losartan-potassium and Hypertrophy

Erythropoietin (rhEPO) is increasingly being used in the treatment of anemia caused by miscellaneous reasons. The aim of our research is to investigate the effects of recombinant human erythropoietin (rhEPO) on cellular growth and fibronectin (FN) expression in glomerular mesangial cells.. Western blot was used to detect the expression of FN induced by rhEPO (1, 10, 100 and 1000U/mL). In vivo studies, male CD-1 mice were administered rhEPO subcutaneously at a single dose of 1000U/Kg. The cellular hypertrophy was quantified by counting cell number and calculating the ratio of cell protein to cell number.. 1) Compared with the control group, the results of mesangial cells' growth stimulated by rhEPO were not significantly different; 2) RhEPO lead to hypertrophy of mesangial cells; 3) rhEPO induced FN expression of mesangial cell in a dose-dependent way. Compared to control, 100U/mL rhEPO enhanced the expression of FN significantly; 4) indirect immunofluorescence showed that rhEPO induced large amount deposition of FN in the intercellular space of mesangial cells; 5) in vivo studies, there were markedly increase of FN expression in mice received the injection of rhEPO.. RhEPO could up-regulated the expression of FN and induced glomerular mesangial cells hypertrophy. These results suggested rhEPO could induce dysfunction of renal glomerulus through its influence on the function of mesangial cells.

Topics: Animals; Cell Proliferation; Dose-Response Relationship, Drug; Erythropoietin; Fibronectins; Gene Expression Regulation; Humans; Hypertrophy; Kidney Glomerulus; Male; Mesangial Cells; Mice; Recombinant Proteins; Up-Regulation

A Standardbred gelding and a colt were examined because of poor performance and anemia. Each horse had been given recombinant human erythropoietin (rhEPO; 4,000 IU) at least twice within the preceding 2 to 4 months. The horses had an Het of 16 and 24%, serum iron concentrations of 210 and 304 micrograms/dl (reference range, 73 to 140 micrograms/dl), total iron binding capacities of 239 and 321 micrograms/dl (reference range, 266 to 364 micrograms/dl), values for the percentage saturation of transferrin by iron of 87.9 and 94% (reference range, 20 to 52%), and serum ferritin concentrations of 255 and 355 ng/ml (reference range, 43 to 261 ng/ml), respectively. There was no clinical or laboratory evidence of immune-mediated hemolysis or an infectious or inflammatory cause of the anemia. Examination of sternebral marrow biopsy specimens revealed generalized bone marrow hypoplasia; myeloid-to-erythroid ratios were 6.7 and 3.2. Moderate-to-marked erythroid hypoplasia was diagnosed in both horses. Compared with serum from a healthy control horse, serum from the affected horses inhibited rhEPO-induced proliferation of erythroid progenitors in vitro. Results suggested that the horses had developed anti-rhEPO antibodies that cross-reacted with endogenous erythropoietin, thereby inhibiting erythropoiesis. Horses were discharged with instructions that rhEPO administration be discontinued and that dexamethasone be administered. Five months later, both horses were back in training. For 1 horse, Hct had increased to 35%, and the other horse was not available for examination.

Topics: Anemia; Animals; Biopsy, Needle; Bone Marrow; Cross Reactions; Erythroid Precursor Cells; Erythropoietin; Horse Diseases; Horses; Humans; Hypertrophy; Male; Recombinant Proteins

The Han:SPRD rat model for inherited polycystic kidney disease (PKD) was characterized (clinical parameters, morphology, immunohistochemistry and in situ hybridization). Homozygous animals died of uremia after three to four weeks with severe cystic transformation of virtually all nephrons and collecting ducts (serum urea: 616 +/- 195 mg/dl; kidney-to-body weight ratio: > 20%). In heterozygotes, slow progression of the disease led to death between the 12th and 21st month (median: 17 months; serum urea levels above 200 mg/dl). Kidney enlargement was moderate, and cysts were restricted to the cortex and outer medulla. Immunohistochemical markers showed that approximately 75% of the cysts were derived from the proximal tubule. Cystic transformation started in the proximal tubule with a sharp onset of basement membrane alteration and a loss of epithelial differentiation restricted to small focal areas. In these areas, alpha 1(IV) collagen and laminin B1 mRNA were enhanced as revealed by isotopic and non-isotopic in situ hybridization. Fibroblasts underlying the affected tubular portions were involved in matrix overexpression resulting in subepithelial accumulation of immunoreactive collagen IV and laminin. In later stages of cystic transformation distal nephron segments were affected as well. A reversal in epithelial polarity as judged from Na,K-ATPase-immunoreactivity was not observed. Renal immunoreactive renin-status was significantly decreased. Hematocrit was lowered in heterozygotes (40.4 +/- 5.8 vol% compared to 46.7 +/- 1.99 vol% in controls; P < 0.05) and total renal EPO mRNA was reduced to 36 +/- 14% of the mean value of control animals, whereas serum EPO levels were not significantly altered. We conclude that the Han:SPRD rat is a useful model for the study of human ADPKD since both diseases are similar in several aspects. The model is particularly suitable for the study of epithelial-mesenchymal interactions at the beginning of tubular cystic transformation.

Topics: Animals; Disease Models, Animal; Erythropoietin; Extracellular Matrix Proteins; Female; Hypertrophy; Kidney; Male; Mucoproteins; Polycystic Kidney, Autosomal Dominant; Rats; Rats, Mutant Strains; Rats, Sprague-Dawley; Renin; RNA, Messenger; Sodium-Potassium-Exchanging ATPase; Uromodulin

Topics: Androgens; Animals; Body Weight; Erythropoiesis; Erythropoietin; Female; Hypertrophy; Hypoxia; Iron Isotopes; Kidney; Organ Size; Rats; Testosterone

Topics: Animals; Erythropoietin; Hypertrophy; Kidney; Kidney Diseases; Nephrectomy; Postoperative Complications; Rats; Tissue Extracts