摘要:

Introduction:Angiotensin converting enzyme (ACE) inhibitors have a beneficial effect on glomerular injury in different models of renal damage. Their presumed nephroprotective action has been related partly to actions on glomerular growth. We examined the effect of prophylactic administration of a moderate dose of enalapril (50 mg/l in drinking water) in male Sprague-Dawley rats on a diet containing 40% protein and moderate NaCI.Methods:The rats were followed for 8 weeks after subtotal nephrectomy and compared with sham-operated matched controls.ResultsThe number of glomeruli per kidney was reduced significantly in both the enalapril-treated and control groups. The median glomerulosclerosis index was significantly lower in the enalapril-treated than in the untreated subtotally nephrectomized rats. The mean absolute glomerular volume was significantly higher after subtotal nephrectomy, but was significantly lower in the enalapril-treated than in the untreated subtotally nephrectomized rats. The total numbers of cells per glomerulus and of mesangial or endothelial cells, as well as nuclear volumes of mesangial cells and the total capillary length per glomerulus, were all significantly higher after subtotal nephrectomy. These parameters were significantly lower in the enalapril-treated than in the untreated nephrectomized rats. The rise in systemic blood pressure was modest in the nephrectomized rats and the arteriolar volume: length ratio was unchanged by treatment with enalapril.Conclusions:In subtotally nephrectomized rats enalapril inhibits (but fails to reverse completely) the compensatory glomerular enlargement and the increase in mesangial cell number and activation, with a concomitant reduction in the development of glomerulosclerosis. The result is compatible with antiproliferative, and possibly antiangiogenic, actions of ACE inhibitors.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:Endothelin is thought to be related to cardiovascular disease. The purpose of this study was to determine whether endothelin levels could be reduced by a calcium antagonist and a 'natural factor'.Design:Since calcium ionophores can induce endothelin-1 messenger RNA synthesis in cultured endothelial cells, the calcium antagonist nisoldipine was used in this study to determine whether it could reduce endothelin levels. It has been reported that coculture of endothelial cells and smooth muscle cells from different species and different parts of the body can reduce endothelin levels. This study was also designed to determine whether coculture of the two cell types from the same species and the same section of an artery could reduce endothelin levels.Methods:Cultured endothelial cells from human umbilical artery (HUAEC) and umbilical vein (HUVEC) were treated with increasing concentrations of nisoldipine. HUAEC were cocultured with human umbilical artery smooth muscle cells (HUASMC). Endothelin levels were measured by a radioimmunoassay.Results:Incubation of the HUAEC with nisoldipine for either 7 or 24 h resulted in a dose-dependent (10-810-5mol/l) reduction in endothelin levels in the conditioned media. Endothelin levels in cell lysates were not detectable in either the absence or the presence of nisoldipine. This suggests that the reduction of endothelin levels in the media could be due to inhibition of endothelin synthesis. Under the same conditions, incubation of HUVEC with the same concentrations of nisoldipine produced a similar concentration-dependent reduction in endothelin levels. Endothelin levels were undetectable in the conditioned media from HUASMC. Coculture of HUAEC with HUASMC significantly reduced endothelin levels (P<0.01) compared with HUAEC cultured alone.Conclusions:Endothelin levels can be reduced by the calcium antagonist nisoldipine and a 'natural factor' associated with smooth muscle cells.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:It has been postulated that vasoconstrictors cause insulin resistance. This effect has been documented for epinephrine but not for angiotensin II (Ang II). The aim of this study was to investigate the effect of the latter on insulin sensitivity.Design:In order to study the influence of subpressor doses of Ang II on insulin-mediated glucose uptake under euglycemic conditions, eight healthy volunteers were allocated in random order to sham infusion or infusion of Ang II (first 0.75 ng/kg per min and subsequently 1.5 ng/kg per min). In addition, in seven of the subjects Ang II was infused after 3 days of indomethacin pretreatment (150mg/day).Methods:Insulin-mediated glucose uptake (expressed as M value) was measured with the euglycemic clamp technique. Insulin levels were measured enzymatically, plasma renin activity, Ang II, aldosterone and C-peptide levels by radioimmunoassay, blood pressure by Dinamap and muscle blood flow by plethysmography.Results:The M value after sham infusion was 7.81 ± 1.52mg/kg per min and after 1.5 ng/kg Ang II per min was 9.76 ± 1.26mg/kg per min (P<0.001). Indomethacin pretreatment did not abolish the Ang ll-induced rise in the M value. Mean arterial blood pressure during the euglycemic clamp was unchanged with sham infusion and the low dose of Ang II. It increased slightly with the higher dose of Ang II. Inferior limb muscle perfusion was higher after infusion of Ang II than after sham infusion; this effect was not obliterated by indomethacin pretreatment.Conclusions:Ang II increases insulin-mediated glucose uptake: that is, it enhances insulin sensitivity by mechanisms independent of prostaglandins. The observations are of potential relevance to the changes in insulin sensitivity in some forms of hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To investigate the extent to which the immune system is influenced in patients with previous malignant hypertension.Design:Twenty-three patients with malignant hypertension (fundus hypertonicus grades III or IV) in the Gothenburg area were studied over a 3-year period. After treatment had been instituted they were investigated to establish the function of the cellular immune system (number of T lymphocytes and the proliferative response to T-cell mitogens), human leucocyte antigens A, B and C and frequency of autoantibodies.Methods:The numbers of T lymphocytes were quantified as erythrocyte rosettes. Lymphocyte-stimulation tests were carried out using the T-cell mitogens phytohaemagglutinin and concanavalin-A. Autoantibodies were determined with immunoassay techniques and leucocyte A, B and C antigens with a lymphocytotoxicity test.ResultsThe frequency of T lymphocytes and their baseline thymidine incorporation were significantly depressed in patients with previously malignant hypertension compared with control subjects. The group with malignant hypertension also had a decreased proliferative response to concanavalin-A but not to phytohaemagglutinin, and they had an increased frequency of antinuclear antibodies. Human leucocyte antigen B15 tended to occur more frequently in patients with malignant and non-malignant hypertension than in control subjects, especially if a family history of hypertension was taken into consideration.Conclusion:The results from the present study indicate that immune mechanisms are involved in malignant hypertension, either secondary to the vascular damage or as a primary abnormality.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:Alterations in platelet α2-adrenoceptor and mononuclear leucocyte β2-adrenoceptor characteristics in primary hypertension have been extensively studied. The results of the reports have not been consistent, possibly because of the small number of subjects in most of the studies. We therefore studied the blood-cell adrenoceptor characteristics in a relatively large group of primary hypertensive and normotensive subjects.Design:Platelet α2-adrenoceptor characteristics were compared in 65 hypertensive and 51 normotensive subjects. Mononuclear leucocyte β2-adrenoceptor characteristics were compared in 72 hypertensives and 67 normotensives. Untreated hypertensive subjects were selected from the outpatient clinic and the normotensive controls were recruited by a newspaper announcement.Methods:Platelets and mononuclear leucocytes were isolated from blood samples obtained after at least 10 min supine rest. The α2- and β2-adrenoceptor characteristics were determined with [3H]-rauwolscine and [125I]-(—)cyanopindolol, respectively. Correlations between the adrenoceptor characteristics and clinical parameters of the subjects were studied.Results:No differences in α2- or β2-adrenoceptor densities were observed between the two groups. However, a significantly lower equilibrium dissociation constant for [3H]-rauwolscine was observed in the hypertensive group. The correlations between the adrenoceptor characteristics and clinical parameters were weak and mostly not statistically significant. The results were compared with the most relevant studies in the literature.Conclusions:From our study and the literature, we conclude that blood-cell adrenoceptor characteristics are unchanged in primary hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID