or control. Insulin resistance was induced by a fructose-rich diet. After 4 weeks of diet, coronary arteries were removed and vascular function was assessed in vitro using videomicroscopy. Acetylcholine (10<sup>–9</sup>–3 × 10<sup>–5</sup> <i>M</i>)- or sodium-nitroprusside (10<sup>–9</sup>–3 × 10<sup>–4</sup> <i>M</i>)-induced relaxations were determined. To evaluate the role of the specific endothelium-derived relaxing factors, several inhibitors were used, including N-nitro-<i>L</i>-arginine (LNNA), charybdotoxin/apamin (CTX/apamin), and indomethacin. <i>Results:</i> Studies with nitroprusside showed that smooth-muscle-dependent relaxation did not differ between insulin resistance and control groups. In contrast, maximal relaxation (E<sub>max</sub>) to acetylcholine was decreased in the insulin resistance group (56 ± 7%) versus control (93 ± 3%). LNNA pretreatment further impaired E<sub>max</sub> in the IR group from 56 ± 7 to 17 ± 2% (p < 0.01). In control, E<sub>max</sub> was only slightly impaired by LNNA (93 ± 3 to 63 ± 6%; p < 0.05). The addition of CTX/apamin also decreased relaxation in the control group (93 ± 3 to 47 ± 7%; p < 0.05), whereas relaxation in insulin-resistant rats was not affected (45 ± 5% with CTX/apamin vs. 56 ± 7% with acetylcholine alone, NS). Pretreatment with indomethacin did not affect relaxation in either group, while pretreatment with the combination of LNNA and CTX/ apamin completely abolished relaxation in both groups. <i>Conclusions:</i> Endothelium-dependent relaxation is impaired in small coronary arteries from insulin-resistant rats. The mechanism of this defect is related to a decrease in an endothelium-dependent, nitric oxide/prostanoid-independent relaxing factor or endothelium-derived hyperpolarizing factor.
<i>L</i>-Arginine Availability Is Not Limiting for Nitric Oxide Generation from Recombinant Endothelial Nitric Oxide Synthase
Authors: Mohacsi Tibor , Mozes Geza , Sato Jun’ichi , Gloviczki Peter , Katusic Zvonimir , O’Brien Timothy 
Published: April 2003

<i>L</i>-Arginine (L-Arg) may be limiting for inducible nitric oxide synthase (NOS) activity and under certain circumstances, such as increased concentrations of a NOS inhibitor, may also be limiting for endothelial NOS activity. It is unknown if L-Arg is limiting for recombinant eNOS activity in the vascular wall after adenoviral mediated gene transfer. Our aim was to examine, if L-Arg is limiting for recombinant eNOS activity in the normal or atherosclerotic vessel wall. Rings of rabbit aorta from chow or cholesterol fed animals were transduced with adenovirus vector encoding eNOS (AdeNOS) or β-galactosidase (AdβGal). After 24 h, transgene expression was confirmed and vasomotor studies were performed in the absence or presence of L-Arg. During maximal contractions to phenylephrine (10<sup>–5</sup> <i>M</i>), L-Arg (3 m<i>M</i>) was added to the organ chamber for 30 min. Subsequently, relaxations to acetylcholine during half-maximal contractions were obtained. In the chow- and cholesterol-fed animals, relaxations were significantly enhanced in the NOS and NOS + L-Arg groups compared to the βGal and βGal + L-Arg groups. There was no difference between NOS and NOS + L-Arg or βGal and βGal + L-Arg rings from chow- or cholesterol-fed animals. While gene transfer of eNOS enhances endothelium-dependent vasorelaxation in the normal and atherosclerotic vessel wall, <i>L</i>-arginine is not limiting for recombinant eNOS activity.
Increased (Na+K+Cl) Cotransport in Rat Arterial Smooth Muscle in Deoxycorticosterone (DOCA)/Salt-Induced Hypertension
Authors: Brown R.A. , Chipperfield A.R. , Davis J.P.L. , Harper A.A. 
Published: April 2003

The inhibition by loop diuretics of K efflux (tracer <sup>86</sup>Rb) from the rat femoral arterial smooth muscle was measured in normotension and in DOCA-salt hypertension. The sensitivity sequence (bumetanide > piretanide > furosemide) was the characteristic pharmacological profile of (Na+K+Cl) cotransport. In hypertension, cotransport activity was 46% greater than in normotension and the sensitivity to loop diuretics was threefold less. Intracellular [K] and the Na, K and Cl permeability ratios and electrogenic Na pump activity were assessed electrophysiologically in normotension and hypertension. [K]<sub>i</sub> was lower in hypertension (173 m<i>M</i>) than normotension (198 m<i>M</i>) but the other parameters (P<sub>Na/Cl</sub> = 0.14, P<sub>Cl</sub>/P<sub>K</sub> = 0.19 and electrogenic pump = –8.3 mV in normotension) were not significantly different. Ionic permeabilities to Na, K and Cl were significantly lower in hypertension than normotension. Plasma [Na], but not [K], was higher in hypertension than normotension. The conclusion is that increased activation of (Na+K+Cl) cotransport in hypertension plays a major role in the elevation of [Cl]<sub>i</sub> and depolarisation of the membrane potential in vascular smooth muscle in DOCA-salt hypertension. The role of (Na+K+Cl) cotransport in vascular smooth muscle in this model of hypertension is discussed in relation to [Cl]<sub>i</sub>, depolarisation of the membrane potential and contraction and in relation to cell growth.
Effect of TGF-β<sub>1</sub> Antisense S-Oligonucleotide on Synthesis and Accumulation of Matrix Proteoglycans in Balloon Catheter-Injured Neointima of Rabbit Carotid Arteries
Authors: Merrilees Mervyn , Beaumont Brent , Scott Lesley , Hermanutz Valentin , Fennessy Paul 
Published: April 2003

Arterial matrix proteoglycans (PG) are necessary for the maintenance of viscoelastic properties of the vessel wall, but excess levels, particularly of versican and biglycan in primary and restenotic intimal thickenings, are correlated with increased tissue volume and with atherogenicity. There is good evidence that the primary stimulus to increased PG synthesis, including versican and biglycan, is transforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>). The aim of this study was to determine the effects of reducing endogenous TGF-β<sub>1</sub> on rates and patterns of PG synthesis and on versican, biglycan and decorin accumulation in vivo. Rabbit common carotid arteries subjected to balloon catheter injury were treated with a TGF-β<sub>1</sub> antisense phosphorothioate oligonucleotide applied in a pluronic gel to the adventitia. Control animals received a nonsense oligonucleotide or gel alone. TGF-β<sub>1</sub> antisense (1) significantly (p < 0.005) inhibited, at day 2, the balloon catheter-induced increase in TGF-β<sub>1</sub> mRNA relative to β-actin mRNA; (2) inhibited intimal thickening at 23 days by ∼40% (p < 0.05); (3) inhibited (p < 0.05) PG synthesis, measured by autoradiographic detection of [<sup>3</sup>H]glucosamine, in the media of day 2 ballooned carotids and in the subendothelial zone of day 23 neointima, and (4) decreased immunostaining intensity for versican (p < 0.03) and TGF-β<sub>1</sub> (p < 0.001) in the neointima. Biglycan was reduced to a lesser extent but not significantly and decorin was not affected. Proliferating cell nuclear antigen indices were variable and not significantly changed. These findings confirm a role for TGF-β<sub>1</sub> in developing neointima and demonstrate a specific effect on the synthesis, distribution, and accumulation of matrix PG, particularly versican.
Hirulog-1 Reduces Expression of Platelet-Derived Growth Factor in Neointima of Rat Carotid ArteryInduced by Balloon Catheter Injury
Authors: Xue Mengzhou , Fenton II John W. , Shen Garry X. 
Published: April 2003

Vascular restenosis is one of the major concerns for the treatment of atherosclerotic cardiovascular diseases using therapeutic vascular procedures. Hirulog-1, a synthetic thrombin inhibitor, effectively reduced ischemic events in coronary heart disease patients and caused less hemorrhagic complications compared to heparin. Thrombin stimulated the expression of platelet-derived growth factor (PDGF) in vascular cells. PDGF receptor blockers reduced angioplasty-induced restenosis in the swine model. The present study examined the effects of hirulog-1 on vascular stenosis, platelet deposition and the expression of PDGF in rat carotid arteries injured by balloon catheter. Multiple intravenous infusions of hirulog-1 (1 mg/kg/h for 4 h for 6 times), but not bolus injection or 1–2 times of infusion, reduced neointima/media ratio by 50% in balloon-injured carotid arteries compared to injured animals receiving saline alone. Activated partial thromboplastin time in hirulog-1-treated rats was significantly prolonged compared to saline controls but shorter than that in animals receiving heparin (50 U/kg/h). One of heparin-treated rat, but none of hirulog-1-treated, died from bleeding complication. Hirulog-1 injection transiently reduced platelet deposition on denuded intima visualized by scanning electron microscopy. Abundance of PDGF in neointima of injured carotid arteries detected by immunohistochemistry was significantly decreased following infusions of hirulog-1. The results suggest that balloon catheter injury induced neointima formation and the overexpression of PDGF in the neointima of rat carotid artery may be effectively suppressed by infusions with hirulog-1, a thrombin-specific inhibitor.
Prevention of Increases in Blood Pressure and Left Ventricular Mass and Remodeling of Resistance Arteries in Young New Zealand Genetically Hypertensive Rats: The Effects of Chronic Treatment with Valsartan, Enalapril and Felodipine
Authors: Ledingham Janet M. , Phelan Edward L. , Cross Marie A. , Laverty Richard 
Published: April 2003

The relative efficacy of three antihypertensive drugs in the prevention of further elevation of blood pressure (BP) and cardiovascular structural remodeling in 4-week-old genetically hypertensive (GH) rats was studied by means of two complementary methods, stereology and myography. Four to 10-week-old GH rats were treated with valsartan (10 mg/kg/day), enalapril (10 mg/kg/day) or felodipine (30 mg/kg/day). Untreated GH and normotensive control rats of Wistar origin served as controls. Tail-cuff systolic SBP was measured weekly and left ventricular (LV) mass determined at the end of the experiment. Mesenteric resistance arteries (MRA) were either fixed by perfusion, embedded in Technovit and sections stained for stereological analysis, or mounted on a wire myograph for structural and functional measurements. BP and LV mass were significantly reduced by all drugs; decreases in BP and LV mass were smaller after felodipine treatment. Valsartan and enalapril caused a decrease in BP to normotensive control values. Felodipine kept BP at the 4-week level and prevented further rise with age. Valsartan caused hypotrophic outward remodeling of MRA, enalapril eutrophic outward remodeling and felodipine hypotrophic remodeling. Myograph measurements showed remodeling of the same order. While all drugs lowered the media/lumen ratio in GH to normal, the outward remodeling after valsartan and enalapril indicates that valsartan and enalapril might be more effective in reversing the inward remodeling of resistance arteries found in essential hypertension.
Toxicity, Uptake Kinetics and Efficacy of New Transfection Reagents: Increase of Oligonucleotide Uptake
Authors: Axel Dorothea I. , Spyridopoulos Ioakim , Riessen Reimer , Runge Heike , Viebahn Richard , Karsch Karl R. 
Published: April 2003

Human arterial smooth muscle cell (haSMC) proliferation is stimulated by platelet-derived growth factor (PDGF) release of human arterial endothelial cells (haEC) whereas transforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>) secretion by haSMC promotes extracellular matrix formation. Inhibitory concepts with antisense oligonucleotides (ASO) against those growth factors might be promising, requiring, however, sufficient transfection efficacy. Thus, toxicity and efficacy of new transfection reagents were examined. MTT tests showed that high doses >1.6 μg/ml of the liposome Cytofectin GSV<sup>®</sup> (CF) and the dendrimer SuperFect<sup>®</sup> (SF) reduced mitochondrial activity of haEC after ≥4 h transfection whereas viability of haSMC was not influenced. DAC-30<sup>®</sup> showed significant toxic effects on haEC and haSMC at each dose after ≥4 h and Lipofectin<sup>®</sup> (LF) caused complete detachment of haEC and haSMC in medium containing 10% serum. Uptake studies demonstrated that ‘naked’ ASO were not incorporated intracellularly whereas transfection within CF or SF resulted in a strong cytoplasmic and nuclear labeling after 2–5 h. With DAC-30<sup>®</sup>, only a slight cytoplasmic fluorescence was found. SF caused an unexpected stimulation of endothelial PDGF-AB synthesis. Thus, CF was favored for inhibition studies. ELISA, Western and Northern blotting showed a significant inhibition of endothelial PDGF-B and smooth muscle TGF-β<sub>1</sub> mRNA expression and synthesis after transfection for 3–5 h using 0.1–1.0 μ<i>M</i> ASO versus control oligonucleotides. We conclude that Cytofectin GSV<sup>®</sup> is superior to the other transfection reagents, predominantly at haEC, showing an improved efficacy and less toxicity than the classical liposome Lipofectin<sup>®</sup>. Cytofectin GSV<sup>®</sup> might offer a promising tool for antisense strategies in the treatment of vascular disorders.
The Fractal Nature of Myocardial Blood Flow Emerges from a Whole-Organ Model of Arterial Network
Authors: Beard Daniel A. , Bassingthwaighte James B. 
Published: April 2003

Mammalian hearts exhibit a heterogeneous spatial distribution of blood flows, but flows in near-neighbor regions correlate strongly. Also, tracer <sup>15</sup>O-water washout after injection into the inflow shows a straight log-log relationship between outflow concentration and time. To uncover the role of the arterial network in governing these phenomena, morphometric data were used to construct a mathematical model of the coronary arterial network of the pig heart. The model arterial network, built in a simplified three-dimensional representation of tissue geometry, satisfies the statistical morphometric data on segment lengths, diameters and connectivities reported for real arterial networks. The model uses an avoidance algorithm to position successive vascular segments in the network. Assuming flows through the network to be steady, the calculated regional flow distributions showed (1) the degree of heterogeneity observed in normal hearts; (2) spatial self-similarity in local flows; (3) fractal spatial correlations, all with the same fractal dimension found in animal studies; (4) pressure distributions along the model arterial network comparable to those observed in nature, with maximal resistances in small vessels. In addition, the washout of intravascular tracer showed tails with power law slopes that fitted <i>h</i>(<i>t</i>) = <i>at</i><sup>–α–1</sup> with the exponents <i>α</i> = 2 for the reconstructed networks compared with those from experimental outflow concentration-time curves with <i>α</i> = 2.1 ± 0.3. Thus, we concluded that the fractal nature of spatial flow distribution in the heart, and of temporal intravascular washout, are explicable in terms of the morphometry of the coronary network.