Renin-angiotensin blockade lowers MCP-1 expression in dia-to precede the earliest manifestations of diabetic betic rats.nephropathy [1][2][3]. In rats made diabetic with streptozo-Background. Glomerular macrophage accumulation in diatocin (STZ) and maintained at moderate levels of hyperbetes implicates monocyte recruitment mechanisms in the glycemia by daily insulin injections, glomerular hyperpathogenesis of diabetic nephropathy. To test the hypothesis filtration, caused by elevations of glomerular perfusion that overexpression of monocyte chemoattractant protein-1 (MCP-1), a monocyte chemoattractant, is attenuated by reninand intracapillary hydraulic pressure (glomerular capilangiotensin system (RAS) inhibition, we assessed expression lary hypertension), likewise presages glomerular injury of genes regulating monocyte transmigration in the glomeruli [4]. Both glomerular capillary hypertension and the subof diabetic rats. sequent development of glomerular injury are dependent Methods. Competitive reverse transcription-polymerase chain on an intact renin-angiotensin system (RAS), as revealed reaction (RT-PCR) was used to semiquantitate mRNA expression in glomeruli harvested by sieving at serial intervals after by earlier studies from this laboratory showing that treatthe induction of diabetes by streptozotocin in Munich-Wistar ment with angiotensin-converting enzyme inhibitors rats. Although subject to limitations, competitive RT-PCR pro-(ACEIs) [5], alleviated glomerular capillary hypertenvides an objective measure suited to the minute quantities of sion and prevented the development of diabetic ne-RNA extractable from glomerular isolates. Results. Time-dependent elevation of MCP-1 expression phropathy in STZ rats, independent of glycemic control. was dramatically suppressed by treatment with the angiotensin-These studies established the experimental basis for the converting enzyme inhibitor enalapril or the AT1 receptor antagfirst successful large-scale clinical trial of ACEI in type onist candesartan, and was closely associated with effects on I diabetic patients [6]. proteinuria and glomerular macrophage number. By contrast, Glomerular injury occurring in the context of angiono sustained suppression of the cell adhesion molecules intercellular adhesion molecule-1 or vascular cell adhesion moletensin-dependent processes, including augmented glocule-1 or the classic MCP-1 stimulators tumor necrosis factor-␣ merular hemodynamics, may involve mononuclear cells or interleukin-1 followed RAS inhibition, and suppression of and an array of cytokines and other proinflammatory transforming growth factor-1 expression was transient. molecules. Evidence is accumulating that supports theConclusion. These data suggest that glomerular macrophage recruitment in experimental diabetes is largely determined by hypothesis that macrophages and macrophage products angiotensin-stimulated MCP-1 expression. We conclude that play a significant role not only in inflammatory glomeruthe RAS is an important regulator of local MCP-1 expre...
The possible beneficial effect of regular aquatic exercise on cardiorespiratory, renal lipid parameters and oxidative stress status was studied in patients with mild to moderate renal failure. The exercise group did low-intensity aerobic exercise in the pool during a period of 12 weeks, twice a week, with sessions lasting for 30 min. Matched control participants remained sedentary. The results showed that in the exercise group all cardiorespiratory functional parameters improved and resting blood pressure lowered significantly. Proteinuria and cystatin-C were diminished significantly and glomerular filtration rate was enhanced. To evaluate the changes in oxidative stress status in the serum, products of lipid peroxidation (LPO) and serum glutathione values were measured. LPO was reduced significantly and reduced glutathione levels showed significant improvement after the exercise-conditioning programme. In the control group the data either remained the same or worsened in the same period of time. In conclusion, regular water-based exercise has beneficial effects on the cardiorespiratory, renal functional parameters and oxidative stress status in patients with moderate renal failure, and can be used in the complex rehabilitation of chronic renal failure patients, together with blood pressure control, dietary consultation, encouragement and education to prevent physical worsening and to postpone cardiovascular and renal atherosclerotic complications.
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