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Dive into the research topics where Andrea Hartner is active.

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Featured researches published by Andrea Hartner.


Hypertension | 1998

Coordinate Expression of Cyclooxygenase-2 and Renin in the Rat Kidney in Renovascular Hypertension

Andrea Hartner; Margarete Goppelt-Struebe; Karl F. Hilgers

Prostaglandins contribute to the regulation of renin synthesis and secretion. We tested the hypothesis that the inducible isoform of prostaglandin G/H synthase, cyclooxygenase-2, contributes to the stimulation of renin synthesis in renovascular hypertension. The expression of cyclooxygenase-2 and renin was investigated in the kidneys of rats with two-kidney, one-clip renovascular hypertension or sham operation. Systolic blood pressure was increased 2 weeks after clipping (153+/-7 versus 112+/-4 mmHg in controls, n=6 each, P<.05) and continued to rise until 4 weeks. Cyclooxygenase-2 mRNA levels were increased in clipped kidneys but remained unchanged or slightly decreased in nonclipped kidneys. Cyclooxygenase-2 protein was expressed mainly in the macula densa and occasionally in distal tubular cells not associated with the macula densa. Two weeks after clipping, the percentage of juxtaglomerular apparatus staining positive for cyclooxygenase-2 was 27.8+/-3.6 in clipped kidneys, 3.1+/-0.4 in contralateral kidneys, and 8.0+/-1.3 in controls; the percentages for immunoreactive renin staining in the afferent arteriole were 33.6+/-2 in clipped kidneys, 1.9+/-0.5 in contralateral kidneys, and 12.4+/-4.0 in controls, respectively. Similar parallel changes in renin and cyclooxygenase-2 staining were observed 4 weeks after clipping. The percentage of cyclooxygenase-2-positive juxtaglomerular apparatus correlated positively with the percentage that was renin positive (r=0.78, P<.05). Double immunostaining showed coexpression of cyclooxygenase-2 and renin protein in the same juxtaglomerular apparatus. Our data are consistent with a role for macula densa cyclooxygenase-2 in the regulation of renin in renovascular hypertension.


Hypertension | 2008

(Pro)renin receptor peptide inhibitor "handle-region" peptide does not affect hypertensive nephrosclerosis in Goldblatt rats.

Dominik Müller; Bernd Klanke; Sandra Feldt; Nada Cordasic; Andrea Hartner; Roland E. Schmieder; Friedrich C. Luft; Karl F. Hilgers

The (pro)renin receptor [(P)RR], a new component the renin-angiotensin system, was cloned recently. The (P)RR promotes direct mitogen-activated protein kinase signaling and nonproteolytic prorenin activation. We investigated the role of a (P)RR blocker, a peptide consisting of 10 amino acids from the prorenin prosegment called the “handle-region” peptide (HRP), on target organ damage in renovascular hypertensive 2-kidney, 1-clip (2K1C) rats. Vehicle-treated 2K1C rats were compared with HRP-treated 2K1C rats (3.5 &mgr;g/kg per day) and sham-operated controls. Vehicle-treated 2K1C rats developed hypertension (186±17 mm Hg), cardiac hypertrophy (3.16±0.16 mg/g), renal inflammation, fibrosis, vascular, and tubular damage. Chronic HRP treatment did not affect blood pressure (194±15 mm Hg), cardiac hypertrophy (2.97±0.11 mg/g), or renal damage. Furthermore, we investigated the renal renin and (P)RR expression. The clipped kidney of 2K1C and HRP-treated 2K1C rats showed a higher renin expression and juxtaglomerular index compared with sham-operated kidneys. The unclipped kidney showed suppressed renin expression. In contrast, (P)RR mRNA expression was not altered in any group. Plasma renin activity and aldosterone were increased in 2K1C rats compared with sham controls. HRP-treated 2K1C rats tended to lower plasma renin activity but showed similar aldosterone levels as vehicle-treated 2K1C rats. Our results indicate that blockade of the (P)RR with HRP does not improve target organ damage in renovascular hypertensive rats.


Hypertension | 1999

Inhibition of the Renin-Angiotensin System Upregulates Cyclooxygenase-2 Expression in the Macula Densa

Konrad Wolf; Hayo Castrop; Andrea Hartner; Margarete Goppelt-Strübe; Karl F. Hilgers; Armin Kurtz

The expression of cyclooxygenase 2 (COX-2) in the late thick ascending limb, including the macula densa, is found to be upregulated in an activated renin-angiotensin system. How this upregulation is managed is not yet known. We therefore considered the possibility that the stimulation of COX-2 expression is triggered by the activation of the renin-angiotensin system. For this purpose, we treated male Sprague-Dawley rats with the angiotensin I-converting enzyme inhibitor ramipril (10 mg/kg per day), the angiotensin II type 1 (AT(1)) receptor blocker losartan (30 mg/kg per day), and the angiotensin II type 2 (AT(2)) receptor blocker PD123319 (6 mg/kg per day) for 4 days. We determined the expression of COX-2 mRNA and protein in the renal cortex. We found that ramipril and the AT(1) receptor blocker losartan increased COX-2 mRNA and COX-2 immunoreactivity in the macula densa approximately 4-fold, whereas the AT(2) blocker PD123319 showed no effect. A low-salt diet (0.02% wt/wt) stimulated COX-2 expression in the kidney cortex <2-fold. The combination of a low-salt diet with ramipril led to a further increase of COX-2 mRNA and COX-2 immunoreactivity compared with low salt or ramipril alone. These data indicate that endogenous angiotensin II apparently inhibits COX-2 expression in the macula densa via AT(1) receptors and can therefore not account for the stimulation of COX-2 expression associated with an activated renin-angiotensin system. Because macula densa-derived prostaglandins are considered stimulators of renin secretion and renin synthesis, inhibition of macula densa COX-2 by angiotensin II could form a novel indirect negative feedback control of the renin system.


Journal of The American Society of Nephrology | 2010

Telomere Shortening Reduces Regenerative Capacity after Acute Kidney Injury

Jens H. Westhoff; Carolin Schildhorn; Christoph Jacobi; Meike Hömme; Andrea Hartner; Heidi Braun; Christine Kryzer; Chunfang Wang; Thomas von Zglinicki; Bettina Kränzlin; Norbert Gretz; Anette Melk

Telomeres of most somatic cells progressively shorten, compromising the regenerative capacity of human tissues during aging and chronic diseases and after acute injury. Whether telomere shortening reduces renal regeneration after acute injury is unknown. Here, renal ischemia-reperfusion injury led to greater impairment of renal function and increased acute and chronic histopathologic damage in fourth-generation telomerase-deficient mice compared with both wild-type and first-generation telomerase-deficient mice. Critically short telomeres, increased expression of the cell-cycle inhibitor p21, and more apoptotic renal cells accompanied the pronounced damage in fourth-generation telomerase-deficient mice. These mice also demonstrated significantly reduced proliferative capacity in tubular, glomerular, and interstitial cells. These data suggest that critical telomere shortening in the kidney leads to increased senescence and apoptosis, thereby limiting regenerative capacity in response to injury.


Journal of The American Society of Nephrology | 2008

Autonomic Renal Denervation Ameliorates Experimental Glomerulonephritis

Roland Veelken; Eva-Maria Vogel; Karl F. Hilgers; Kerstin Amann; Andrea Hartner; Gabriele Sass; Winfried Neuhuber; Gisa Tiegs

Increasing evidence indicates that inflammation of visceral organs is significantly affected by the autonomic nervous system. Such neuroimmune interactions have not been studied in the kidney. Here, we show that the rat kidney is innervated by both tyrosine hydroxylase-positive sympathetic efferent nerve fibers and calcitonin gene-related peptide-positive primary afferent nerve fibers, both of which are found in proximity to macrophages and dendritic cells. Complete surgical bilateral renal denervation was performed 2 d before glomerulonephritis was induced by injecting the monoclonal anti-Thy-1.1 antibody OX-7. Denervation significantly reduced albuminuria, mesangiolysis, formation of microaneurysms, deposition of glomerular collagen IV, and expression of TGF-beta compared with sham-operated controls. Accordingly, inflammation, identified by accumulation of interstitial macrophages and renal expression of TNF-alpha, and mesangial cell proliferation were significantly reduced. These findings indicate that autonomic renal denervation ameliorates and, by inference, innervation exacerbates acute inflammation in the kidney; therefore, neurotransmitters or neuropeptides and their receptors might represent novel targets for the treatment of acute glomerulonephritis.


Journal of The American Society of Nephrology | 2003

Glomerular and renal vascular structural changes in α8 integrin-deficient mice

Christian S. Haas; Kerstin Amann; Johannes C. Schittny; Barbara Blaser; Ulrich Müller; Andrea Hartner

Integrins are matrix receptors that regulate cell-matrix interactions during development and in adult tissue. In the adult kidney, the alpha8 chain is specifically expressed in glomerular mesangial cells and vascular smooth muscle cells. alpha8-deficient (alpha8-/-) mice demonstrate reductions in renal mass, which can range from complete renal agenesis to the development of kidneys that are only slightly smaller than wild-type kidneys. No histologic abnormalities of these kidneys have been described. However, considering the prominent expression of alpha8 in glomeruli and renal vessels, it seemed unlikely that the kidneys of alpha8-/- mice would be completely normal. Therefore, the renal phenotype of adult alpha8-/- mice was investigated, for assessment of more subtle morphologic alterations in kidney tissue. alpha8-/- mice displayed a significant reduction in nephron number and an increase in glomerular volume, compared with wild-type control animals. Albuminuria was not different in wild-type and alpha8-/- mice. Quantitative morphologic analyses revealed that the glomeruli of alpha8-/- mice were hypercellular, with an increased number of mesangial cells, compared with wild-type mice. Mesangial matrix deposition (as demonstrated for collagen IV and the alpha8 ligand fibronectin) was expanded in alpha8-/- mice, compared with wild-type mice. Collagens I and III, which are not normally present in glomeruli, were detected in the glomeruli of alpha8-/- mice. Staining for other glomerular integrins demonstrated an increased abundance of the collagen receptor alpha2 integrin in alpha8-/- mice. The glomerular capillary length density was significantly greater in alpha8-/- mice than in wild-type mice. Cortical arterial vessel walls were not altered in alpha8-/- mice, but the capillaries of the peritubular network were widened. Despite the strong mesangial and vascular expression of alpha8, glomerular and renal vascular alterations in alpha8-/- mice were relatively mild. Only aged alpha8-/- mice demonstrated increased glomerular capillary widening, compared with control animals. The results suggest that the lack of alpha8 can be largely compensated for, at least in younger alpha8-/- mice. It is not yet clear whether the occurrence of collagens that are not normally present in glomeruli and the increased abundance of the collagen receptor alpha2 contribute to maintaining the glomerular structure in alpha8-/- mice. The compensatory mechanisms involved will be the subject of future research.


American Journal of Pathology | 2002

The α8 Integrin Chain Affords Mechanical Stability to the Glomerular Capillary Tuft in Hypertensive Glomerular Disease

Andrea Hartner; Nada Cordasic; Bernd Klanke; Ulrich Müller; R. Bernd Sterzel; Karl F. Hilgers

In the kidney, the alpha8 integrin chain is expressed in glomerular mesangial cells. The alpha8 integrin plays a role in early nephrogenesis but its functional role in the adult kidney is unknown. We tested the hypothesis that alpha8 integrin-mediated cell-matrix interactions are important to maintain the integrity of the glomerulus in arterial hypertension. Desoxycorticosterone (DOCA)-salt hypertension was induced in mice homozygous for a deletion of the alpha8 integrin chain and wild-type mice. Blood pressure, albumin excretion, total renal mass, and glomerular filtration in DOCA-treated alpha8-deficient mice were comparable to DOCA-treated wild types. DOCA-treated wild types showed increased glomerular immunostaining for alpha8 integrin compared to salt-loaded and untreated controls, whereas the glomeruli of alpha8-deficient mice always stained negative. Morphometric studies revealed similar degrees of glomerulosclerosis in DOCA-treated alpha8-deficient and DOCA-treated wild-type mice. However, DOCA-treated alpha8-deficient mice had a higher score of capillary widening (mesangiolysis) than DOCA-treated wild-type mice, which was confirmed in two additional wild-type strains. Moreover, in DOCA-treated alpha8-deficient mice, glomerular fibrin deposits were more frequent than in DOCA-treated wild types. The results show that lack of alpha8 is associated with increased susceptibility to glomerular capillary destruction in DOCA salt hypertension, whereas it does not seem to play a major role in the development of fibrosis or glomerulosclerosis. Our findings indicate that mesangial alpha8 integrin contributes to maintain the integrity of the glomerular capillary tuft during mechanical stress, eg, in hypertension.


Hypertension | 2001

Renin Uptake by the Endothelium Mediates Vascular Angiotensin Formation

Karl F. Hilgers; Roland Veelken; Dominik Müller; Hans Kohler; Andrea Hartner; Suzanne R. Botkin; Christian Stumpf; Roland E. Schmieder; R. Ariel Gomez

Abstract—We investigated the role of the vascular endothelium in the local production of angiotensin. Angiotensin release from isolated rat hindquarters perfused with an artificial medium was measured by high-performance liquid chromatography and radioimmunoassay. Perfused hindquarters with endothelium released angiotensin I spontaneously, indicating ongoing renin-angiotensinogen reaction. Endothelium denudation (by a detergent, validated by electron microscopy and by the absence of a vasodilator response to acetylcholine) reduced angiotensin I release by >90%, whereas bilateral nephrectomy 24 hours before perfusion abolished the release completely. Infusion of renin into perfused hindquarters induced sustained local angiotensin I release in the presence of an intact endothelium but not after endothelium denudation. The conversion of angiotensin I to angiotensin II was abrogated by endothelium denudation, whereas the disappearance of angiotensin II was unchanged. Endothelium denudation diminished the pressor response to angiotensin II but abolished the response to renin and angiotensin I. Expression of renin messenger RNA, investigated by reverse-transcription polymerase chain reaction using 4 different primer combinations, was not detected in up to 5 &mgr;g vascular RNA, whereas a renin signal was readily detected with 5 ng kidney RNA. The effects of endothelium destruction on Ang I formation support the notion that the endothelium mediates vascular angiotensin formation by taking up renin.


Cellular Physiology and Biochemistry | 2009

Cholesterol Depletion of the Plasma Membrane Prevents Activation of the Epithelial Sodium Channel (ENaC) by SGK1

Bettina Krueger; Silke Haerteis; Li Min Yang; Andrea Hartner; Robert Rauh; Christoph Korbmacher; Alexei Diakov

The lipid environment of the epithelial sodium channel (ENaC) and its possible association with so-called lipid rafts may be relevant to its function. The aim of our study was to confirm the association of ENaC with lipid rafts and to analyze the effect of cholesterol depletion of the plasma membrane by methyl-β-cyclodextrin (MβCD) on channel function and regulation. Using sucrose density gradient centrifugation we demonstrated that a significant portion of ENaC protein distributes to low density fractions thought to be typical lipid raft fractions. Importantly, cholesterol depletion of cell lysate by MβCD shifted ENaC to non-raft fractions of higher density. Live cell imaging demonstrated that treatment with MβCD largely reduced filipin staining over time, confirming cholesterol depletion of the plasma membrane. For electrophysiological studies intact oocytes were exposed to 20 mM MβCD for three hours. MβCD treatment had no consistent effect on baseline whole-cell ENaC currents. In addition to the typical single channel conductance of about 5 pS, subconductance states of ENaC were occasionally observed in patches from MβCD treated but not from control oocytes. Importantly, in outside-out patch clamp recordings the stimulatory effect of recombinant SGK1 in the pipette solution was essentially abolished in oocytes pretreated with MβCD. These results indicate that ENaC activation by cytosolic SGK1 is compromised by removing cholesterol from the plasma membrane. Thus, ENaC activation by SGK1 may require the presence of an intact lipid environment and/or of lipid rafts as signalling platform.


The Journal of Physiology | 2008

Aldosterone responsiveness of the epithelial sodium channel (ENaC) in colon is increased in a mouse model for Liddle's syndrome

Marko Bertog; John E. Cuffe; Sylvain Pradervand; Edith Hummler; Andrea Hartner; Markus Porst; Karl F. Hilgers; Bernard C. Rossier; Christoph Korbmacher

Liddles syndrome is an autosomal dominant form of human hypertension, caused by gain‐of‐function mutations of the epithelial sodium channel (ENaC) which is expressed in aldosterone target tissues including the distal colon. We used a mouse model for Liddles syndrome to investigate ENaC‐mediated Na+ transport in late distal colon by measuring the amiloride‐sensitive transepithelial short circuit current (ΔISC‐Ami) ex vivo. In Liddle mice maintained on a standard salt diet, ΔISC‐Ami was only slightly increased but plasma aldosterone (PAldo) was severely suppressed. Liddle mice responded to a low or a high salt diet by increasing or decreasing, respectively, their PAldo and ΔISC‐Ami. However, less aldosterone was required in Liddle animals to achieve similar or even higher Na+ transport rates than wild‐type animals. Indeed, the ability of aldosterone to stimulate ΔISC‐Ami was about threefold higher in Liddle animals than in the wild‐type controls. Application of aldosterone to colon tissue in vitro confirmed that ENaC stimulation by aldosterone was not only preserved but enhanced in Liddle mice. Aldosterone‐induced transcriptional up‐regulation of the channels β‐ and γ‐subunit (βENaC and γENaC) and of the serum‐ and glucocorticoid‐inducible kinase 1 (SGK1) was similar in colon tissue from Liddle and wild‐type animals, while aldosterone had no transcriptional effect on the α‐subunit (αENaC). Moreover, Na+ feedback regulation was largely preserved in colon tissue of Liddle animals. In conclusion, we have demonstrated that in the colon of Liddle mice, ENaC‐mediated Na+ transport is enhanced with an increased responsiveness to aldosterone. This may be pathophysiologically relevant in patients with Liddles syndrome, in particular on a high salt diet, when suppression of PAldo is likely to be insufficient to reduce Na+ absorption to an appropriate level.

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Wolfgang Rascher

University of Erlangen-Nuremberg

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Nada Cordasic

University of Erlangen-Nuremberg

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Karl F. Hilgers

University of Erlangen-Nuremberg

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Karl F. Hilgers

University of Erlangen-Nuremberg

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Kerstin Amann

University of Erlangen-Nuremberg

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Carlos Menendez-Castro

University of Erlangen-Nuremberg

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Fabian B. Fahlbusch

University of Erlangen-Nuremberg

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Roland Veelken

University of Erlangen-Nuremberg

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Bernd Klanke

University of Erlangen-Nuremberg

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Gudrun Volkert

University of Erlangen-Nuremberg

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