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U Helmchen

Publications and source records attributed to U Helmchen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effect of renovascular hypertension on experimental glomerulonephritis in rats.

Systemic hypertension is a major risk factor that determines the rate of progression of kidney disease. The underlying mechanisms, however, are incompletely understood. To gain insight into these mechanisms, the present study was undertaken to characterize the effects of renovascular hypertension on the course of anti-thymocyte antibody-induced glomerulonephritis. Glomerulonephritis was induced in rats 6 weeks after the initiation of two-kidney, one-clip hypertension, when blood pressure was already increased. Structure and function of the clipped and the nonclipped kidney were examined 5 days later. Glomerular filtration rate (GFR) was measured by inulin clearance. The induction of nephritis did not alter the blood pressure in either hypertensive rats or normotensive controls. Albuminuria increased slightly in normotensive rats after the induction of nephritis, whereas no significant differences were found between hypertensive rats with or without nephritis. No significant differences were found for the GFR values of normotensive controls and nephritic animals or for values in the clipped kidney with or without nephritis. However, the GFR of the nonclipped kidney was significantly reduced in nephritic animals as compared with all other groups. Morphologic evaluation revealed that hypertensive rats with nephritis exhibited a combination of characteristics of nephritis and hypertensive glomerular injury. Histologic findings of nephritis, such as glomerular binding of rabbit IgG and glomerular proliferation and mesangial matrix expansion, were similar after the induction of nephritis in controls and in the clipped and nonclipped kidneys of hypertensive animals. However, intraglomerular microaneurysms were significantly more often found in the non-clipped kidneys after the induction of nephritis. Hypertension-induced deterioration of glomerular function was not associated with marked morphologic deterioration but rather with a combination of the characteristics of nephritis and hypertensive glomerular injury.

Albuminuria↗
PubMed1999

Cyclooxygenase metabolites mediate glomerular monocyte chemoattractant protein-1 formation and monocyte recruitment in experimental glomerulonephritis.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) has been shown to play a significant role in the recruitment of monocytes/macrophages in experimental glomerulonephritis. Whereas a number of inflammatory mediators have been characterized that are involved in the expression of MCP-1 in renal disease, little is known about repressors of chemokine formation in vivo. We hypothesized that cyclooxygenase (COX) products influence the formation of MCP-1 and affect inflammatory cell recruitment in glomerulonephritis. METHODS: The effect of COX inhibitors was evaluated in the antithymocyte antibody model and an anti-glomerular basement membrane model of glomerulonephritis. Rats were treated with the COX-1/COX-2 inhibitor indomethacin and the selective COX-2 inhibitors meloxicam and SC 58125. Animals were studied at 1 hour, 24 hours, and 5 days after induction of the disease. RESULTS: Indomethacin, to a lesser degree the selective COX-2 inhibitors, enhanced glomerular MCP-1 and RANTES mRNA levels. Indomethacin enhanced glomerular monocyte chemoattractant activity an the infiltration of monocytes/macrophages at 24 hours and 5 days. CONCLUSIONS: Our studies demonstrate that COX products may serve as endogenous repressors of MCP-1 formation in experimental glomerulonephritis. The data suggest that COX-1 and COX-2 products mediate these effects differently because the selective COX-2 inhibitors had less influence on chemokine expression.

Animals↗
PubMed1999

Monocyte chemoattractant protein-1 mediates collagen deposition in experimental glomerulonephritis by transforming growth factor-beta.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) plays a significant role in the recruitment of monocytes/macrophages in experimental glomerulonephritis (GN). Because recent evidence points to possible profibrogenic effects of leukocyte-derived factors in GN, this study was designed to evaluate the role of the chemokine MCP-1 in the fibrogenesis of experimental GN. METHODS: Rats with an anti-thy-1-induced GN were treated with a neutralizing antiserum against MCP-1. Glomerular collagen type IV, as a marker of glomerular matrix deposition, was assessed by Northern and Western blotting and immunohistology. Transforming growth factor-beta (TGF-beta), an important mediator of this matrix expansion, was studied by Northern and Western blotting. RESULTS: The induction of GN resulted in a significant increase of glomerular collagen type IV deposition and TGF-beta synthesis. The neutralization of MCP-1 significantly reduced the enhanced collagen type IV protein synthesis and deposition without affecting collagen mRNA expression. However, both the enhanced transcription and protein synthesis of TGF-beta were inhibited by anti-MCP-1 antiserum in nephritic animals. CONCLUSIONS: In this model of GN, MCP-1 has a fibrogenic effect through the stimulation of TGF-beta. MCP-1 is thus not only important for the recruitment of inflammatory cells, but also mediates glomerular matrix accumulation.

Animals↗
PubMed1999

Leptin stimulates proliferation and TGF-beta expression in renal glomerular endothelial cells: potential role in glomerulosclerosis [seecomments].

BACKGROUND: Leptin inhibits food intake and increases energy expenditure. Although the kidney expresses abundant transcripts of the short form of the leptin receptor (Ob-Ra), a role for this hormone in renal function remains unclear. Because individuals with massive obesity who may exhibit increased leptin serum concentrations develop renal glomerulosclerosis, we studied whether leptin can influence renal growth and profibrogenic processes. METHODS: The effects of recombinant leptin on proliferation and synthesis of transforming growth factor-beta1 (TGF-beta1) was investigated in cultured glomerular endothelial cells of the rat (GERs) and syngeneic mesangial cells. Furthermore, leptin receptor expression and potential signal transduction pathways were evaluated in GERs. In addition, leptin was also infused for different time periods (72 hr and 3 weeks) into naive rats. RESULTS: Recombinant mouse leptin induced proliferation of GERs, but not of syngeneic mesangial cells. Coincubation with angiotensin II and leptin exerts additive proliferative effects in GERs. An antileptin-receptor antibody totally abolished this proliferation but did not influence serum-induced proliferation. GER expressed high affinity receptors of the Ob-Ra type (Kd, 4 nM; Bmax, 9700 receptors/cell). Leptin also stimulated phosphorylation of STAT1alpha, and kinase inhibitors attenuated proliferation, suggesting a pivotal role of phosphorylation in this process. Incubation of GERs with leptin also induced mRNA expression of TGF-beta1 and enhanced secretion of this profibrogenic cytokine. Short-term leptin infusion (72 hr) into naive rats induced a significant proliferation, mainly restricted to glomerular endothelial cells, and enhanced glomerular TGF-beta1 mRNA levels. In rats continuously infused for three weeks with leptin, glomerular TGF-beta1 expression was still enhanced, and an additional increase in glomerular collagen type IV mRNA and protein expression was detected. These animals revealed an increase in proteinuria compared with control-infused rats. CONCLUSION: Our findings are the first in vitro and in vivo demonstration that leptin is a renal growth and profibrogenic factor. These results may be an important contribution to our understanding of how leptin can contribute to renal damage, characterized by endocapillary proliferation and subsequent development of glomerulosclerosis, in pathophysiological situations with high circulating levels such as in diabetics or obese individuals. Although the effects of leptin itself are moderate, growth-promoting and profibrogenic effects may be enhanced in concert with other factors such as angiotensin II.

Animals↗
PubMed1999

Extracellular matrix deposition and cell proliferation in a model of chronic glomerulonephritis in the rat.

BACKGROUND: Resident glomerular cell proliferation, matrix deposition and secretion of matrix metalloproteinases play a major role in the progression of chronic glomerular disease. These features were studied in a novel approach in a rat model of chronic glomerulonephritis induced by four injections of an anti-Thy 1.1 antiserum at weekly intervals. METHODS: Chronic immune mediated mesangial injury was induced in male Sprague-Dawley rats by repeated intravenous injection of an anti-Thy 1.1 antiserum. One week after the first and fourth injection of the antiserum proteinuria was evaluated and the kidneys were removed. Immunohistology was performed for proliferating cells, monocytes and collagen type IV. Furthermore, mRNA expression of collagen type IV, TGF-beta and the matrix degrading enzyme MMP-2 as well as MMP-2 protein expression were studied. RESULTS: Urinary protein excretion was dramatically increased after one antiserum injection and stayed elevated at a lower level after the fourth antiserum injection. After the initial induction of nephritis, 7 days following antiserum, resident glomerular cell proliferation was increased whereas with repeated injections of the antiserum cell numbers were not different from controls, as measured 1 week after the fourth injection. In contrast, extracellular matrix accumulation (collagen type IV) increased after the first antiserum injection and further increased after the fourth antiserum injection. The mRNA expression for collagen type IV increased after the first antiserum injection and showed further increase after the fourth antiserum injection. Induction of nephritis also stimulated glomerular mRNA expression of MMP-2 and TGF-beta, both of which remained at a high level after the fourth antiserum injection. Glomerular protein levels of MMP-2 also increased after the first antiserum injection and showed a further slight increase after the fourth injection. CONCLUSION: Increased cellular proliferation is involved in an early stage of this disease, while enhanced expression of glomerular matrix and augmented mRNA and protein expression of the matrix degrading enzyme MMP-2 continue into the chronic phase, and contribute to the extensive structural remodeling process that accompanies this form of glomerular injury.

Animals↗
PubMed1999

Histology and ultrastructure of liver and kidney following blood exchange with ultrapurified, polymerised bovine hemoglobin in comparison with hydroxyethyl starch.

Because of their oxygen binding capacity, cell-free hemoglobin solutions are promising blood substitutes. However, their clinical use has so far been limited by toxic side effects on liver and kidney until ultrapurification and chemical modifications have been established in the production process of hemoglobin-based oxygen carriers. The present study has been designed to examine structural changes of liver and kidney by light and electron microscopy after complete isovolemic blood exchange with a new ultrapurified bovine hemoglobin solution (UPBH-2) in eight beagle dogs. The results have been compared with a sham-operated control and eight animals having undergone blood exchange with hydroxyethyl starch (HES), a clinically used colloidal volume substitute. In the kidney, no changes were observed after blood exchange with UPBH-2 as compared with the sham control. These findings indicate sufficient tissue oxygenation and lack of renal toxicity. In contrast, histological signs of severe proximal tubular damage, eg, wide lumina, cytoplasmic protrusions, brush-border defects, and tubular necroses, were seen after blood exchange with HES. These changes are consistent with hypoxic tissue damage. In the liver, a slight increase in the number of single cell necroses was observed after UPBH-2 treatment as well as after blood exchange with HES. At the ultrastructural level, partial loss of microvilli and cytoplasmic protrusions of hepatocytes as well as swelling of endothelial cells were present in both groups, but slightly more pronounced in the UPBH-2 group. In all UPBH-2-treated animals, a marked diminution of glycogen-granula in hepatocytes was observed indicating an influence of UPBH-2 upon glycogen metabolism. Whereas the alterations of hepatocytes after nearly complete blood exchange with HES can be interpreted as a consequence of tissue hypoxia, the ultrastructural changes after UPBH-2 treatment cannot be attributed to hypoxic conditions, because improved tissue oxygenation has been demonstrated during treatment with UPBH-2. Hepatocyte damage was very discrete and comparable with the alterations observed after HES treatment. Hence, major hepatotoxicity can be excluded. The absence of significant adverse effects on the ultrastructural integrity of the kidney indicates that UPBH-2, owing to ultrapurification and polymerization, is an oxygen-carrying hemoglobin without acute renal toxicity.

Animals↗
PubMed1999

Kidney involvement in a 17-year-old boy with eosinophilic fasciitis.

Eosinophilic fasciitis (EF) is characterized by symmetrical scleroderma-like induration of skin over one or more distal extremities, peripheral eosinophilia, absence of Raynaud phenomenon and visceral involvement and a favourable response to systemically administered corticosteroids. Like other scleroderma-like disorders EF is rarely described in children. We report renal involvement in a 17-year-old boy with EF. Urinalysis disclosed proteinuria. Prior to corticosteroid therapy renal biopsy was performed which revealed ischemic collapse of glomerular capillaries and atrophy of tubules of the cortex. Electron-microscopic studies showed hyperplasia of the renin-producing epitheloid cells in the juxtaglomerular apparatus. Few other publications have depicted renal involvement in EF of quite different character. In these cases renal biopsy and histological classification is warranted because of prognostic and therapeutic implications.

Adolescent↗
PubMed1998

[Primary Sjögren's syndrome and glomerulonephritis].

HISTORY AND CLINICAL FINDINGS: An 82-year-old woman with hypertension for 20 years developed a nephrotic syndrome with severe oedema followed by acute oliguric renal failure after a bout of bronchitis and a gastrointestinal infection. She also complained of xerostomia and dry eyes of recent onset. INVESTIGATIONS: Biochemical tests showed a serum creatinine level of 6.1 mg/dl, a 1:5120 antinuclear antibody (ANA) titre, and positive values for Ro(SS-A) and La(SS-B) antibodies. HLA-DR typing demonstrated HLA-DR3 (HLA-DRB1*0301) and DR13 (HLA-DRB1*13) antigens. Renal biopsy revealed minimal glomerular lesions with focal and segmental glomerulo-sclerosis as well as (hypertension-induced) benign nephrosclerosis and focal tubular atrophy with interstitial fibrosis. TREATMENT AND COURSE: After two hemofiltrations and concomitant administration of 100 mg prednisone renal function quickly improved and the proteinuria fell to 1 g/dl. At the same time the xerostomia improved. The nephrotic syndrome recurred 7 months later after the prednisone dose had been reduced to 10 mg/d, but after the dose had been raised to 50 mg/d and cyclosporin A (150 mg/d) had been added a lasting remission occurred and renal function became stable though impaired. CONCLUSION: The relatively rare association of glomerular disease (here focal segmental glomerulosclerosis) with Sjögren's syndrome can, as in this case, be triggered by a viral infection. A genetic predisposition for Sjögren's syndrome is suggested by the demonstration of HLA-DR3 alleles. Administration of steroids is indicated for the treatment of the nephrotic syndrome and, in case of recurrence, can be combined with cyclosporin A. Both drugs also influence the symptoms of Sjögren's syndrome.

Aged↗
PubMed1998

[Spectrum of hypereosinophilia syndrome based on 2 clinical case reports].

BACKGROUND: Two severe cases of hypereosinophilic syndrome with cardiopulmonary symptoms, erythema nodosum, eosinophilic ileocolitis and paresthesia are reported. Definition, etiology, pathophysiological mechanisms, types, complications and therapeutic approaches of this relatively rare clinical disorder are discussed on the basis of these two cases. The distinction between eosinophilia and hypereosinophilic syndrome is clearly defined. DIFFERENTIAL DIAGNOSIS: The 2 cases of hypereosinophilic syndrome demonstrate the difficulty to decide whether they represent the idiopathic or the reactive type of hypereosinophilic syndrome. If the assumption is made in favor of the reactive type of hypereosinophilic syndrome the assumed prognosis could eventually be too promising. In case of an assumed idiopathic type of hypereosinophilic syndrome the search for causing factors like allergens could be left out. The decision concerning the type of hypereosinophilic syndrome of the 2 cases reported was made with high probability. In the case of idiopathic hypereosinophilic syndrome, eosinophilic leukemia was excluded by bone marrow biopsy. CONCLUSION: In order to be able to make a diagnosis it is necessary to search carefully for causing and influencing factors of the hypereosinophilic syndrome such as allergens or medicaments and to eliminate them. The hypereosinophilic syndrome must be put under frequent control in order to avoid complications or to start with therapeutic approaches in time.

Adult↗
PubMed1998

Spectrum of early onset nephrotic syndrome associated with WT1 missense mutations.

We investigated 17 children with nephrotic syndrome (NS) of early onset (14 aged < 1 year) and rapid progression to end-stage renal disease for the presence of mutations in the Wilms' tumor suppressor gene WT1 on chromosome 11. In eight children (7 genotypic males) an association with Wilms' tumor and/or ambiguous genitalia (Denys-Drash syndrome) was observed. In these eight and two additional female patients with NS only constitutional missense mutations in the WT1 gene were detected; four children presented the so-called hot spot mutation in exon 9 (R394N) and six had different mutations in exons 8 and 9 (4 not previously described). Renal biopsy showed diffuse mesangial sclerosis in eight and focal segmental sclerosis in two cases. End-stage renal disease was reached either concomitantly or within four months after onset of NS in seven of ten patients. A unilateral Wilms' tumor was found before or concomitant with NS in four children (3 males, 1 female). From the seven genotypic males with WT1 mutations, five presented ambiguous genitalia and two a female phenotype. No mutation of the WT1 gene was found in seven other children with isolated congenital or infantile NS with or without DMS who appeared to have a slower progression than the first group. It is proposed that patients with early onset, rapidly progressive NS and diffuse mesangial or focal segmental sclerosis should be tested for WT1 mutations to identify those at risk for developing Wilms' tumor.

Base Sequence↗
PubMed1998

Glomerular expression of p27Kip1 in diabetic db/db mouse: role of hyperglycemia.

Early diabetic nephropathy is characterized by glomerular hypertrophy. Previous studies in vitro have demonstrated that mesangial cells exposed to high glucose are arrested in the G1-phase of the cell cycle and express increased levels of the cyclin-dependent kinase inhibitor p27Kip1. The present study was performed to investigate the renal expression of p27Kip1 in db/db mice, a model of diabetes mellitus type II. Glomerular p27Kip1 protein, but not mRNA expression, was strongly enhanced in diabetic db/db mice compared with non-diabetic db/+ littermates. Immunohistochemical studies revealed that this stimulated expression was mainly restricted to the nuclei of mesangial cells and podocytes, but glomerular endothelial cells occasionally also stained positively. Quantification of p27Kip1 positive glomerular cells showed a significant increase of these cells in db/db mice compared with non-diabetic db/+ animals. Although tubular cells revealed a positive staining for p27Kip1 protein, there was no difference between db/+ and db/db mice. Immunoprecipitation experiments revealed that p27Kip1 protein associates with Cdk2 and Cdk4, but not with Cdk6. To test for the influence of hyperglycemia on cell cycle arrest and p27Kip1 expression, mesangial cells were isolated from db/+ and db/db mice. There was a similar basal proliferation when these cells were grown in normal glucose-containing medium (100 mg/dl). However, raising the glucose concentration to 275 to 450 mg/dl induced cell cycle arrest in db/+ as well as db/db mesangial cells. Increasing the medium osmolarity with D-mannitol failed to induce p27Kip1 expression in mesangial cells. Transfection of cells with p27Kip1 antisense, but not missense, phosphorothioate oligonucleotides facilitated cell cycle progression equally well in db/+ and db/db mesangial cells. Furthermore, p27Kip1 expression was comparable in both cell lines in normal glucose, but increased in high glucose medium. Our studies demonstrate that p27Kip1 expression is enhanced in diabetic db/db animals. This induction appears to be due to hyperglycemia. Expression of p27Kip1 may be important in cell cycle arrest and hypertrophy of mesangial cells during early diabetic nephropathy.

Animals↗
PubMed1998

L-arginine suppresses lipopolysaccharide-induced expression of RANTES in glomeruli.

Endotoxemia leads to the infiltration of inflammatory cells in glomeruli and the tubulointerstitium of the kidney. The ultimate mechanisms for this infiltration, however, are not entirely clear. In this study, the glomerular formation of the chemokine RANTES (regulated upon activation normal T cell expressed and secreted) was examined in an in vivo model of endotoxemia to evaluate the role the local release of chemokines might play in the regulation of this inflammatory cell infiltrate. Since the beneficial effects of nitric oxide (NO) on immune-mediated tissue injury have been reported, we also examined possible interactions between the chemokine RANTES and the L-arginine/NO pathway. To induce endotoxemia, rats were injected intraperitoneally with lipopolysaccharide (LPS). Glomeruli were isolated over a 24-h time period, and RANTES was assessed by Northern blotting, a chemotactic assay, and a specific enzyme-linked immunosorbent assay. The chemokine release was associated with increased glomerular infiltration of monocytes/macrophages. LPS also stimulated the mRNA expression of inducible NO synthase and increased the release of nitrite into the supernatants of isolated glomeruli. Supplementation of L-arginine intake increased the release of glomerular nitrite and reduced glomerular RANTES expression after the injection of LPS. Inhibition of the L-arginine/NO pathway by the unspecific NO synthase inhibitor N(G)-nitro-L-arginine methylester significantly increased glomerular RANTES mRNA expression and the number of infiltrating glomerular macrophages. These data demonstrate that L-arginine suppresses glomerular RANTES formation and suggest that the chemokine-mediated recruitment of glomerular macrophages in LPS-induced endotoxemia can be modulated by the L-arginine/NO pathway.

Animals↗
PubMed1998

Regulation of glomerular TGF-beta expression in the contralateral kidney of two-kidney, one-clip hypertensive rats.

Previous studies have demonstrated that angiotensin II stimulates expression of transforming growth factor-beta (TGF-beta) in cultured renal cells. To investigate whether similar mechanisms are operative in vivo, glomerular TGF-beta mRNA expression was investigated in two-kidney, one-clip (2-K 1-C) hypertensive rats. Glomerular TGF-beta1 transcripts were elevated in the clipped kidney 6 d, but not 3 d, after surgery. Later, during the course of the disease (21 to 35 d), TGF-beta1 mRNA was upregulated in contralateral kidneys compared with sham-operated control kidneys. There was no difference in plasma TGF-beta1 levels between 2-K 1-C rats and controls. Treatment with the AT1 receptor antagonist losartan, as well as with triple therapy (hydralazine, reserpine, and hydrochlorothiazide), started 1 d after clipping, significantly reduced systolic BP in hypertensive rats at day 21 after clipping. Both treatments were equally effective in preventing the increase in glomerular TGF-beta1 mRNA and protein expression in the contralateral kidney at day 21. In a second set of experiments, interventional treatment with losartan or triple therapy, starting 14 d after surgery, was investigated. This treatment for 3 wk significantly reduced the increase in TGF-beta1 expression in the contralateral kidney. At day 35 after clipping, considerable glomerular damage and sclerosis were present, mainly in contralateral kidneys. Interventional treatment with losartan or triple therapy partly prevented this glomerular damage of the contralateral kidney. The data demonstrate that TGF-beta1 expression in the contralateral kidney in 2-K 1-C rats is regulated by the increase in systemic BP rather than by direct effects of angiotensin II.

Animals↗
PubMed1998

Remission of IgA nephropathy following treatment of cytomegalovirus infection with ganciclovir.

Following the detection of cytomegalovirus antigen in mesangial cells of some patients with IgA nephropathy, an important role of human cytomegalovirus in the pathogenesis of IgA nephropathy has been discussed. We studied a case of IgA nephropathy with rapid deterioration of renal function associated with cytomegalovirus infection. Following an infection of the upper respiratory tract, a 57-year-old woman developed with hematuria and acute renal failure. The histological diagnosis of IgA nephropathy was established and renal function transiently improved during immunosuppressive therapy. However, the ensuing clinical course was complicated by severe bleeding from intestinal ulcera, thrombocytopenia, pneumonia and relapse of renal failure. The histological investigation of colonic mucosa showed characteristic "owl's eye" cells leading to the diagnosis of cytomegalovirus disease as the cause of intestinal bleeding. Immunosuppression was stopped and treatment with ganciclovir started. Pneumonia as well as intestinal bleeding disappeared and, of particular note, renal function improved considerably. Following discontinuation of antiviral therapy CMV-disease reoccurred and renal function deteriorated again. The patient was restarted on ganciclovir therapy and, again, serum creatinine fell quickly. This impressive and reproducible clinical improvement of renal insufficiency under antiviral therapy with ganciclovir provides some evidence for an important role of cytomegalovirus in the pathogenesis of this case of IgA nephropathy.

Antiviral Agents↗
PubMed1997

Angiotensin II stimulates expression of the chemokine RANTES in rat glomerular endothelial cells. Role of the angiotensin type 2 receptor.

Glomerular influx of monocytes/macrophages (M/M) occurs in many immune- and non-immune-mediated renal diseases. The mechanisms targeting M/M into the glomerulus are incompletely understood, but may involve stimulated expression of chemokines. We investigated whether angiotensin II (ANG II) induces the chemokine RANTES in cultured glomerular endothelial cells of the rat and in vivo. ANG II stimulated mRNA and protein expression of RANTES in cultured glomerular endothelial cells. The ANG II-induced RANTES protein was chemotactic for human monocytes. Surprisingly, the ANG II-stimulated RANTES expression was transduced by AT2 receptors because the AT2 receptor antagonists PD 123177 and CGP-42112A, but not an AT1 receptor blocker, abolished the induced RANTES synthesis. Intraperitoneal infusion of ANG II (500 ng/h) into naive rats for 4 d significantly stimulated glomerular RANTES mRNA and protein expression compared with solvent-infused controls. Immunohistochemistry revealed induction of RANTES protein mainly in glomerular endothelial cells and small capillaries. Moreover, ANG II- infused animals exhibited an increase in glomerular ED-1- positive cells compared with controls. Oral treatment with PD 123177 (50 mg/liter drinking water) attenuated the glomerular M/M influx without normalizing the slightly elevated systolic blood pressure caused by ANG II infusion, suggesting that the effects on blood pressure and RANTES induction can be separated. We conclude that the vasoactive peptide ANG II may play an important role in glomerular chemotaxis of M/M through local induction of the chemokine RANTES. The observation that the ANG II- mediated induction of RANTES is transduced by AT2 receptors may influence the decision as to which substances might be used for the therapeutic interference with the activity of the renin-angiotensin system.

Angiotensin II↗