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Svetlana Slavic,
Dilyara Lauer,
Manuela Sommerfeld,
Ulrich Rudolf Kemnitz,
Aleksandra Grzesiak,
Manuela Trappiel, Christa Thöne-Reineke,
Johannes Baulmann,
Ludovit Paulis,
Kai Kappert,
Ulrich Kintscher,
Thomas Unger,
Elena Kaschina
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ABSTRACT: The cannabinoid receptors, CB1 and CB2, are expressed in the heart, but their role under pathological conditions remains controversial. This study examined the effect of CB1 receptor blockade on cardiovascular functions after experimental MI and in experimental metabolic syndrome. MI was induced in Wistar rats by permanent ligation of the left coronary artery. Treatment with the CB1 receptor antagonist rimonabant (10 mg/kg i.p. daily) started 7 days before or 6 h after MI and continued for 6 weeks. Haemodynamic parameters were measured via echocardiography and intracardiac Samba catheter. CB1 blockade improved systolic and diastolic heart function, decreased cardiac collagen and hydroxyproline content and down-regulated TGF-β1. Additionally, rimonabant decreased arterial stiffness, normalised QRS complex duration and reduced brain natriuretic peptide levels in serum. In primary cardiac fibroblasts, rimonabant decreased MMP-9 activity and TGF-β1 expression. Furthermore, rimonabant improved depressed systolic function of spontaneously hypertensive obese rats and reduced weight gain. Blocking of CB1 receptor with rimonabant improves cardiac functions in the early and late stages after MI, decreases arterial stiffness and reduces cardiac remodelling. Rimonabant also has cardioprotective actions in rats characterised by the metabolic syndrome. Inhibition of proteolysis and TGF-β1 expression and reduced collagen content by rimonabant may attenuate destruction of the extracellular matrix and decrease fibrosis after MI.
Journal of Molecular Medicine 05/2013; · 4.67 Impact Factor
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Pawel Namsolleck,
Francesco Boato,
Katja Schwengel,
Ludovit Paulis,
Katherine Matho,
Nathalie Geurts, Christa Thöne-Reineke,
Kristin Lucht,
Kerstin Seidel,
Anders Hallberg,
Björn Dahlöf,
Thomas Unger,
Sven Hendrix,
U Muscha Steckelings
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ABSTRACT: It is widely accepted that the angiotensin AT2-receptor (AT2R) has neuroprotective features. In the present study we tested pharmacological AT2R-stimulation as a therapeutic approach in a model of spinal cord compression injury (SCI) in mice using the novel non-peptide AT2R-agonist, Compound 21 (C21). Complementary experiments in primary neurons and organotypic cultures served to identify underlying mechanisms. Functional recovery and plasticity of corticospinal tract (CST) fibers following SCI were monitored after application of C21 (0,3mg/kg/dayi.p.) or vehicle for 4weeks. Organotypic co-culture of GFP-positive entorhinal cortices with hippocampal target tissue served to evaluate the impact of C21 on reinnervation. Neuronal differentiation, apoptosis and expression of neurotrophins were investigated in primary murine astrocytes and neuronal cells. C21 significantly improved functional recovery after SCI compared to controls, and this significantly correlated with the increased the number of CST fibers caudal to the lesion site. In vitro, C21 significantly promoted reinnervation in organotypic brain slice co-cultures (+50%) and neurite outgrowth of primary neurons (+25%). C21-induced neurite outgrowth was absent in neurons derived from AT2R-KO mice. In primary neurons, treatment with C21 further induced RNA expression of anti-apoptotic Bcl-2 (+75.7%), brain-derived neurotrophic factor (BDNF) (+53.7%), the neurotrophin receptors TrkA (+57.4%) and TrkB (+67.9%) and a marker for neurite growth, GAP43 (+103%), but not TrkC. Our data suggest that selective AT2R-stimulation improves functional recovery in experimental spinal cord injury through promotion of axonal plasticity and through neuroprotective and anti-apoptotic mechanisms. Thus, AT2R-stimulation may be considered for the development of a novel therapeutic approach for the treatment of spinal cord injury.
Neurobiology of Disease 11/2012; · 5.40 Impact Factor
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Ludovit Paulis,
Sophie T R Becker,
Kristin Lucht,
Katja Schwengel,
Svetlana Slavic,
Elena Kaschina, Christa Thöne-Reineke,
Björn Dahlöf,
Johannes Baulmann,
Thomas Unger,
U Muscha Steckelings
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ABSTRACT: Pulse wave velocity (PWV), a direct marker of arterial stiffness, is an independent cardiovascular risk factor. Although the angiotensin II type 1 receptor blockade belongs to major antihypertensive and cardioprotective therapies, less is known about the effects of long-term stimulation of the angiotensin II type 2 receptor. Previously, compound 21, a selective nonpeptide angiotensin II type 2 receptor agonist improved the outcome of myocardial infarction in rats along with anti-inflammatory properties. We investigated whether compound 21 alone or in combination with angiotensin II type 1 receptor blockade by olmesartan medoxomil could prevent PWV increase and aortic remodeling in N(ω)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension. Male adult Wistar rats (n=65) were randomly assigned to control, L-NAME, L-NAME+compound-21, L-NAME+olmesartan, and L-NAME+olmesartan+compound-21 groups and treated for 6 weeks. We observed that L-NAME hypertension was accompanied by enhanced PWV, increased wall thickness, and stiffness of the aorta, along with elevated hydroxyproline concentration. Olmesartan completely prevented hypertension, PWV and wall thickness increase, and the increase of aortic stiffness and partly prevented hydroxyproline accumulation. Compound 21 partly prevented all of these alterations, yet without concomitant prevention of blood pressure rise. Although the combination therapy with olmesartan and compound 21 led to blood pressure levels, PWV, and wall thickness comparable to olmesartan-alone-treated rats, only in the combination group was complete prevention of increased hydroxyproline deposition achieved, resulting in even more pronounced stiffness reduction. We conclude that chronic angiotensin II type 2 receptor stimulation prevented aortic stiffening and collagen accumulation without preventing hypertension in rats with inhibited NO synthase. These effects were additive to angiotensin II type 1 receptor blockade, yet without additional blood pressure-lowering effect, and they seem to be NO and blood pressure independent.
Hypertension 01/2012; 59(2):485-92. · 6.21 Impact Factor
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Kerstin Seidel,
Sebastian Kirsch,
Kristin Lucht,
Daniela Zaade,
Jana Reinemund,
Jennifer Schmitz,
Sabrina Klare,
Yaosi Li,
Jan H Schefe,
Kristin Schmerbach,
Petra Goldin-Lang,
Frank S Zollmann, Christa Thöne-Reineke,
Thomas Unger,
Heiko Funke-Kaiser
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ABSTRACT: Stroke is one of the major medical burdens in industrialized countries. Animal experiments indicate that blockade of the angiotensin AT1 receptor (AT1R) improves neurological outcome after cerebral ischemia. These protective effects are partially mediated by the angiotensin AT2 receptor (AT2R). The transcription factor promyelocytic leukemia zinc finger (PLZF) was identified as a direct adapter protein of the AT2R. Furthermore, our group was able to demonstrate that PLZF also directly binds and mediates the effects of the human (pro)renin receptor [(P)RR] which is involved in brain development. Therefore, we hypothesized that PLZF is involved in neuroprotection. Here we show that PLZF and its receptors (P)RR and AT2R exhibited an ubiquitous expression pattern in different brain regions. Furthermore, stable PLZF overexpression in human neuronal cells was able to mediate neuroprotection in a glutamate toxicity model in vitro. Consistently, PLZF mRNA and protein were downregulated on the ipsilateral side in a stroke model in vivo, whereas the neurodetrimental PLZF target genes cyclin A2 and BID were upregulated under this condition. Further analyses indicated that the neuroprotective AT2R is upregulated upon stable PLZF overexpression in cultured neuronal cells. Finally, reporter gene assays demonstrated the functionality of (P)RR promoter polymorphisms regarding basal and PLZF-induced activity.
Brain Pathology 01/2011; 21(1):31-43. · 3.99 Impact Factor
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Franziska Rompe,
Metin Artuc,
Anders Hallberg,
Mathias Alterman,
Katja Ströder, Christa Thöne-Reineke,
Anne Reichenbach,
Jens Schacherl,
Björn Dahlöf,
Michael Bader,
Natalia Alenina,
Markus Schwaninger,
Torsten Zuberbier,
Heiko Funke-Kaiser,
Cosima Schmidt,
Wolf-Hagen Schunck,
Thomas Unger,
U Muscha Steckelings
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ABSTRACT: Angiotensin II type 2 (AT(2)) receptors can be regarded as an endogenous repair system, because the AT(2) receptor is upregulated in tissue damage and mediates tissue protection. A potential therapeutic use of this system has only recently come within reach through synthesis of the first selective, orally active, nonpeptide AT(2) receptor agonist, compound 21 (C21; dissociation constant for AT(2) receptor: 0.4 nM; dissociation constant for angiotensin II type 1 receptor: >10,000 nM). This study tested AT(2) receptor stimulation with C21 as a potential future therapeutic approach for the inhibition of proinflammatory cytokines and of nuclear factor kappaB. C21 dose-dependently (1 nM to 1 micromol/L) reduced tumor necrosis factor-alpha-induced interleukin 6 levels in primary human and murine dermal fibroblasts. AT(2) receptor specificity was controlled for by inhibition with the AT(2) receptor antagonist PD123319 and by the absence of effects in AT(2) receptor-deficient cells. AT(2) receptor-coupled signaling leading to reduced interleukin 6 levels involved inhibition of nuclear factor kappaB, activation of protein phosphatases, and synthesis of epoxyeicosatrienoic acid. Inhibition of interleukin 6 promoter activity by C21 was comparable in strength to inhibition by hydrocortisone. C21 also reduced monocyte chemoattractant protein 1 and tumor necrosis factor-alpha in vitro and in bleomycin-induced toxic cutaneous inflammation in vivo. This study is the first to show the anti-inflammatory effects of direct AT(2) receptor stimulation in vitro and in vivo by the orally active, nonpeptide AT(2) receptor agonist C21. These data suggest that pharmacological AT(2) receptor stimulation may be an orally applicable future therapeutic approach in pathological settings requiring the reduction of interleukin 6 or inhibition of nuclear factor kappaB.
Hypertension 02/2010; 55(4):924-31. · 6.21 Impact Factor
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Christa Thöne-Reineke,
Christian Neumann,
Pawel Namsolleck,
Kristin Schmerbach,
Maxim Krikov,
Jan H Schefe,
Kristin Lucht,
Heide Hörtnagl,
Michael Godes,
Susanne Müller,
Kay Rumschüssel,
Heiko Funke-Kaiser,
Arno Villringer,
U Muscha Steckelings,
Thomas Unger
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ABSTRACT: Ceftriaxone has been reported to reduce neuronal damage in amyotrophic lateral sclerosis and in an in-vitro model of neuronal ischaemia through increased expression and activity of the glutamate transporter, GLT1. We tested the effects of ceftriaxone on mortality, neurological outcome, and infarct size in experimental stroke in rats and looked for underlying mechanisms.
Male normotensive Wistar rats received ceftriaxone (200 mg/kg intraperitoneal) as a single injection 90 min after middle cerebral artery occlusion (90 min with reperfusion). Forty-eight hours after middle cerebral artery occlusion, infarct size (MRI) and neurological deficits were estimated. GLT1 expression was determined by real time RT-PCR, immunoblotting and promoter reporter assay, astrocyte GLT1 activity by measuring glutamate uptake. Bacterial load in various organs was measured by real time RT-PCR, neurotrophins and IL-6 by immunoblotting.
Ceftriaxone dramatically reduced early (24-h) mortality from 34.5% (vehicle treatment, n = 29) to 0% (P < 0.01, n = 19). In a subgroup, followed up for 4 weeks, mortality persisted at 0%. Ceftriaxone strongly tended to reduce infarct size, it significantly improved neuronal survival within the penumbra, reduced neurological deficits (P < 0.001) and led to an upregulation of neurotrophins (P < 0.01) in the peri-infarct zone. Ceftriaxone did not increase GLT1 expression, but increased GLT1 activity (P < 0.05).
Ceftriaxone causes a significant reduction in acute stroke mortality in a poststroke treatment regimen in animal studies. Improved neurological performance and survival may be due to neuroprotection by activation of GLT1 and a stimulation of neurotrophins resulting in an increased number of surviving neurons in the penumbra.
Journal of Hypertension 01/2009; 26(12):2426-35. · 4.02 Impact Factor
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ABSTRACT: The pathways leading to salt-sensitive hypertension and renal damage in rescued ETB receptor-deficient (ETBRd) rats are still unknown. The objective of the study was therefore to identify modifications of urinary peptide and protein expression in ETBRd rats (n = 9) and wild-type controls (n = 6) using SDS - polyacrylamide gel electrophoresis (SDS-PAGE) and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology. Glomerular filtration rate, glomerulosclerosis, and tubulointerstitial fibrosis did not differ between the groups. ETBRd rats showed slightly higher blood pressure (p < 0.001), media/lumen ratio of intrarenal arteries (p < 0.01), and albuminuria (p < 0.01). SDS-PAGE confirmed albuminuria, but showed no differences in the urinary excretion of low molecular weight proteins (<60 kDa). SELDI-TOF-MS profiling revealed 9 proteomic features at molecular masses (Da) of 2720, 2980, 3130, 3345, 6466, 6682, 8550, 18 729, and 37 492, which were significantly elevated (p < 0.02) in urine of ETBRd rats. The results demonstrate that, independent of structural changes in the kidneys, ETB-receptor deficiency causes specific differences in urinary peptide and protein excretion. SELDI-TOF-MS may be a valuable tool for the characterization of urinary biomarkers helping to uncover the mechanism of ETBR action in the kidney.
Canadian Journal of Physiology and Pharmacology 09/2008; 86(8):566-70. · 1.95 Impact Factor
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Thiemo Pfab, Christa Thöne-Reineke,
Franziska Theilig,
Ines Lange,
Henning Witt,
Christiane Maser-Gluth,
Michael Bader,
Johannes-Peter Stasch,
Patricia Ruiz,
Sebastian Bachmann,
Masashi Yanagisawa,
Berthold Hocher
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ABSTRACT: The endothelin (ET) system has been implicated in the pathogenesis of diabetic nephropathy. The role of the ET-B receptor (ETBR) is still unclear. The effect of ETBR deficiency on the progression of diabetic nephropathy in a streptozotocin model was analyzed in four groups: (1) Homozygous ETBR-deficient (ETBRd) diabetic rats, (2) ETBRd rats, (3) diabetic controls, and (4) wild-type controls. BP and kidney function were measured for 10 wk, followed by biochemical and histologic analysis of the kidneys. The study demonstrates that ETBRd diabetic rats on a normal-sodium diet develop severe hypertension, albuminuria, and a mild reduction of creatinine clearance. The strong BP rise seems not to be caused by activation of the renin-angiotensin-aldosterone system or by suppression of the nitric oxide system. Elevated plasma ET-1, possibly reflecting a reduced ETBR-dependent clearance, seems to cause the severe hypertension via the ETA receptor. The results do not support the hypothesis that a reduction of ETBR activity inhibits the progression of diabetic nephropathy. The study demonstrates for the first time that the combination of diabetes and ETBR deficiency causes severe low-renin hypertension with progressive renal failure.
Journal of the American Society of Nephrology 05/2006; 17(4):1082-9. · 9.66 Impact Factor
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ABSTRACT: Stroke is a burden of modern civilization, causing death and disability. Nowadays it is universally accepted that inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors or angiotensin II type 1 (AT1) receptor blockers (ARBs) can effectively decrease the incidence of stroke in patients at risk. Here, we summarize current knowledge concerning the molecular mechanisms of the beneficial effects of inhibition of the renin-angiotensin system in stroke, with an emphasis on mechanisms beyond blood pressure reduction; in particular, neuroprotection. All major clinical studies comparing the effectiveness of ARBs with placebo or other blood pressure decreasing drugs in stroke are mentioned and commented on. These clinical data are complemented by data from a selection of animal experiments pivotal for the understanding of neuroprotective actions of ARBs. Clinical studies have shown that ARBs can be superior to other antihypertensive drugs in the prevention of stroke, even if there are no differences in blood pressures. Findings from animal experiments suggest that the underlying mechanisms include not just inhibition of the detrimental peripheral and central actions of angiotensin II mediated by AT1-receptors, but also stimulation of unopposed angiotensin II type 2 (AT2) receptors that are upregulated in the area of ischaemia. ARBs have been proven to be effective in the prevention of stroke via mechanisms that are both dependent on and independent of the antihypertensive abilities of the drugs.
Journal of hypertension. Supplement: official journal of the International Society of Hypertension 04/2006; 24(1):S115-21.
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Andreas Patzak,
Julia Bontscho,
Enyin Lai,
Eckehardt Kupsch,
Angela Skalweit,
Claus-Michael Richter,
Mathias Zimmermann, Christa Thöne-Reineke,
Olaf Joehren,
Michael Godes,
Andreas Steege,
Berthold Hocher
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ABSTRACT: Although endothelin I (ET-1) is a very potent vasoconstrictor, ET-1 transgenic (ET-1 tg) mice are not hypertensive. This might be due to higher bioavailability of nitric oxide (NO) in ET-1 tg, which counteracts the effect of vasoconstrictors. We hypothesized lower angiotensin II (Ang II) sensitivity of afferent arterioles in ET-1 tg.
Afferent arterioles were manually dissected and microperfused. Changes of the luminal diameter due to application of vasoactive substances were used for assessment of the reactivity of afferent arterioles. We investigated the effect of L-NAME, an unspecific NO synthase inhibitor, on basal tone, and the sensitivity of afferent arterioles to Ang II with and without pre-treatment with L-NAME. The renin-angiotensin-system was characterized by expression analysis of angiotensin-receptors and renin at the mRNA level.
L-NAME reduced afferent arterioles diameters similarly in ET-1 tg and wild-types (WT). Ang II sensitivity determined by calculation of EC50 for Ang II was less in ET-1 tg compared with WT (P<0.05). Ang II reduced luminal diameters to a lesser extent in ET-1 tg compared to WT (P<0.05). After pre-treatment with L-NAME, Ang II sensitivity and maximum constriction of afferent arterioles were similar in ET-1 tg and WT. The expression of renin- and Ang II-receptor-mRNA in the kidney did not differ between either group.
The loss of differences in the maximum constriction and Ang II sensitivity of afferent arterioles between ET-1 tg and WT in the absence of NO suggests pronounced NO effects in afferent arterioles of ET-1 tg. This might contribute to the maintenance of normal renal arteriolar tone in ET-1 tg mice.
Nephrology Dialysis Transplantation 12/2005; 20(12):2681-9. · 3.40 Impact Factor
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ABSTRACT: The adipose-specific protein adiponectin has been recently discovered to improve insulin sensitivity. Angiotensin type-1 receptor (AT1R) blockers (ARBs) reduce the incidence of type 2 diabetes mellitus by mostly unknown molecular mechanisms. To identify new antidiabetic mechanisms of ARBs, we studied the regulation of adiponectin by angiotensin II (Ang II) and different ARBs in murine 3T3-L1 adipocytes and obese Zucker rats. Adiponectin protein expression was markedly stimulated by Ang II (5 nmol/L), which was inhibited by blockade of the AT2R, and further enhanced by the ARB irbesartan. Irbesartan-mediated adiponectin upregulation started beyond the concentrations needed for AT1R blockade and was also present in the absence of Ang II, implicating an AT1R-independent mechanism of action. Recently, certain ARBs (irbesartan, telmisartan) were identified as ligands of the peroxisome proliferator-activated receptor (PPAR)gamma. Telmisartan also stimulated adiponectin protein expression, whereas the non-PPARgamma-activating ARB eprosartan had no effect. Blockade of PPARgamma activation by the PPARgamma antagonist GW9662 markedly inhibited irbesartan-induced adiponectin expression. Cognate mRNA levels of adiponectin were not affected by ARBs. Kinetic studies using the protein synthesis inhibitor cycloheximide showed that irbesartan prevented the cellular depletion of adiponectin protein. Finally, administration of irbesartan to obese Zucker rats improved insulin sensitivity and attenuated adiponectin serum depletion. The present study demonstrates that AT2R activation and certain ARBs induce adiponectin in adipocytes, which was associated with an improvement of parameters of insulin sensitivity in vivo. ARB-induced adiponectin stimulation is likely to be mediated via PPARgamma activation involving a post-transcriptional mechanism.
Hypertension 08/2005; 46(1):137-43. · 6.21 Impact Factor
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ABSTRACT: Stroke is one of the leading causes of invalidism and death in the industrialized world. Among others, the renin- angiotensin system (RAS) has been implicated in the pathogenesis and outcome of ischemic events, including stroke. Angiotensin II (Ang II), the major effector peptide of the RAS, exerts most of its well-defined physiologic and pathophysiologic actions, including those on the central and peripheral nervous system, through its Ang II type 1 (AT1) receptor subtype. This receptor not only contributes to stroke-related pathologic mechanisms (eg, hypertension, atherothrombosis, and cardiac hypertrophy) but also may be involved in postischemic damage to the brain. However, it has also been demonstrated that Ang II, via its AT2 receptor subtype, accelerates neuronal tissue regeneration after injury. In this article, we review the experimental evidence supporting the notion that blockade of brain AT1 receptors can be beneficial with respect to stroke incidence and outcome. We further delineate how AT2 receptors could be involved in neuronal regeneration following brain injury, such as stroke. In doing so, we also attempt to shed some light on the mechanisms by which AT1 receptor blockers, which leave the AT2 receptor unopposed, might exert protective actions in brain ischemia.
Current Hypertension Reports 09/2004; 6(4):257-66. · 2.50 Impact Factor
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ABSTRACT: Apoptosis plays a role in the regulation of heart mass and architecture, and might contribute to the cardiac remodelling seen in renovascular hypertension. It is not known whether the beneficial effects of angiotensin-converting enzyme (ACE) inhibition or calcium channel blockade on cardiac remodelling are linked to the modulation of apoptosis. To test this hypothesis, we established four groups of rats: (i) sham-operated controls, (ii) a group that underwent the two-kidney/one-clip (2K1C) procedure, (iii) a group with 2K1C treated for 12 weeks with quinapril (6 mg x day(-1) x kg(-1)), and (iv) a group with 2K1C treated for 12 weeks with diltiazem (24 mg x day(-1) x kg(-1)). Treatment started 2 weeks after clipping. Systolic blood pressure was reduced to a similar extent by quinapril and diltiazem (2K1C, 223+/-19 mmHg; 2K1C+quinapril, 149+/-15 mmHg; 2K1C+diltiazem, 160+/-40 mmHg; both P <0.01 compared with 2K1C alone). Left ventricular weight, interstitial fibrosis and perivascular fibrosis were reduced significantly by both drugs. The apoptotic index (apoptotic cells/total cell number) was increased 21.6-fold (P <0.01) after quinapril treatment as compared with the 2K1C group, but was not affected by calcium channel blockade. In conclusion, our study demonstrates that ACE inhibition, in contrast with calcium channel blockade, may cause regression of cardiac hypertrophy/remodelling in 2K1C renovascular hypertensive rats through enhanced apoptosis.
Clinical Science 01/2003; 104(1):79-85. · 4.61 Impact Factor
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ABSTRACT: Endothelin-1 (ET-1) is a potent pro-fibrotic growth factor. However, little is known about its specific effects on the synthesis of matrix proteins in vivo. We used male 12-month-old ET-1 transgenic mice characterized by transgene expression in the kidney and (to a lesser extent) in the heart. Global cardiac and renal matrix protein synthesis was analysed after Sirius Red and periodate-Schiff staining. Specific expression of collagen types I, III and IV, laminin and fibronectin was examined using immunohistochemistry followed by computer-aided image analysis. Analysis of blood pressure revealed that mean arterial blood pressure was similar in ET-1 transgenic mice and controls. The total cardiac matrix protein content was increased in the myocardium of ET-1 transgenic mice. Analysis of specific cardiac matrix proteins showed increased cardiac expression of collagen type III (+211%; P<0.001) and laminin (+128%; P<0.01) in transgenic mice. The expression of collagen types I and IV and fibronectin was not altered. Global analysis of renal matrix proteins confirmed earlier studies showing pronounced interstitial fibrosis and glomerulosclerosis. Laminin expression was markedly increased in the glomerula (+152%; P<0.01) and even more so in the interstitium (+211%; P<0.001), whereas expression of collagen type III was reduced in glomerula (-48%; P<0.01) and interstitial tissue (-55%; P<0.01) of ET-1 transgenic mice. In conclusion, a primary overexpression of ET-1 does not cause uniformly enhanced synthesis of matrix proteins. In contrast, the effects of ET-1 on the matrix protein pattern is tissue-specific. The major renal and cardiac alterations in matrix proteins induced by ET-1 is a marked enhancement of laminin expression.
Clinical Science 08/2002; 103 Suppl 48:39S-43S. · 4.61 Impact Factor
