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Sham-operated Rats (sham-operated + rat)
Selected AbstractsLosartan decreases vasopressin-mediated cAMP accumulation in the thick ascending limb of the loop of Henle in rats with congestive heart failureACTA PHYSIOLOGICA, Issue 4 2007M. Torp Abstract Introduction:, Vasopressin (AVP) stimulates sodium reabsorption and Na,K,2Cl-cotransporter (NKCC2) protein level in the thick ascending limb (TAL) of Henle's loop in rats. Rats with congestive heart failure (CHF) have increased protein level of NKCC2, which can be normalized by angiotensin II receptor type-1 (AT1) blockade with losartan. Aim:, In this study, we investigated whether CHF rats displayed changes in AVP stimulated cAMP formation in the TAL and examined the role of AT1 receptor blockade on this system. Method:, CHF was induced by ligation of the left anterior descending coronary artery (LAD). SHAM-operated rats were used as controls. Half of the rats were treated with losartan (10 mg kg day,1 i.p.). Results:, CHF rats were characterized by increased left ventricular end diastolic pressure. Measurement of cAMP in isolated outer medullary TAL showed that both basal and AVP (10,6 m) stimulated cAMP levels were significantly increased in CHF rats (25.52 ± 4.49 pmol cAMP ,g,1 protein, P < 0.05) compared to Sham rats (8.13 ± 1.14 pmol cAMP ,g,1 protein), P < 0.05). Losartan significantly reduced the basal level of cAMP in CHF rats (CHF: 12.56 ± 1.93 fmol ,g,1 protein vs. Los-CHF: 7.49 ± 1.08, P < 0.05), but not in Sham rats (SHAM: 4.66 ± 0.59 vs. Los-SHAM: 4.75 ± 0.71). AVP-mediated cAMP accumulation was absent in both groups treated with losartan (Los-SHAM: 4.75 ± 0.71 and Los-CHF: 7.49 ± 1.08). Conclusion:, The results indicate that the increased NKCC2 protein level in the mTAL from CHF rats is associated with increased cAMP accumulation in this segment. Furthermore, the finding that AT1 receptor blockade prevents AVP-mediated cAMP accumulation in both SHAM and CHF rats suggests an interaction between angiotensin II and AVP in regulation of mTAL Na reabsorption. [source] The antiepileptic drug levetiracetam selectively modifies kindling-induced alterations in gene expression in the temporal lobe of ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2004Jessie Gu Abstract Gene expression profiling by microarrays is a powerful tool for identification of genes that may encode key proteins involved in molecular mechanisms underlying epileptogenesis. Using the Affymetrix oligonucleotide microarray, we have surveyed the expression levels of more than 26,000 genes and expressed sequence tags (ESTs) in the amygdala-kindling model of temporal lobe epilepsy. Furthermore, the effect of the antiepileptic drug levetiracetam (LEV) on kindling-induced alterations of gene expression was studied. Treatment of rats with LEV during kindling acquisition significantly suppressed kindling development. For gene expression profiling, six groups of rats were included in the present study: (i) and (ii) sham-operated rats treated with saline or LEV; (iii) and (iv) electrode-implanted but non-kindled rats treated with saline or LEV; (v) and (vi) kindled rats treated with saline or LEV. Treatment was terminated after 11 or 12 daily amygdala stimulations, when all vehicle-treated rats had reached kindling criterion, i.e. a stage 5 seizure. Twenty-four hours later, the ipsilateral temporal lobe was dissected for mRNA preparation. Six temporal lobe preparations from each group were analysed for differential gene expression. In control (non-kindled) rats, LEV treatment was devoid of any significant effect on gene expression. In saline-treated kindled rats, a large number of genes were observed to display mRNA expression alterations compared with non-kindled rats. LEV treatment induced marked effects on gene expression from kindled rats. Previously described epilepsy-related genes, such as neuropeptide Y (NPY), thyrotropin-releasing hormone (TRH) and glial fibrillary acidic protein (GFAP) were confirmed to be up-regulated by kindling and partially normalized by LEV treatment. Real-time quantitative polymerase chain reaction confirmed NPY, TRH and GFAP expression data from chip experiments. Furthermore, a number of novel genes were identified from the gene chip experiments. A subgroup of these genes demonstrated correlation between expression changes and kindled phenotype measurements. In summary, this study identified many genes with potentially important roles in epileptogenesis and highlighted several important issues in using the gene chip technology for the study of animal models of CNS disorders. [source] O2 -sensing after carotid chemodenervation: hypoxic ventilatory responsiveness and upregulation of tyrosine hydroxylase mRNA in brainstem catecholaminergic cellsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2000Jean-Christophe Roux Abstract Ventilatory responses to acute and long-term hypoxia are classically triggered by carotid chemoreceptors. The chemosensory inputs are carried within the carotid sinus nerve to the nucleus tractus solitarius and the brainstem respiratory centres. To investigate whether hypoxia acts directly on brainstem neurons or secondarily via carotid body inputs, we tested the ventilatory responses to acute and long-term hypoxia in rats with bilaterally transected carotid sinus nerves and in sham-operated rats. Because brainstem catecholaminergic neurons are part of the chemoreflex pathway, the ventilatory response to hypoxia was studied in association with the expression of tyrosine hydroxylase (TH). TH mRNA levels were assessed in the brainstem by in situ hybridization and hypoxic ventilatory responses were measured in vivo by plethysmography. After long-term hypoxia, TH mRNA levels in the nucleus tractus solitarius and ventrolateral medulla increased similarly in chemodenervated and sham-operated rats. Ventilatory acclimatization to hypoxia developed in chemodenervated rats, but to a lesser extent than in sham-operated rats. Ventilatory response to acute hypoxia, which was initially low in chemodenervated rats, was fully restored within 21 days in long-term hypoxic rats, as well as in normoxic animals which do not overexpress TH. Therefore, activation of brainstem catecholaminergic neurons and ventilatory adjustments to hypoxia occurred independently of carotid chemosensory inputs. O2 -sensing mechanisms unmasked by carotid chemodenervation triggered two ventilatory adjustments: (i) a partial acclimatization to long-term hypoxia associated with TH upregulation; (ii) a complete restoration of acute hypoxic responsivity independent of TH upregulation. [source] Increased responsivity of glutamate release from the substantia nigra pars reticulata to striatal NMDA receptor blockade in a model of Parkinson's disease.EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2000A dual probe microdialysis study in hemiparkinsonian rats Abstract Dual probe microdialysis was employed in freely moving 6-hydroxydopamine (6-OHDA) hemilesioned rats to investigate the effects of blockade of N-methyl-D-aspartate (NMDA) receptors in the dorsolateral striatum on glutamate (Glu) release from the ipsilateral substantia nigra pars reticulata (SNr). Perfusion for 60 min with the NMDA antagonist dizocilpine (0.1 and 1 ,m) in the dopamine (DA)-denervated striatum stimulated nigral Glu release (peak effect of 139 ± 7% and 138 ± 9%, respectively). The lower (0.01 ,m) and higher (10 ,m) concentrations were ineffective. In sham-operated rats, dizocilpine failed to affect nigral Glu release up to 1 ,m but induced a prolonged stimulation at 10 ,m (153 ± 9% at the end of perfusion). The present results show that DA-deficiency in the striatum of hemiparkinsonian rats is associated with increased responsivity of nigral Glu release to striatal NMDA receptor blockade. This suggests that changes of NMDA receptor mediated control of the striatofugal pathways occur during Parkinson's disease (PD). [source] p53 may positively regulate hepatocyte proliferation in ratsHEPATOLOGY, Issue 2 2002Yukiko Inoue p53, known as a tumor suppressor gene, is a transcription factor that regulates various cellular functions. Recently, several growth factor gene promoters, including that of transforming growth factor , (TGF-,), were shown to be direct targets of p53-mediated transcription. Hepatic p53 mRNA is up-regulated during liver regeneration in rats. The aim of this study is to examine the role of p53 in hepatocyte proliferation. p53 protein levels were examined in rat hepatocytes cultured in the medium containing hepatocyte growth factor (HGF). p53 levels began to increase after 6 hours of incubation, reached a maximum at 18 hours, and decreased thereafter. DNA synthesis increased at 12 hours and peaked at 30 hours. When hepatocytes were incubated with p53 antisense oligonucleotide in addition to HGF, increases of p53 and TGF-, levels were suppressed, and DNA synthesis was reduced. The increases of TGF-, levels and DNA synthesis were also suppressed by a chemical inhibitor of p53, pifithrin-,. In rats after two-thirds partial hepatectomy, hepatic p53 increased and reached maximal levels around 16 hours when hepatic HGF levels have been shown to reach a maximum followed by an increase in hepatic TGF-, levels or hepatocyte proliferation. In contrast, sham-operated rats showed minor elevations of hepatic p53 levels. In conclusion, p53 production is stimulated by HGF and may contribute to the proliferation of rat hepatocytes. Considering previous findings indicating the importance of endogenous TGF-, for the proliferation of hepatocytes stimulated by HGF, TGF-, might play a role in HGF-p53 mediated hepatocyte proliferation. [source] Entorhinal cortex lesions disrupt fear conditioning to background context but spare fear conditioning to a tone in the ratHIPPOCAMPUS, Issue 2 2006M. Majchrzak Abstract Recent studies have shown that the integrity of the entorhinal cortex (EC) is not required for simple contextual conditioning. In background contextual conditioning, i.e., when a phasic cue is present during training, the involvement of the EC is still a matter of debate. Therefore, the present work further examines whether the EC is required for background contextual conditioning using a tone as the phasic cue. Rats sustaining either excitotoxic lesions of the EC or sham-lesions were trained with one of two procedures differing with respect to the predictive value of the tone: a paired procedure in which the tone perfectly predicts shock occurrence and overshadows context, and an unpaired procedure in which the predictive value of the tone is reduced. Conditioned fear was assessed by freezing responses during conditioning, reexposure to the training context, and reexposure to the tone in a new context. Postshock freezing was reduced in rats with entorhinal lesions. In all rats trained with the paired procedure, freezing to the context was low and freezing to the tone was high, suggesting that the tone has overshadowed the context during the conditioning session. The reverse pattern was observed with the unpaired procedure in sham-operated rats. In rats with entorhinal lesions trained with the unpaired procedure, freezing responses to the context was markedly reduced. In a new context, however, entorhinal-lesioned rats showed higher freezing scores than those of sham-lesioned rats. Freezing to the tone was unaffected by the lesion irrespective of the tone's predictive value. As a whole, these results support the notion that the EC is required for normal background contextual freezing. © 2005 Wiley-Liss, Inc. [source] Autologous bone-marrow-derived mesenchymal stem cell transplantation into injured rat urethral sphincterINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2010Yoshiaki Kinebuchi Objectives: To evaluate the functional and histological recovery by autologous bone-marrow-derived mesenchymal stem cell (BMSC) transplantation into injured rat urethral sphincters. Methods: BMSC were harvested from female Sprague,Dawley retired breeder rats for later transplantation. The cells were cultured, and transfected with the green fluorescence protein gene. The urethral sphincters were injured by combined urethrolysis and cardiotoxin injection. One week after injury, the cultured BMSC were injected autologously into the periurethral tissues. Controls included sham-operated rats and injured rats injected with cell-free medium (CFM). Abdominal leak point pressures (LPP) were measured before and after surgery during the following 13 weeks. The urethras were then retrieved for histological evaluation. The presence of green-fluorescence-protein-labeled cells and the regeneration of skeletal muscles, smooth muscles, and peripheral nerves were evaluated by immunohistochemical staining. Results: LPP was significantly reduced in the injured rats. It increased gradually after transplantation, but there was no significant difference between the BMSC and CFM groups. In the BMSC group, transplanted cells survived and differentiated into striated muscle cells and peripheral nerve cells. The proportions of skeletal muscle cells and peripheral nerves in the urethra were significantly greater in the BMSC group compared to the CFM group. Conclusions: Despite a clear trend towards recovery of LPP in BMSC-transplanted urethras, no significant effect was detected. Further study is required for clinical applications for the treatment of stress urinary incontinence. [source] Global analysis of gene expression profiles in ileum in a rat bladder augmentation model using cDNA microarraysINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2004HIDEAKI MIYAKE Abstract Background: The objective of the present study was to globally characterize the changes in the gene expression profile in the ileum after long-term urine exposure in a rat ileal augmented bladder model using cDNA microarrays. Methods: Bladder augmentation using the ileum was performed in female 8-week-old rats. The ileal epithelia used for bladder augmentation were harvested 1 and 3 months postoperatively and changes in the gene expression in these tissues were compared with that of intact ileal epithelia from sham-operated rats using cDNA microarrays consisting of 1176 rat genes. Results: Marked changes in gene expression in the ileum used for bladder augmentation were observed for 30 genes (16 up-regulated and 14 down-regulated genes). The differentially expressed genes include those associated with signal transduction, cell adhesion and stress response. Subsequent evaluation of changes in two randomly selected genes from the 30 differentially expressed genes by semiquantitative reverse transcription-polymerase chain reaction demonstrated the reliability of the present cDNA microarray analyses. Conclusion: The present experiments identified an extensive list of genes differentially expressed in the ileum after bladder augmentation, providing valuable information for the pathophysiological assessment of patients who undergo urinary reconstruction and representing a source of novel targets for treating complications after urinary diversion. [source] Collagen Metabolism Is Markedly Altered in the Hypertrophic Cartilage of Growth Plates from Rats with Growth Impairment Secondary to Chronic Renal FailureJOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2001Jesús Álvarez Abstract Skeletal growth depends on growth plate cartilage activity, in which matrix synthesis by chondrocytes is one of the major processes contributing to the final length of a bone. On this basis, the present work was undertaken to ascertain if growth impairment secondary to chronic renal insufficiency is associated with disturbances of the extracellular matrix (ECM) of the growth plate. By combining stereological and in situ hybridization techniques, we examined the expression patterns of types II and X collagens and collagenase-3 in tibial growth plates of rats made uremic by subtotal nephrectomy (NX) in comparison with those of sham-operated rats fed ad libitum (SAL) and sham-operated rats pair-fed with NX (SPF). NX rats were severely uremic, as shown by markedly elevated serum concentrations of urea nitrogen, and growth retarded, as shown by significantly decreased longitudinal bone growth rates. NX rats showed disturbances in the normal pattern of chondrocyte differentiation and in the rates and degree of substitution of hypertrophic cartilage with bone, which resulted in accumulation of cartilage at the hypertrophic zone. These changes were associated with an overall decrease in the expression of types II and X collagens, which was especially marked in the abnormally extended zone of the hypertrophic cartilage. Unlike collagen, the expression of collagenase-3 was not disturbed severely. Electron microscopic analysis proved that changes in gene expression were coupled to alterations in the mineralization as well as in the collagen fibril architecture at the hypertrophic cartilage. Because the composition and structure of the ECM have a critical role in regulating the behavior of the growth plate chondrocytes, results obtained are consistent with the hypothesis that alteration of collagen metabolism in these cells could be a key process underlying growth retardation in uremia. [source] Age and ovariectomy impair both the normalization of mechanical properties and the accretion of mineral by the fracture callus in ratsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2001Ralph A. Meyer Jr. The impact of age and ovariectomy on the healing of femoral fractures was studied in three groups of female rats at 8, 32 and 50 weeks of age at fracture. In the two older groups, the rats had been subjected to ovariectomy or sham surgery at random at 26 weeks of age. At fracture, all rats received unilateral intramedullary pinning of one femur and a middiaphyseal fracture. Rigidity and breaking load of the femora were evaluated at varying times up to 24 weeks after fracture induction by three-point bending to failure. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. In the youngest group, 8-week-old female rats regained normal femoral rigidity and breaking load by 4 weeks after fracture. They exceeded normal contralateral values by 8 weeks after fracture. In the middle group, at 32 weeks of age, fractures were induced, and the femora were harvested at 6 and 12 weeks after fracture. At 6 weeks after fracture there was partial restoration of rigidity and breaking load. At 12 weeks after fracture, only the sham-operated rats had regained normal biomechanical values in their fractured femora, while the fractured femora of the ovariectomized rats remained significantly lower in both rigidity and breaking load. In contrast, for the oldest group of rats, 50 weeks old at fracture, neither sham-operated nor ovariectomized rats regained normal rigidity or breaking load in their fractured femora within the 24 weeks in which they were studied. In all fractured bones, there was a significant increase in BMD over the contralateral intact femora due to the increased bone tissue and bone mineral in the fracture callus. Ovariectomy significantly reduced the BMD of the intact femora and also reduced the gain in BMD by the fractured femora. In conclusion, age and ovariectomy significantly impair the process of fracture healing in female rats as judged by measurements of rigidity and breaking load in three-point bending and by accretion of mineral into the fracture callus. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Enhanced bioavailability of a new thiazolidine derivative FPFS-410, an antidiabetic and lipid-lowering drug, after oral administration of its hydroxypropyl-,-cyclodextrin complex to bile duct-cannulated ratsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2006Takumi Hara Abstract The effect of bile acids on bioavailability of FPFS-410 (2-(N -Cyanoimino)-5-{(E)-4-styrylbenzylidene}-4-oxothiazolidine) after oral administration of the drug and its 2-hydroxypropyl-,-cyclodextrin (HP-,-CyD) complex was investigated. The complexation with HP-,-CyD increased the oral bioavailability of FPFS-410 in normal rats in a HP-,-CyD concentration-dependent manner, compared with that of drug alone. In bile duct-cannulated rats, bile acid concentrations in pylic serum and biliary were decreased to 18% and 14% of sham-operated rats, respectively. After oral administration of the HP-,-CyD complex, the plasma levels of FPFS-410 were lower in bile duct-cannulated rats than in sham-operated rats up to 1 h, however, this order reversed from 2 to 12 h. The plasma levels of M1, a dominant metabolite of FPFS-410 in rats, significantly decreased until 2 h after administration of the complex in bile duct-cannulated rats, compared with in sham-operated rats. Bioconversion of FPFS-410 to M1 and CYP3A2 expression in the liver was markedly lowered by bile duct-cannulation. Bile duct-cannulation did not, however, affect the serum levels of estradiol. These results suggest that bile acids have a pivotal role for bioavailability of FPFS-410 after oral administration of the FPFS-410 complex with HP-,-CyD through CYP3A2 activity in liver of rats. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1771,1782, 2006 [source] D-003 does not possess oestrogenic potential in-vivo: findings of the uterotrophic assayJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2007Miriam Noa D-003 is a mixture of long-chain fatty acids purified from sugarcane wax that inhibits both cholesterol synthesis prior to mevalonate formation, and lipid peroxidation. D-003 has been shown to prevent bone loss and bone resorption in ovariectomized rats, and significantly improves bone resorption markers in postmenopausal women with reduced bone mineral density. As hormone-replacement therapy, D-003 displays cholesterol-lowering and anti-resorptive effects. We have studied its potential oestrogenic activity in-vivo using the uterotrophic assay. Rats were randomly distributed into five groups: a sham-operated group and four groups of ovariectomized rats, one treated with vehicle, one with D-003 (50 mg kg,1), one with oestradiol benzoate (30 ,g kg,1) and one with D-003 (50 mg kg,1) plus oestradiol benzoate (30 ,g kg,1). Treatments were administered for 14 days. Ovariectomy decreased the values of relative uterus weight, epithelium cell height and endometrial thickness compared with sham-operated rats, and these effects were all significantly reduced with oestradiol benzoate, but not with D-003. Concurrent administration of D-003 and oestradiol benzoate had statistically similar effects on all variables as oestradiol benzoate alone. In conclusions, D-003 orally given at 50 mg kg,1, a dose that prevents bone loss and bone resorption in ovariectomized rats, did not display oestrogenic/anti-oestrogenic activity in-vivo, as assessed in the uterotrophic assay. [source] Roles of nocturnal melatonin and the pineal gland in modulation of water-immersion restraint stress-induced gastric mucosal lesions in ratsJOURNAL OF PINEAL RESEARCH, Issue 2 2001Migusa Otsuka The roles of melatonin and the pineal gland in the circadian variation of water-immersion restraint stress-induced gastric mucosal lesions in rats were investigated. Fasted rats were subjected to water-immersion restraint stress during both the diurnal and nocturnal phases of a light:dark cycle. Pinealectomized and sham-operated rats were also subjected to water-immersion restraint stress at night. The lesion area after 4 hr of stress during the dark phase was significantly lower than in light-phase controls. Pinealectomy increased the lesion area in the dark phase, compared to the sham operation, but this effect was counteracted by intracisternal melatonin preadministration at a dose of 100 ng/rat. Melatonin concentrations in control rats during the light phase were significantly increased 4 hr after water-immersion restraint stress. In contrast, melatonin concentrations 4 hr after water-immersion restraint stress in the dark phase were significantly depressed compared with the control levels at the corresponding time. Melatonin levels after stress exposure were markedly decreased in pinealectomized rats as compared with sham-operated rats. These results suggest that circadian rhythm has an important role in the formation of stress-induced gastric mucosal lesions in rats and that melatonin responses to water-immersion restraint stress differ between day and night. The pineal gland modulates the stress response and melatonin contributes to gastric protection via a mechanism involving the central nervous system. [source] Hypoandrogenism related to early skin wound healing resistance in ratsANDROLOGIA, Issue 2 2010A. Petroianu Summary The purpose of this study was to verify the effect of testosterone depletion on healing of surgical skin wounds at different ages and post-operative periods. Forty-four Wistar male rats were divided into four groups: Group 1Y (n = 11) , young control, sham-operated rats (30-day old); Group 1A (n = 10) , adult control, sham-operated rats (3 to 4-month old); Group 2Y (n = 10) , young rats after bilateral orchiectomy; and Group 2A (n = 11) , adult rats after bilateral orchiectomy. After 6 months, a linear incision was performed on the dorsal region of the animals. The resistance of the wound healing was measured in a skin fragment using a tensiometer, on the 7th and 21st post-operative days. The wound healing resistance was higher in Group 1Y than in Group 2Y after 7 days (P < 0.05). Wound healing resistance at 21 days was higher than at 7 days in all groups (P < 0.05). Late wound healing resistance was not different between young and adult rats. It is concluded that bilateral orchiectomy diminished the wound healing resistance only in young animals at the 7th post-operative day. [source] Pharmacokinetics and tissue distribution of uraemic indoxyl sulphate in ratsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 8 2003Tsuneo Deguchi Abstract The purpose of the present study was to examine the pharmacokinetic properties of indoxyl sulphate, a harmful uraemic toxin that accumulates during chronic renal failure. The pharmacokinetics and tissue distribution of indoxyl sulphate were examined in normal and 5/6 nephrectomized (CRF) rats. The uptake process of indoxyl sulphate by rat renal cortical slices in vitro was also investigated. Endogenous indoxyl sulphate was found to be mainly distributed in the kidney. The rate of elimination of indoxyl sulphate from plasma was lower in CRF rats compared with sham-operated rats. The majority of intact indoxyl sulphate was excreted in the urine. In renal cortical slice experiments, uptake of indoxyl sulphate was a saturable process with a Km of 43.0 ,m. Furthermore, sulphate conjugates, such as oestrone sulphate and dehydroepiandrosterone sulphate, inhibited the uptake of indoxyl sulphate to a greater extent than PAH. Thus, indoxyl sulphate is primarily eliminated from the plasma via the kidney by active tubular secretion, and renal uptake of indoxyl sulphate appears to be mediated by an organic anion transport system with a high affinity for oestrone sulphate and dehydroepiandrosterone sulphate. Copyright © 2003 John Wiley & Sons, Ltd. [source] EPIGALLOCATECHIN-3-GALLATE ATTENUATES CARDIAC HYPERTROPHY IN HYPERTENSIVE RATS IN PART BY MODULATION OF MITOGEN-ACTIVATED PROTEIN KINASE SIGNALSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2009Dan-Dan Chen SUMMARY 1It has been demonstrated that epigallocatechin-3-gallate (EGCG) inhibits cardiac hypertrophy through its antihypertensive and anti-oxidant effects. However, the underlying molecular mechanism is not clear. 2In the present study, we tested the hypothesis that EGCG attenuates transaortic abdominal aortic constriction (TAC)-induced ventricular hypertrophy by regulating mitogen-activated protein kinase (MAPK) signal pathways in hypertensive rats. Four groups of rats were used: (i) a sham-operated control group; (ii) an EGCG-treated (50 mg/kg per day, i.p., for 21 days) sham-operated group; (iii) a TAC group; and (iv) an EGCG-treated TAC group. Histological analysis of whole hearts and biochemical analyses of left ventricular (LV) tissue were used to investigate the effects of EGCG. 3The results showed that the LV myocyte diameter and the expression of atrial natriuretic peptide, brain natriuretic peptide and ,-myocardial heavy chain were significantly decreased in the EGCG-treated (50 mg/kg per day, i.p.) TAC group. Levels of reactive oxygen species and malondialdehyde in the lV were significantly reduced by EGCG in the TAC group. Total superoxide dismutase, catalase and glutathione peroxidase activities were decreased in the TAC group, and this decrease was significantly restored by EGCG treatment. Phosphorylation of extracellular signal-regulated kinase 2, p38 and c-Jun N-terminal kinase 1 was significantly reversed in the LV of EGCG-treated TAC rats (40%, 53% and 52%vs TAC, respectively), accompanied by significant inhibition of nuclear factor-,B and activator protein-1. Transaortic abdominal aortic constriction significantly upregulated LV expression of matrix metalloproteinase-9 from 32 ± 6 to 100 ± 12% and this increase was inhibited by EGCG treatment (from 100 ± 12 to 50 ± 15%). In addition, TAC decreased mitochondrial DNA copy number and the activity of respiratory chain complexes I (from 100 ± 7 to 68 ± 5%), III (from 100 ± 4 to 2 ± 5%) and IV (from 766 ± 2 to 100 ± 5%); this decrease was reversed by EGCG treatment to levels seen in sham-operated rats. 4In conclusion, EGCG attenuates TAC-induced ventricular hypertrophy in hypertensive rats in part by suppression of anti-oxidant enzymes and regulation of MAPK signals. [source] INVOLVEMENT OF PROLYLCARBOXYPEPTIDASE IN THE EFFECT OF RUTAECARPINE ON THE REGRESSION OF MESENTERIC ARTERY HYPERTROPHY IN RENOVASCULAR HYPERTENSIVE RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2009Xu-Ping Qin SUMMARY 1Previous studies indicate that rutaecarpine blocks increases in blood pressure and inhibits vascular hypertrophy in experimentally hypertensive rats. The aim of the present study was to determine whether the effects of rutaecarpine are related to activation of prolylcarboxypeptidase (PRCP). 2Renovascular hypertensive rats (Goldblatt two-kidney, one-clip (2K1C)) were developed using male Sprague-Dawley rats. Chronic treatment with rutaecarpine (10 or 40 mg/kg per day) or losartan (20 mg/kg per day) for 4 weeks to the hypertensive rats caused a sustained dose-dependent attenuation of increases in blood pressure, increased lumen diameter and decreased media thickness, which was accompanied by a similar reduction in the media cross-sectional area : lumen area ratio in mesenteric arteries compared with untreated hypertensive rats. 3Angiotensin (Ang) II expression was significantly increased in mesenteric arteries of hypertensive rats compared with sham-operated rats. No significant differences in plasma AngII levels were observed between untreated hypertensive and sham-operated rats. Hypertensive rats treated with high-dose rutaecarpine had significantly decreased Ang II levels in both the plasma and mesenteric arteries. 4Expression of PRCP protein or kallikrein mRNA was significantly inhibited in the right kidneys and mesenteric arteries of hypertensive rats. However, expression of PRCP protein and kallikrein mRNA was significantly increased after treatment with rutaecarpine or losartan (20 mg/kg per day). 5The data suggest that the repression of increases in systolic blood pressure and reversal of mesenteric artery remodelling by rutaecarpine may be related to increased expression of PRCP in the circulation and small arteries in 2K1C hypertensive rats. [source] | |||||||||||||