ISSN:1018-1172    

DOI:10.1159/000159175

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Intimal accumulation of macrophages and changes in the phenotype and growth properties of vascular smooth muscle cells (SMCs) represent key events in the development of atherosclerotic lesions. Here we report on the in vivo effect exerted by nitrendipine on aortic tissue of cholesterol-fed rabbits. We have focused especially on the myosin heavy chain (MyHC) pattern expressed by aortic SMC, taken as a marker of cell differentiation. Using monoclonal antibodies specific to the different forms of MyHC, three differentiation steps were determined: adult, postnatal, and fetal. Nitrendipine administered in conjunction with a cholesterol-enriched diet reduced the development of atherosclerotic lesions (atherosclerosis index: 0.21 vs. 0.32 in untreated animals, p < 0.005), despite persistently high serum cholesterol levels. Compared to untreated controls, nitrendipine-treated animals displayed a decreased number of postnatal-type SMCs in the media underlying the plaque (prevalence index: 0.07 vs. 0.26, p < 0.0001 and a lower aortic cholesterol content (free cholesterol: 3.3 vs. 11.5 ng/mgp < 0.0001; esterified cholesterol: 7.2 vs. 40.5 ng/mg, p < 0.0001). Moreover, nitrendipine treatment decreased the intimal accumulation of macrophages and fetal-type SMCs. It is conceivable that calcium antagonists may exert their antiatherogenic effect, at least in part, through cellular changes unrelated to the classical risk factors.

ISSN:1018-1172    

DOI:10.1159/000159126

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The endothelial cell is unique because it must undergo a transition from a resting cell with a cytoskeleton organized for barrier function to one which promotes cell translocation following denuding endothelial injury. Since actin microfilaments are critical for both maintaining the integrity of the resting monolayer and for optimum reendothelialization, we carried out a detailed study of the organization of microfilaments as the cell undergoes the transition from a resting to a translocating cell. We used an in vitro model in which a linear wound was made in a confluent monolayer of porcine aortic endothelial cells. The complex reorganization of actin microfilament bundles following injury and their relationship to microtubules and vinculin was studied in cells at the wound edge using immunofluorescent scanning laser confocal microscopy and time-lapse videomicroscopy. In the resting confluent monolayer, microfilaments were present as a dense peripheral band (DPB) located toward the upper part of the cell and as central microfilament bundles at the substratum. Three distinct stages of microfilament reorganization occurred sequentially during early repair. Stage 1 followed wounding and involved the reduction of the DPBs of microfilaments and associated peripheral cell-cell vinculin plaques. This was associated with rapid forward actin-based lamellipodia extrusions and cell elongation. Low-dose cytochalasin, which did not disrupt the morphology of microfilament bundles, reduced elongation. Stage 2 was characterized by central microfilaments behind the lamellipodia distributed parallel to the wound edge with vinculin plaques at their tips. This was associated with prominent spreading at the front of the cell which enhanced the extent of coverage of the denuded wound area. Stage 3 was characterized by the orientation of central microfilaments perpendicular to the wound edge with vinculin plaques at their tips and was associated with the initiation of cell translocation. There was no specific structural association between central microfilaments and microtubules as the former were toward the substratum while the latter were toward the center and upper part of the cell. Thus, the sequential appearance of the three patterns of microfilament distribution define the cytoskeletal events that regulate the reestablishment of endothelial integrity following denuding endothelial injury.

ISSN:1018-1172    

DOI:10.1159/000159127

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1018-1172    

DOI:10.1159/000317468

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Single cells were freshly isolated from human omental resistance arteries using an enzymatic dispersion technique. Calcium channel currents (IBa) were recorded using whole cell voltage clamp techniques with Ba2+ as the charge carrier. BHT 933, a selective α2-adrenoceptor agonist, increased IBa. The effect of BHT 933 was reversible following washout. The action of BHT 933 was blocked by yohimbine. Pretreatment of tissues with pertussis toxin for 18 h or inclusion of GDP-β-S in the intracellular patch pipette solution also prevented the BHT 933-induced rise in IBa, but had no effect on IBa in the absence of BHT 933. Activation of α2-adrenoceptors in human vascular smooth muscle cells increases IBa by a mechanism involving a pertussis toxin-sensitive G prote

ISSN:1018-1172    

DOI:10.1159/000159128

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1018-1172    

DOI:10.1159/000317469

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The role of L-type voltage-operated Ca2+ channels (VOCs) in myogenic responsiveness was studied in cannulated rat mesenteric small arteries [mean diameter at 100 mm Hg and full dilation was 329 ± 9 (SE) µm]. Twenty-six arteries were cannulated and pressurized. The luminal cross-sectional area of these vessels was monitored continuously. To test for myogenic responsiveness, pressure was raised stepwise from 20 to 60 and from 60 to 100 mm Hg. Pressure elevation enhanced the vascular tone, reflecting spontaneous myogenic responsiveness. Nifedipine (1 and 10 µM) suppressed spontaneous myogenic responses. The αi-adrenoceptor agonist phenylephrine (1 and 10 µM), when administered at 20 mm Hg, elicited constriction and vasomotion, and potentiated myogenic constriction to subsequent pressure elevation. Nifedipine (1 and 10 µM) also suppressed phenylephrine-potentiated myogenic responsiveness. Stimulation of VOCs with BAY K 8644 (10-300 mM) had no effect at 20 mm Hg, but augmented myogenic responsiveness. K+ (16-46 mM) caused concentration-dependent constrictions when administered at 20 mm Hg, and potentiated myogenic responsiveness when the pressure was raised from 20 to 60 mm Hg. Thus, any intervention that blocked the VOCs also blocked myogenic responses, and any form of stimulation of the VOCs also augmented myogenic responses. Therefore, we conclude that VOCs are essential for the myogenic responsiveness of cannulated rat mesenteric small art

ISSN:1018-1172    

DOI:10.1159/000159129

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1018-1172    

DOI:10.1159/000317470

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Proliferation and migration of vascular smooth-muscle cells (VSMCs) are essential events in neointimal hyperplasia. Recent findings that active oxygen species induce pro-oncogene expression, and stimulate VSMC DNA synthesis and cell division, suggest that active oxygen species may play an important role in intimal proliferation after arterial injury. To determine how the redox state of the artery was altered by injury, the levels of thiobarbituric-acid-reactive substances (TBARs, markers of lipid oxidation) and glutathione peroxidase (GSH-PX, the enzyme responsible for the production of glutathione, a major intracellular antioxidant) were measured in the rat aorta after balloon injury. There was an inverse relationship between the level of TBARs, which increased significantly to a maximum 17% greater than normal at 10 days after injury (p < 0.05, n = 7), and the activity of GSH-PX, which decreased significantly to a minimum 36.5% less than normal at 10 days after injury (p < 0.05, n = 7). To determine whether maintaining a more reduced vessel environment would inhibit intimal proliferation, L-cysteine was administered by intraperitoneal injection from 3 days before to 14 days after balloon injury. At 14 days after the arterial injury, the aorta was harvested for histological and morphometric measurements of TBARs and GSH-PX. At 7 and 14 days after balloon injury, the aorta was harvested for [3H]thymidine incorporation studies. Efficacy of therapy was demonstrated by a significant decrease in the level of TBARs and an increase in the activity of GSH-PX (p < 0.05 vs. the control group, n = 7). In the L-cysteine group, all parameters of intimal proliferation were significantly reduced compared to the controls, including the intima:me-dia ratio (0.091 vs. 0.253, p < 0.05); the cross-sectional area of the neointima (0.0563 compared to 0.140 mm2, p < 0.05), coverage of the internal elastic lamina by the neointima (23.44 compared to 43.27%, p < 0.05), and [3H]thymidine incorporation (at 7 days 240.58 vs. 350.68 cpm/mg tissue, p < 0.05; at 14 days 181.71 vs. 275.30 cpm/mg tissue, p < 0.05). These results demonstrate dynamic alterations in the vessel redox state after arterial injury, and suggest that maintaining a more reduced environment (e.g. administration of L-cysteine) will reduce intimal proliferation after arterial injury.

ISSN:1018-1172    

DOI:10.1159/000159130

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

In a previous study we have shown that the wall of the elastic carotid artery bifurcation (CAB) stiffens inhomogeneously with increasing age, the carotid artery bulb being most affected. In the present study the effect of ageing on the elastic properties of the wall and the strain the wall is exposed to along the muscular femoral artery bifurcation (FAB) was investigated using the CAB for comparison. The study was performed with 10 young (aged 20-30 years) and 10 old (50-60 years) presumed healthy volunteers. Distensibility along the bifurcation was determined by measuring noninvasively the maximum relative diameter changes of the artery during systole (peak △d/d · 100%), which is also a measure of strain, at various sites along both bifurcations by means of a vessel wall moving detector system. This system also makes the assessment of (end-diastolic) diameter possible. At all levels along the CAB, the diameter was significantly larger in the old than in the young. In the FAB, the diameter was only significantly larger in the old than in the young in the common and superficial femoral arteries. At all levels in the CAB, peak △d/d·100% was significantly lower in the old than in the young, the carotid artery bulb being more affected than the common carotid artery (CCA), while in the FAB this parameter was lower in the old than in the young only in the common femoral artery (CFA). Peak △d/d· 100% was similar in the CCA and in the bulb in the young, but significantly higher in the CCA than at all levels in the bulb in the old. In the FAB, in the young peak △d/d · 100% was significantly higher in the CFA than at both levels in the deep and superficial femoral arteries, while in the old no significant differences in peak △d/d · 100% along the FAB could be detected. These findings indicate that the loss of wall elasticity with increasing age is different in the muscular and elastic arterial bifurcations investigated. The homogeneous distribution of wall elasticity in the elastic CAB at a younger age becomes inhomogeneous at an older age, while the opposite is observed in the muscular FAB. The changes in strain the different parts of the bifurcations are exposed to with increasing age are different in the CAB and the FAB. Differences in distensibility along bifurcations will make them deform inhomogeneously during the

ISSN:1018-1172    

DOI:10.1159/000159131

出版商:S. Karger AG    

年代:1996

数据来源: Karger