PubMed Health⌕ Search

Biomedical subjects

A Tedgui

Publications and source records attributed to A Tedgui.

At least 127 records · Page 7Linked to original sources

[Adherence of monocytes to the aortic endothelium. Effect of the intraluminal pressure].

It is now generally accepted that most of the foam cells formed in the early fatty streak arise from circulating monocyte-macrophages. The effect of transmural pressure on mononuclear cells adherence to the vascular endothelium has been studied in excised rabbit thoracic aorta. Mononuclear cells were obtained from blood by centrifugation through lymphocyte separation medium (Ficoll-Paque, specific gravity 1.077). The mononuclear cell layer was collected from the interface and washed twice in RPMI containing 10 p. 100 fetal calf serum to remove contaminating platelets. The mononuclear cells were radiolabeled by incubation for 60 min in 0.1 mCi/ml of 51-chromium. After incubation, the cells were washed twice to remove free chromium, and resuspended in 5 ml RPMI containing 10 p. 100 fetal calf serum, at a concentration of 2 x 10(6) cells/ml. After ligature of intercostal arteries, 2 segments from the descending thoracic aorta were excised at in vivo length and under physiological pressure in order to preserve endothelial integrity. Arterial segments were incubated in oxygenated Krebs solution, at 39 degrees C and the intraluminal solution was changed to the solution containing the labeled mononuclear cells. The pressure was established at 70 mmHg in one segment and at 160 mmHg in the other. After 2 h incubation, the vessels were fixed under pressure. Each arterial segment was opened longitudinally and cut into 4 segments, which were laid on a microscopic slide and frozen at -20 degrees C. The surface area of each segment was measured and sections were cut en face at 20 micron intervals from the luminal surface to the adventitia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Function and structure of the vascular wall in experimental arterial hypertension. Effect of treatment].

The effects of converting enzyme inhibitor have been studied on the functions and structure of the arterial wall, and in both models of renovascular and spontaneously hypertensive rats. The arterial wall functions have been studied in terms of active vasomotricity, passive elasticity and transparietal convexion transport of proteins. Whatever the model used, hypertension was associated with significant changes in arterial wall functions: increase in smooth muscle cell tone, decrease in compliance, and decrease in transparietal filtration rate of proteins. These modifications could be reported to the increase in thickness of the media secondary to hypertrophy and hyperplasia of smooth muscle cell and to the increase in collagen network density. The effects of converting enzyme inhibitors on these phenomenons could depend on the experimental model used and the duration of treatment. In renovascular hypertensive animals, one month of treatment with perindopril normalized blood pressure and active compliance of the arterial wall. This functional benefit could be easily reported to the complete regression of the smooth muscle cell hypertrophy observed after treatment. By contrast, the increase in collagen network density was not regressed by treatment. By contrast, the increase in collagen network density was not regressed by treatment. By contrast, the increase in collagen network density was not regressed by treatment with trandolapril and thus the transparietal filtration rate of proteins remained decreased. In spontaneously hypertensive rats a perindopril treatment of long duration (3 months) partially regressed the functional change in compliance. This effect, once again, could be easily reported to the partial regression of medial hypertrophy which was associated, in this experimental condition, with a significant decrease in collagen network density.

Angiotensin-Converting Enzyme Inhibitors↗

Aortic 125I-albumin transport in patients with Marfan's syndrome and annuloaortic ectasia.

The morphologic, biochemical, and mechanical abnormalities of connective tissue fibrous proteins in Marfan's syndrome have been well studied, and their role in cardiovascular complications is well accepted. Less is known, however, about the state of the amorphous components of the aortic connective tissue. In the course of a study of transmural transport in blood vessels, we have had the opportunity to study dystrophic aorta from two young men who survived elective surgery; both with aortic insufficiency (AI) histologically compatible with Marfan's syndrome. One had recurrent chronic dissecting aneurysm (RCDA) as well. The aorta of the first (but not the second) was histologically compatible with Marfan's syndrome. Fresh specimens of intact ascending aorta were incubated in Krebs solution, pH 7.4, containing 125I-labelled bovine serum albumin for 2 h at 37 degrees C. The samples were then frozen, and serially sectioned in the plane of the lumenal surface. The radioactivity of the 20-micron thick sections was then determined, and expressed as a tissue/labelled solution concentration ratio. Transmural profiles of these ratios revealed no difference between the aorta of the RCDA patient with non-specific aortic dystrophy, and that of a 70-year-old man undergoing aortocoronary bypass. However, in the patient with aortic histology compatible with Marfan's syndrome, the average media concentration ratio was 5-fold less (4% vs. 20%).

Adult↗

Phasic coronary flow during aorto-caval fistula unclamping in dog.

The concomitant changes in components of external cardiac power and phasic coronary flow are described here in an aorto-caval fistula model (ACF) in the dog. Eleven animals were used in this study. The steady, oscillatory, and kinetic components of the external cardiac power and aortic impedance spectrum were calculated from the measurement of instantaneous flow and pressure in the ascending aorta. Arterial coronary flow was measured by a pulsed doppler flowmeter on the left anterior descending artery. The concomitant venous coronary flow was measured in the last two dogs. After unclamping of a large aorto caval fistula, mean blood pressure decreased from 96 +/- 31 mm Hg in the control state to 78 +/- 19 mm Hg 5 min after opening the shunt. Aortic blood flow and heart rate increased significantly. These changes in pressure and flow led to a decrease in the steady component of the external cardiac power (752 +/- 203 mW in the control state to 590 +/- 180 mW in the ACF; P less than 0.01), whereas the oscillatory and the kinetic components of the total external power increased (23.5 +/- 11 mW in the control state to 33 +/- 6 mW in the ACF for oscillatory power; 11.7 +/- 5.1 mW in the control state to 17.7 +/- 8.5 mW in the ACF for kinetic power, P less than 0.05). This increase in the oscillatory component of the cardiac power corresponded to the increase in the characteristic impedance of the aorta in the ACF (2,507 +/- 231 dyn.sec.cm-5 in the control state versus 4,366 +/- 745 dyn.sec.cm-5 in the ACF). These results suggested poor energetic efficiency in the matching between the left ventricle and the large arteries in this model. After unclamping the fistula, the systolic component of arterial coronary inflow becomes biphasic with a constant reverse flow from the myocardium to the aorta. The diastolic part of coronary arterial inflow decreased markedly, secondary to the decrease in perfusion pressure, and then reincreased to values near control values (59 +/- 22 ml/min in the control state versus 52 +/- 18 ml/min 5 min after unclamping the shunt). In five cases, the abrupt fall in blood pressure induced by unclamping the fistula led to a complete disappearance of diastolic coronary arterial inflow in diastoles of normal duration. The measured pressure of this zero inflow was about 30 mm Hg. During this zero coronary inflow, venous coronary outflow decreased but never disappeared.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effect of pressure and intimal damage on 131I-albumin and [14C]sucrose spaces in aorta.

To measure the distribution volume for sucrose and albumin in the media of the rabbit thoracic aorta, we studied the uptake of tracers in vitro. In most cases the tracers were applied to both luminal and adventitial surfaces at the same concentration. When transmural convection was prevented by pressurization of the arteries with air, there was a decrease in sucrose space (19% at 70 mmHg and 28% at 180 mmHg) and in albumin space (60% at 70 mmHg and 66% at 180 mmHg), compared with the respective spaces in relaxed arteries (0.42 for sucrose and 0.08 for albumin). Much smaller changes were found when intact vessels were pressurized with liquid (insignificant for sucrose, decreases of 24% at 70 mmHg and 14% at 180 mmHg for albumin). Removal of the endothelium, which increases transmural fluid flux, increased the space for sucrose (not significantly at 70 mmHg and 17% at 180 mmHg) and particularly for albumin (100% at 70 mmHg and 250% at 180 mmHg). We conclude that the interstitial volume and consequently the protein space within the media can be modified both by distending stresses applied to the vessel and by transmural fluid flux.

Albumins↗

Transmural gradient of tissue gas tensions in the canine left ventricular myocardium during coronary clamping and reactive hyperemia.

Mass spectrometry was used for the continuous, simultaneous and quantitative measurement of oxygen (PO2) and carbon dioxide (PCO2) partial pressures in the subendocardial and subepicardial layers of the left ventricle in 11 anaesthetized ventilated dogs. Under control conditions, PO2 was significantly lower in the subendocardium (13.5 +/- 4.5 mm Hg) than in the subepicardium (20.7 +/- 2.3 mm Hg), whereas PCO2 did not differ significantly (43 +/- 8.8 and 51 +/- 9.2 mm Hg respectively). These variables were not correlated with blood pressure or coronary blood flow. Subendocardial and subepicardial PO2 decreased less than 5 s after coronary occlusion. These changes were more rapid and severe in the subendocardium. After occlusion for 90 s: subendocardial PO2 was 4.1 +/- 6.3 mm Hg while subepicardial PO2 was 6.7 +/- 15.0 mm Hg (P less than 0.05). PCO2 reached peak values of 56 +/- 25 mm Hg subendocardial and 82 +/- 22 mm Hg subepicardial at 2.67 +/- 0.71 min and 3.43 +/- 0.93 min after coronary clamping. A reactive hyperemia occurred after coronary unclamping with different time courses and amplitudes for systolic and diastolic stroke flows while PO2 recovered with different kinetics. Subendocardial PO2 increased with a lower initial slope, probably in relation with the delay in the diastolic hyperemia. The observed delayed subendocardial hyperoxia, unrelated to the hyperemia, may indicate a delay in the recovery of normal work and metabolism in the inner layers of the myocardium.

Animals↗

A mechanical model of the dynamics of the coronary circulation in dog.

A mechanical model of the coronary circulation, including a capacitive extramyocardial compartment and a collapsible intramyocardial vascular bed has been described. The phasic coronary blood flow (CBF) in the circumflex artery of 11 anesthetized open chest dogs was studied in control conditions and during thoracic aortic constriction and arteriovenous fistula (AVF). We measured pressures in aortic and left ventricle, phasic CBF by pulsed Doppler flowmetry and in three dogs, pressure in the left anterior descending coronary artery. After aortic and AVF unclamping, we observed a major reverse flow in the circumflex artery. This reverse flow may be explained by the displacement of the collapse point of the intramyocardial compartment, due to the relative distribution of the intramyocardial tissue pressure and the intravascular coronary pressure. The specific role of the epicardial capacitive coronary compartment and of the intramyocardial pump action has been illustrated during coronary artery clamping, ectopic beats and changes in myocardial contractility. Under all the experimental conditions, the reported results demonstrated the ability of the model to describe the patterns of the dynamic of the coronary circulation.

Animals↗

The interaction of convection and diffusion in the transport of 131I-albumin within the media of the rabbit thoracic aorta.

The interaction of convection and diffusion in the transport of 131I-labeled albumin within the wall of rabbit thoracic aorta was studied in vessels excised at in vivo length. They were pressurized with a solution containing no tracer and immersed in a solution containing labeled albumin. The label then entered the wall tissue via the adventitia and had to diffuse against the convective flux which occurred from the lumen to the adventitia. Experiments were performed on intact and deendothelialized vessels pressurized to 70 and 180 mm Hg. At the end of each experiment the vessels were subjected to sequential frozen sectioning parallel to the lumenal surface. The radioactivity of the 20-micron-thick sections was determined and expressed as a tissue:labeled solution concentration ratio. Transmural profiles of these ratios were thus obtained. The steady state was found to be achieved by about 90 minutes. When the convection was enhanced by removal of the endothelium, the average ratios were lower than when the endothelium was intact, and the profile was much flatter. The results suggest that convection influenced macromolecular transport within the arterial wall, even in vessels with intact endothelium.

Animals↗

Effect of descending thoracic aorta clamping and unclamping on phasic coronary blood flow.

Myocardial infarctions during aortic surgery often occur after aortic clamping and unclamping. In order to investigate the aortic blood pressure (AoBP)-coronary blood flow (CBF) relationship, hemodynamic parameters and phasic circumflex CBF in 15 anesthetized and open-chest dogs during clamping and unclamping of the thoracic descending aorta have been recorded. During clamping, mean aortic blood pressure (MAoBP) rose from 97 + 17 to 150 + 42 mm Hg (P less than 0.001), and total combined left-ventricular power (Wtc) from 692 + 232 to 923 + 402 mW (P less than 0.001) while the ascending aortic blood flow (AoBF) and heart rate did not change significantly. The mean circumflex blood flow (MCBF) increased from 67 + 30 to 88 + 30 ml/min. The increase in systolic coronary blood flow (+73%) was larger than that in diastolic coronary blood flow (DCBF) (19%). The late coronary resistances were increased 39%. Conversely, after unclamping, MAoBP decreased while AoBF and Wtc increased. During the first cardiac cycles after aortic unclamping DCBF decreased 50% with a decrease in the diastolic blood pressure (DBP). Four cycles later, DCBF reincreased while DBP kept on decreasing. This may be related to an active coronary vasodilatation. A linear relationship between DCBF and DBP has been obtained during acute change in DBP due to clamping or unclamping. From these linear relationships, the change in diastolic zero flow pressure (PfO) has been found to be about + 40 mm Hg during clamping. This change in PfO may be responsible for the observed large fall in DCBF during unclamping. The decrease in DCBF associated with the increase in Wtc accounts for the delayed active vasodilatation.

Animals↗

Filtration through damaged and undamaged rabbit thoracic aorta.

The influence of luminal pressure and endothelial removal on fluid filtration across the arterial wall has been studied in the rabbit thoracic aorta. Segments of aorta were excised in such a way as to prevent shortening and depressurization and were filled with a 4% albumin-Tyrode solution. Experiments were carried out at two controlled pressure levels (70 and 180 mmHg). The hydraulic conductivity (Lp) of the total wall, calculated from the filtration data, was 4.00 +/- 1.31 and 2.44 +/- 0.80 (SD) X 10(-8) cm/(s X mmHg) in intact wall at 70 and 180 mmHg, respectively (P less than 0.01), whereas values for deendothelialized arteries were higher (P less than 0.01), being 5.36 +/- 1.62 and 5.27 +/- 0.84, respectively. The apparent pressure dependence of conductivity of the intact wall may be due to altered strain of the interstitial matrix. Removal of the endothelium can increase the hydration and porosity of the medial interstitium but, assuming that the conductivity of the deendothelialized wall at 70 mmHg is the same as that of the normal media, the calculated conductivity of the endothelium is 15.76 X 10(-8) cm/(s . mmHg).

Animals↗

Study of relations between arterial oscillation period and heart rate.

This study was performed to determine the relationship between variations of arterial cross-section and cardiac period. Relative section variations were recorded by impedance rheography. In 176 anesthetized adult mongrel dogs, aortic and femoral rheograms, femoral pressure, and ECG were recorded. The cardiac period (Tc) and the interval between the systolic and the dicrotic wave, i.e., the arterial intrinsic period (Ta), were measured and related to each other (Tc/Ta ratio). In 125 dogs, the dicrotic wave appeared spontaneously. In these cases Tc/Ta 1.98 +/- 0.16. In 51 dogs, no dicrotic wave appeared spontaneously. Lengthening of cardiac period was obtained in 25 of these dogs by vagus stimulation. As related to the cardiac period before vagal stimulation Tc/Ta was then 0.98 +/- 0.08. In the remaining 26 dogs, such a lengthening was obtained by inducing a premature ventricular depolarization. In this group, Tc/Ta was 1.00 +/- 0.03. The results of the present study suggest that a constant adaptation exists between ventricular ejection and arterial dynamics. The physiologic implications are discussed.

Animals↗

Effect of vasopressin on phasic coronary blood flow.

The effects of vasopressin on the coronary circulation have been studied with regard to its general hemodynamic effects. Aortic blood pressure (BP), left ventricular pressure (LVP), aortic blood flow (AoBF), and circumflex blood flow (CBF), were measured in 12 open-chest dogs, under control conditions and during vasopressin infusion (25 mU/kg/min). During vasopressin infusion, the mean aortic blood pressure (MBP) was increased from 104 +/- 23 mm Hg to 161 +/- 23 mm diastolic blood pressure (DBP) was more increased (+55%) than the systolic blood pressure (SBP) (+40%). AoBF was decreased from 2.169 +/- 0.408 l/min to 1.118 +/- 0.303 l/min; and the heart rate was decreased by 18%. The total combined left ventricular power did not change significantly. The increase in total peripheral resistance (TPR) (+200%) was the main change in impedance spectrum. The mean circumflex coronary blood flow (MCBF) was decreased from 48 +/- 8.6 ml/min to 33.4 +/- 9.7 ml/min. This decrease was more important in the diastolic circumflex blood flow (DCBF) (-33%) than in the systolic one (-0.8%). The diastolic pressure time index (DPTI) was more increased than the systolic pressure time index (SPTI). The DPTI/SPTI ratio was increased from 0.91 to 1.3. Long diastoles, induced by vagus nerve stimulation, have permitted to characterise the relationship between pressure and coronary blood flow during diastole. This relationship was linear under basal condition, and during vasopressin perfusion. This made it possible to determine the critical closing pressure (Pf0), and the coronary conductance (the slope of the regression curve). Vasopressin induced an increase in Pf0, from 33.7 +/- 95 to 77.4 +/- 16.07 mm Hg (p less than 0.001), and a decrease in coronary conductance, from 0.8 +/- 0.32 to 0.5 +/- 0.1 ml/min/mm Hg. The effect of an acute change in perfusion pressure on the coronary flow, under control conditions and during vasopressin infusion was studied by opening a large arteriovenous fistula. Unclamping of the fistula, under control conditions, allowed to realize an acute fall in DBP from 82.5 +/- 6.36 to 35.5 +/- 9.19 mm Hg, and in DCBF, from 58.5 +/- 9.2 to 20 +/- 9.8 ml/min. During vasopressin infusion, a similar fall in perfusion pressure lead to a zero diastolic circumflex blood flow, for a diastolic aortic blood pressure of 56 +/- 12 mm Hg. However, vasopressin did not affect the delayed active coronary vasodilatation.

Animals↗

Non-invasive ultrasonic cardiac output measurement in intensive care unit.

A non-invasive method for measuring cardiac output utilizing M-mode echography and pulsed Doppler ultrasound is described. Measurements were obtained in 26 of 29 randomly selected, mechanically ventilated patients. These values were compared with simultaneously measured cardiac outputs by thermodilution. There was a statistically significant linear relationship between Cardiac Output measured by Doppler (DCO) and Thermodilution (TDCO): DCO = 0.86 TDCO + 0.29 l/min (r = 0.96, n = 26, SEE = 0.45 l/min) over the range of 1.75-8.5 l/min. DCO had the additional advantage of measuring peak flow velocity and maximal blood flow acceleration during early systole, indices of left ventricular pumping ability. Ultrasonic monitoring of cardiac output may be an important supplement to invasive methods in critical care.

Adult↗

Can statins reduce the inflammatory response to cardiopulmonary bypass? A clinical study.

OBJECTIVE: In addition to lowering lipid levels, statins might reduce leukocyte-endothelial cell interactions. Therefore, we assessed whether this effect could limit the inflammatory response to cardiopulmonary bypass (CPB) in cardiac surgical patients. METHODS: Twenty patients undergoing valve or coronary operations with tepid (34 degrees C) CPB were randomized to receive an oral dose of atorvastatin (40 mg the evening before and 40 mg the morning of surgery) or to serve as controls. Pre- and post-CPB blood samples were assayed for neutrophil CD11b surface adhesion molecule and oxidative burst. Plasma levels of interleukins 6 and 8, P-selectin, soluble intercellular adhesion molecule-1, and lactoferrin were measured by enzyme-linked immunosorbent assay (ELISA). In addition, right atrial biopsies were taken before and at the end of CPB, and processed for the expression of the transcription nuclear factor-kappa B (NF-kappaB). RESULTS: The two groups did not differ with regard to pre- and intraoperative data. Except for P-selectin, postbypass values of all markers significantly increased over baseline values, but atorvastatin therapy failed to attenuate the magnitude of this increase. In the two groups, the expression of NF-kappaB significantly (p = 0.004) increased over baseline without group effect. Postoperative clinical outcomes did not differ either between the two groups. CONCLUSION: These data show that acute preoperative statin therapy fails to limit the inflammatory response to CPB; however, the data also document a major upregulation of NF-kappaB during cardiac operations, thereby providing a sound rationale for interventions targeted at inactivating this key component of the inflammatory cascade.

Aged↗

Rapid effect of LPS-activated macrophages on the reactivity of the rat mesenteric artery.

This study was designed to evaluate the effects of lipopolysaccharide (LPS)-activated macrophages in the perfused mesenteric circulation of the rat. The mesenteric network of anesthetized rats was perfused in situ under constant flow conditions and the diameter and pressure of the mesenteric artery were continuously recorded. For the first 30 min the mesenteric network was perfused with an RPMI solution (control condition); thereafter it was perfused for 60 min with the same solution containing either (1) LPS (1 microgram/ml), (2) elicited macrophages (10(6) cells/ml), (3) LPS-activated macrophages or (4) supernatants derived from LPS-activated macrophages (SPN). The changes in arterial diameter induced by topical application of phenylephrine (PE, 10 mumol/l) were measured under control conditions and then 30 and 60 min after the onset of perfusions. The intravascular pressure was similarly increased (51 +/- 6%, p < 0.001) by the perfusion of activated macrophages or elicited macrophages but was not affected by perfusion of LPS or SPN. Despite the same level of transmural mesenteric pressure in rats perfused with activated and elicited macrophages, the mesenteric diameter was significantly larger with activated than with elicited macrophages (p < 0.05). Under control conditions, PE induced a marked decrease in arterial diameter from 495 +/- 15 to 265 +/- 13 microns (p < 0.001). Perfusion of LPS, elicited macrophages or SPN did not modify the vascular reactivity to PE. Perfusion of activated macrophages reduced the PE-induced contraction by 77 +/- 6% (p < 0.001). Perfusion of elicited macrophages with a nitric oxide (NO) donor (SIN-1, 10 mumol/l) reproduced the effect of LPS-activated macrophages while addition of an NO scavenger (oxyhemoglobin, 10 mumol/l) prevented the depression of the vascular reactivity to PE by activated macrophages. Finally, activated macrophages preincubated with an inhibitor of NO synthesis (NG-monomethyl-L-arginine); L-NMMA), and then perfused in RPMI solution without L-NMMA had no effect on the PE reactivity of the mesenteric artery suggesting that NO released by activated macrophages directly and rapidly inhibited the contractility of the mesenteric artery. The results of this study demonstrate the opposing effects of macrophages in the mesenteric circulation to increase microvascular resistance by a rheological effect while decreasing the reactivity of the mesenteric artery as a result of NO released by macrophages.

Animals↗

Reduction of transmural 125I-albumin concentration in rat aortic media by chronic hypertension.

Relative 125I-albumin concentration was measured in vivo in the aortic media of sham-operated (n = 10) and hypertensive (two-kidney, one clip) rats, untreated (n = 8) or treated (n = 10) by an angiotensin converting enzyme inhibitor (CEI, Trandolapril). Blood pressure was acutely lowered to a normal level at the time of the experiment in hypertensive rats (n = 7) to separate the direct effect of increased pressure from the effect of pressure-induced structural changes. Relative tissue concentration profiles of labeled albumin across the media were obtained using a serial frozen-sectioning technique. In hypertensive rats, the mean medial albumin concentration decreased by 35% in the ascending arch and 32% in the descending arch (p less than 0.01). When blood pressure was acutely lowered in hypertensive animals, this value decreased further by 56% in the ascending arch, 48% in the descending arch (p less than 0.01), and 22% in the thoracic aorta (p less than 0.05) as compared with controls. The medial thickness in hypertensive rats was significantly increased (more in the ascending arch than in the rest of the aorta). Four-week CEI treatment reversed hypertension and medial thickening, but the mean medial albumin concentration remained significantly lower in the arch (by 36% in the ascending part and 40% in the descending part, p less than 0.01). The collagen content in the thoracic aorta was significantly increased in hypertensive rats (by 40%, p less than 0.01) and remained increased (by 29%, p less than 0.01) after CEI treatment. These results suggested that the hypertension-induced structural changes might reduce the medial distribution volume for albumin, whereas elevated blood pressure per se tended to enhance albumin concentration within the media. However, the net result of chronic hypertension was a reduction of the mean medial albumin concentration. The aortic arch appeared to be more affected than the rest of the aorta. Fiber content, more than medial thickness, might be responsible for the observed differences in albumin concentration. Lowering of blood pressure seemed to be insufficient to restore normal albumin concentration profiles and perhaps those of other macromolecules. This finding may be relevant in evaluating some of the complications associated with hypertension.

Albumins↗

Effect of nicardipine and verapamil on in vitro albumin transport in rabbit thoracic aorta.

Calcium antagonists have been shown to have an antiatherogenic effect. We investigated the effect of nicardipine and verapamil on the albumin transport across the media of excised rabbit thoracic aorta. The effect of nicardipine was also tested in deendothelialized arteries. The vessels were incubated for 90 minutes in oxygenated Krebs or 80 mM KCl solutions at in vivo length and at a transmural pressure of 70 mm Hg. The transmural concentration profiles of 125I-albumin across the media were measured by a frozen serial sectioning technique. In deendothelialized arteries, K+ decreased the mean medial uptake of labeled albumin, whereas 10(-7) M nicardipine in Krebs increased the uptake and 10(-9) M nicardipine had no effect. In a K+-rich solution, containing 10(-7) or 10(-9) M nicardipine, the medial uptake was lower than, but not significantly different from, that in Krebs. In intact K+-treated vessels, the wall concentrations near the lumen were increased and concentration gradients across the media were observed, possibly due to an increase in endothelial permeability following K+-induced contraction of the endothelial cells. This effect was reversed by the addition of 10(-7) M nicardipine, but not by 10(-7) M verapamil. Nicardipine and verapamil (10(-7) M) in Krebs solution enhanced the albumin uptake by the media of intact arteries. This effect on the permeability of the media may be related to the antiatherogenic effect of calcium antagonists.

Animals↗

Oncostatin M induces interleukin-6 and cyclooxygenase-2 expression in human vascular smooth muscle cells : synergy with interleukin-1beta.

Oncostatin M (OSM), a cytokine first identified from activated monocytes and T lymphocytes, is one of the most potent autocrine growth factor for AIDS and Kaposi's sarcoma. Little is known about the effects of OSM on normal vascular cells. We thus exposed human aortic smooth muscle cells (hASMCs) to OSM, examined cell proliferation and morphology, and determined interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) expression. OSM had a weak antiproliferative effect. After a 4-day incubation with 100 ng/mL OSM, cell count decreased to 69+/-3% of control. However, OSM induced striking changes in hASMC morphology, characterized by a polyclonal shape, in contrast to the spindle morphological feature of control hASMCs. OSM stimulated the release of IL-6 by hASMCs in a dose-dependent way; after a 48-hour exposure, values were 8.5+/-0.7, 29.7+/-3.5, 50.9+/-4.4, and 73.8+/-7.6x10(3) U/mL (n=6) at OSM concentrations of 0, 1, 10, and 100 ng/mL, respectively. OSM induced marked expression of COX-2 protein and mRNA. Leukemia inhibitory factor had no effect on hASMCs, indicating that OSM effects on hASMCs were mediated by the OSM type II receptor and not by the leukemia inhibitory factor receptor. OSM used the JAK/STAT signaling pathway, as demonstrated by rapid phosphorylation of JAK1 and specific activation of STAT1. Interestingly, OSM acted in synergy with IL-1beta on IL-6 production and COX-2 expression. In conclusion, OSM is a novel regulator of human smooth muscle cell functions, acting in concert with IL-1beta, and OSM may play a role in major vascular diseases such as atherosclerosis.

Cells, Cultured↗