Biomedical subjects

Kerstin Amann

Publications and source records attributed to Kerstin Amann.

95 records · Page 6Linked to original sources

PubMed2000

Effects of low dose sympathetic inhibition on glomerulosclerosis and albuminuria in subtotally nephrectomized rats.

ABSTRACT.: A potential role of the sympathetic nervous system in progression of renal failure has received little attention. This study examined whether nonhypotensive doses of moxonidine, an agent that reduces sympathetic activity, affects glomerulosclerosis, urine albumin excretion, and indices of renal handling of norepinephrine (NE) in subtotally nephrectomized (SNX) rats. Sprague Dawley rats were SNX or sham-operated (control). SNX rats were either left untreated or treated with moxonidine in a dose (1.5 mg/kg body wt per d) that did not modify telemetrically monitored 24-h BP. Glomerular and renal morphology were evaluated by quantitative histology, immunohistochemistry, and in situ hybridization. Urine albumin excretion rate was analyzed by enzyme-linked immunosorbent assay, and kidney angiotensin II and NE content were measured using HPLC, (3)H-NE uptake, and release. Body and kidney weight and BP were not significantly different between SNX with or without moxonidine. The glomerulosclerosis index was significantly lower in moxonidine-treated (0.88 +/- 0.09) compared with untreated (1.55 +/- 0.28) SNX rats, as was the index of vascular damage (0.32 +/- 0.14 versus 0.67 +/- 0.16). The number of proliferating cell nuclear antigen-positive glomerular and tubular cells per area was significantly higher in untreated SNX rats than in controls and moxonidine-treated SNX rats. The same was true for urine albumin excretion rate. Renal angiotensin II tissue concentration was not affected by moxonidine. In untreated SNX rats, renal nerve stimulation and exogenous NE induced an increase in isolated kidney perfusion pressure (102 +/- 21 versus 63 +/- 8 mmHg). Renal endogenous NE content was significantly lower in SNX rats than in controls (86 +/- 14 versus 140 +/- 17 pg/mg wet weight). Cortical uptake of [(3)H]-NE was not different, but cortical NE release was significantly higher in SNX rats than in controls. Reduced function of presynaptic inhibitory alpha-adreno-receptors is unlikely because an alpha(2)-adrenoceptor antagonist increased NE release. At subantihypertensive doses, moxonidine ameliorates renal structural and functional damage in SNX animals, possibly through central inhibition of efferent sympathetic nerve traffic. In kidneys of SNX rats, indirect evidence was found for increased activity of a reduced number of nerve fibers.

Albuminuria↗

PubMed2000

Retinoic acid reduces glomerular injury in a rat model of glomerular damage.

ABSTRACT.: In the reaction of kidneys to injury, cytokine-driven proliferation plays an important role and precedes the development of glomerulosclerosis. There is great interest in agents that may interfere with such proliferation. Therefore, a rat model of mesangioproliferative glomerulonephritis (induced by anti-Thy1.1) was studied, and the effects of all-trans-retinoic acid (all-trans-RA) and isotretinoin, powerful antiproliferative and anti-inflammatory substances, on glomerular damage and cell proliferation were examined. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all-trans-RA or 40 mg/kg body wt isotretinoin (n = 9 to 11 per group), using either a pretreatment (days -2 through 8) or posttreatment (days +3 through +8) protocol, i.e., starting before or after the induction of anti-Thy1.1 nephritis, respectively. All-trans-RA prevented the BP increase evoked by anti-Thy1.1 (anti-Thy1.1/vehicle, 112.2 +/- 4.8 mmHg; anti-Thy1.1/RA, 87.5 +/- 2. 5 mmHg; P < 0.001). Treatment with all-trans-RA or isotretinoin produced a 70% decrease in the urinary albumin excretion rate (P < 0. 02). Periodic acid-Schiff staining of saline-perfused kidneys (day 8) revealed significantly fewer glomerular cells in RA-treated nephritic rats (anti-Thy1.1/vehicle, 97 +/- 3.1 cells/glomerulus; anti-Thy1.1/RA, 80 +/- 4.4; P < 0.02; control/vehicle, 69 +/- 1.2). No difference was observed between all-trans-RA and isotretinoin treatment. The capillary occlusion scores were significantly lower for the anti-Thy1.1/RA-treated group (1.9 +/- 0.1) than for the anti-Thy1.1/vehicle-treated group (2.9 +/- 0.5, P < 0.001). In the anti-Thy1.1/vehicle-treated group, 11.9 +/- 1.1 glomerular cells were proliferating cell nuclear antigen-positive; however, in the anti-Thy1.1/RA-treated group, only 5.3 +/- 0.8 cells were proliferating cell nuclear antigen-positive (P < 0.002; control, 2.2 +/- 0.2). Glomerular mitoses were reduced by 67% in the anti-Thy1. 1/RA-treated group, compared with the anti-Thy1.1/control group (P < 0.002). Glomerular staining for platelet-derived growth factor B-chain was significantly reduced in anti-Thy1.1-treated nephritic rats in the presence of isotretinoin or all-trans-RA, compared with the vehicle-treated group (P < 0.001). It is concluded that all-trans-RA limits glomerular proliferation, glomerular lesions, and albuminuria in an established model of renal damage. The findings point to retinoids as potential novel modulators of glomerular injury.

Albuminuria↗

PubMed2000

Endothelin A receptor blockade prevents capillary/myocyte mismatch in the heart of uremic animals.

In the heart of uremic animals and patients, the number of capillaries per volume of myocardium is reduced. Immunohistochemical studies demonstrated increased cardiac endothelin-1 (ET-1) expression in the left ventricle of uremic animals. Therefore, whether treatment with a selective ET(A)-receptor antagonist prevented such capillary-myocyte mismatch was investigated. Twenty-four h after subtotal nephrectomy, rats were left untreated or started on treatment with the ET(A)-receptor antagonist LU 135252 (20 mg/kg per d) and with the angiotensin-converting enzyme (ACE) inhibitor trandolapril (0.3 mg/kg per d), respectively. BP was monitored by telemetry. Myocardial capillary length density was analyzed by stereologic techniques that avoid anisotropy artifacts. In addition, cardiac ET-1 protein and mRNA were measured using immunohistochemistry, in situ hybridization, and quantitative reverse transcription-PCR. Changes in cardiac ET(A)-and ET(B)-PCR. receptor mRNA were measured using reverse transcription-PCR. Fifteen wk after subtotal nephrectomy, significantly reduced left ventricular capillary length density (3307 +/- 535 mm/mm(3)) was found compared with sham-operated controls (3995 +/- 471 mm/mm(3)); this was also seen in animals that were treated with trandolapril (3503 +/- 533 mm/mm(3)) but not in animals that were treated with LU 135252 (3800 +/- 303 mm/mm(3)). The results support a role of ET-1 in the genesis of left ventricular capillary/myocyte mismatch in uremia.

Angiotensin-Converting Enzyme Inhibitors↗

PubMedDate not supplied

Transforming growth factor-beta receptor-II up-regulation during wound healing in previously irradiated graft beds in vivo.

Wound healing disorders may often present in patients with head and neck cancer after surgical interventions, particularly in preirradiated tissue. Inflammatory changes and the expression of cytokines can lead to induction of fibrosis. The isoforms of the transforming growth factor beta (TGFbeta1-3) play a key role for this process. It has been shown that radiation treatment associated fibrosis is induced by TGFbeta1 and TGFbeta2, although the influence of radiation on the expression of the TGFbeta receptor-II (TGFbetaR-II) involved in the signal transduction of TGFbeta remains elusive. The objective of this in vivo study was to analyze the expression profile of TGFbetaR-II in the graft bed and in the transition area between graft and graft bed after surgery with and without prior radiation treatment to compare with the expression profiles of activated TGFbeta1 and latency-associated peptide. A total of 48 Wistar rats (male, weight 300-500 g) were used in the study. Eighteen rats were irradiated in the neck region (3 x 10 Gy) without transplantation. A free myocutaneous gracilis flap was transplanted in 30 rats, of which 16 animals were preirradiated in the neck region (3 x 10 Gy) and 14 animals were not irradiated at all. Tissue samples were taken postoperatively from the transition area between the graft and the graft bed and from the graft bed itself after 3, 7, 14, and 28 days. Tissue samples were taken from the irradiated neck region and the non-irradiated groin region 0, 4, 7, 11, 14, and 28 days after the end of the exposure. The expression of TGFbetaR-II, activated TGFbeta1 and latency-associated peptide was analyzed immunohistochemically both qualitatively and quantitatively (labeling index). The success rate for graft healing was 75% in the previously irradiated group with 30 Gy, and 86% in the non-irradiated group. Following radiation alone a significantly (p = 0.04) increased TGFbetaR-II expression in the neck was revealed 2-4 weeks following irradiation compared to non-irradiated skin. Whereas only minor differences in TGFbetaR-II expression were observed following surgery between the groups with and without prior radiation in the transition area between the graft and the graft bed, the group undergoing prior radiation and subsequent grafting showed significantly increased expression in the bed compared to the non-preirradiated group with a maximum on postoperative day 7 (week 1, p = 0.003; week 2-4, p < 0.001). In irradiated tissues the up-regulation of TGFbetaR-II expression correlated with an increase of activated TGFbeta1 and latency-associated peptide expression compared to non-irradiated tissues. After irradiation, a significantly increased TGFbetaR-II expression was identified in the irradiated graft bed, which may be the reason for delayed reepithelialization and fibrosis. Exogenous blocking or TGFbetaR-II inhibitors could therefore represent a new therapeutic approach for improving wound healing after preoperative radiotherapy.

Animals↗

PubMedDate not supplied

Mediators of inflammatory and ischemic renal damage: the role of neoangiogenesis.

Neoangiogenesis is at the forefront of research in a number of fields that are of interest to the nephrologist, ranging from the development of the kidney and glomerulus to microvascular injury and its repair. The molecular mechanisms have recently been elucidated to a considerable extent. They are relevant for understanding the link between endothelial cells and podocytes, which underlie the glomerular barrier function. For reasons poorly understood capillarogenesis is defective in renal failure.

Animals↗