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Biomedical subjects

Osamu Yamaguchi

Publications and source records attributed to Osamu Yamaguchi.

At least 37 records · Page 2Linked to original sources
PubMed2004

Cardiac-specific overexpression of sarcolipin inhibits sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2a) activity and impairs cardiac function in mice.

Sarcolipin (SLN) inhibits the cardiac sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA2a) by direct binding and is superinhibitory if it binds through phospholamban (PLN). To determine whether overexpression of SLN in the heart might impair cardiac function, transgenic (TG) mice were generated with cardiac-specific overexpression of NF-SLN (SLN tagged at its N terminus with the FLAG epitope). The level of NF-SLN expression (the NF-SLN/PLN expression ratio) was equivalent to that which induces profound superinhibition when coexpressed with PLN and SERCA2a in HEK-293 cells. In TG hearts, the apparent affinity of SERCA2a for Ca(2+) was decreased compared with non-TG littermate control hearts. Invasive hemodynamic and echocardiographic analyses revealed impaired cardiac contractility and ventricular hypertrophy in TG mice. Basal PLN phosphorylation was reduced. In isolated papillary muscle subjected to isometric tension, peak amplitudes of Ca(2+) transients and peak tensions were reduced, whereas decay times of Ca(2+) transients and relaxation times of tension were increased in TG mice. Isoproterenol largely restored contractility in papillary muscle and stimulated PLN phosphorylation to wild-type levels in intact hearts. No compensatory changes in expression of SERCA2a, PLN, ryanodine receptor, and calsequestrin were observed in TG hearts. Coimmunoprecipitation indicated that overexpressed NF-SLN was bound to both SERCA2a and PLN, forming a ternary complex. These data suggest that NF-SLN overexpression inhibits SERCA2a through stabilization of SERCA2a-PLN interaction in the absence of PLN phosphorylation and through the inhibition of PLN phosphorylation. Inhibition of SERCA2a impairs contractility and calcium cycling, but responsiveness to beta-adrenergic agonists may prevent progression to heart failure.

Animals↗
PubMed2004

Functional and anatomical effects of hormonally induced experimental prostate growth: a urodynamic model of benign prostatic hyperplasia (BPH) in the beagle.

BACKGROUND: Benign prostatic hypertrophy (BPH) produces a variety of changes in the urodynamic pattern of micturition and is usually associated with high detrusor voiding pressure and poor urine flow-rate. In most previous experimental models, designed to simulate this condition, some degree of obstruction is immediately imposed by the technique employed to produce urethral occlusion. Consequently these models cannot reproduce the gradual onset of obstruction. In the present study a canine prostatic enlargement model, using 5alpha-dihydrotestosterone (DHT) + 17beta-estradiol (E) was adapted in order to produce a more gradual onset of partial obstruction and impaired voiding. MATERIALS AND METHODS: Hormonally induced prostatic enlargement was produced using seven beagles, given DHT 75 mg/day together with E 0.75 mg/day for 28 days via an implantable pump. The functional effects of DHT + E treatment on micturition pressure/flow were measured in the conscious animal. Identical measurements were also made using a separate older group of five beagles with symptoms of BPH. In addition seven beagles similarly instrumented were used as controls. RESULTS: Pressure/flow studies show that DHT + E produced obstructive micturition, characterized by a significantly increased micturition detrusor pressure, from 33.3 +/- 10.5 to 50.8 +/- 10.7 cmH(2)O and significantly decreased low urine flow-rate from 8.6 +/- 2.1 to 6.9 +/- 0.9 ml/sec. Associated with the obstructive micturition, this treatment increased wet prostate weight from 11.9 +/- 2.5 to 31.6 +/- 10.0 g. Prostate volume of the BPH beagles was 29.3 +/- 8.9 g. Morphologic studies show that DHT + E produced epithelial hyperplasia extending focally into the lumen. CONCLUSIONS: Hormonally induced prostate growth produced bladder obstruction, in terms of pressure/flow characteristics, that are analogous to BPH. It is suggested that this type of hormonal treatment can be used to create a model for the study of the effects of controlled increased in prostate growth and the development of BPH on micturition.

Age Factors↗
PubMed2004

Response of bladder smooth muscle cells to obstruction: signal transduction and the role of mechanosensors.

Bladder hypertrophy and detrusor overactivity are well-known bladder responses to outlet obstruction. Mechanical stretch stress is considered the trigger inducing these responses in the urodynamically overloaded bladder. Several studies using an in vitro model of mechanical stress demonstrate that repetitive stretch stimulation of bladder smooth muscle cells results in increased expression of a variety of growth factors and other specific proteins. In the bladder smooth muscle cell, stretch-activated ion channels (SACs) and protein kinase C (PKC) sarcolemmal proteins may function as sensors for external mechanical forces. In particular, SACs couple mechanical stress to activation of c-jun NH2-terminal kinase, which leads to a rapid induction of nuclear transcription factors. PKC also may involve an indirect or direct regulation of nuclear events. In addition, mechanical stress may induce the release of angiotensin II in an autocrine fashion. These factors in turn stimulate expression of specific gene-encoding proteins, such as heparin-binding epidermal growth factor-like growth factor, nerve growth factor, and an isomer of cyclooxygenase-2, all of which have the potential to contribute to structural and functional alterations in the bladder after obstruction.

Animals↗
PubMed2004

Ca(2+)-sensitive tyrosine kinase Pyk2/CAK beta-dependent signaling is essential for G-protein-coupled receptor agonist-induced hypertrophy.

G-protein-coupled receptor agonists including endothelin-1 (ET-1) and phenylephrine (PE) induce hypertrophy in neonatal ventricular cardiomyocytes. Others and we previously reported that Rac1 signaling pathway plays an important role in this agonist-induced cardiomyocyte hypertrophy. In this study reported here, we found that a Ca(2+)-sensitive non-receptor tyrosine kinase, proline-rich tyrosine kinase 2 (Pyk2)/cell adhesion kinase beta (CAKbeta), is involved in ET-1- and PE-induced cardiomyocyte hypertrophy medicated through Rac1 activation. ET-1, PE or the Ca(2+) inophore, ionomycin, stimulated a rapid increase in tyrosine phosphorylation of Pyk2. The tyrosine phosphorylation of Pyk2 was suppressed by the Ca(2+) chelator, BAPTA. ET-1- or PE-induced increases in [(3)H]-leucine incorporation and expression of atrial natriuretic factor and the enhancement of sarcomere organization. Infection of cardiomyocytes with an adenovirus expressing a mutant Pyk2 which lacked its kinase domain or its ability to bind to c-Src, eliminated ET-1- and PE-induced hypertrophic responses. Inhibition of Pyk2 activation also suppressed Rac1 activation and reactive oxygen species (ROS) production. These findings suggest that the signal transduction pathway leading to hypertrophy involves Ca(2+)-induced Pyk2 activation followed by Rac1-dependent ROS production.

Animals↗
PubMed2004

Roles of CmpR, a LysR family transcriptional regulator, in acclimation of the cyanobacterium Synechococcus sp. strain PCC 7942 to low-CO(2) and high-light conditions.

The cmp operon of Synechococcus sp. strain PCC 7942, encoding a high-affinity bicarbonate transporter, is induced under low CO(2) conditions by a LysR family protein CmpR. CmpR was found to be required also for induction of the operon by transfer of the cells from low-light to high-light conditions, indicating involvement of a common mechanism in the high-light- and low-CO(2)-responsive regulation. Expression of the high-light inducible genes psbAII and psbAIII, on the other hand, was found to be induced also by low-CO(2) conditions. A single promoter was responsible for the high-light and low-CO(2) induction of each of psbAII and psbAIII, suggesting involvement of a common regulatory mechanism in the light and CO(2) responses of the psbA genes. CmpR was, however, not required for the induction of psbAII and psbAIII, indicating the presence of multiple mechanisms for induction of genes under high-light and low-CO(2) conditions. The CmpR-deficient mutant nevertheless showed lower levels of the psbAII and psbAIII transcripts than the wild-type strain under all the light and CO(2) conditions examined. Gel shift assays showed that CmpR binds to the enhancer elements of psbAII and psbAIII, through specific interaction with a sequence signature conforming to the binding motif of similar LysR family proteins. These findings showed that CmpR acts as a trans-acting factor that enhances transcription of the photosystem II genes involved in acclimation to high light, revealing a complex network of gene regulation in the cyanobacterium.

Bacterial Proteins↗
PubMed2004

p38alpha mitogen-activated protein kinase plays a critical role in cardiomyocyte survival but not in cardiac hypertrophic growth in response to pressure overload.

The molecular mechanism for the transition from cardiac hypertrophy, an adaptive response to biomechanical stress, to heart failure is poorly understood. The mitogen-activated protein kinase p38alpha is a key component of stress response pathways in various types of cells. In this study, we attempted to explore the in vivo physiological functions of p38alpha in hearts. First, we generated mice with floxed p38alpha alleles and crossbred them with mice expressing the Cre recombinase under the control of the alpha-myosin heavy-chain promoter to obtain cardiac-specific p38alpha knockout mice. These cardiac-specific p38alpha knockout mice were born normally, developed to adulthood, were fertile, exhibited a normal life span, and displayed normal global cardiac structure and function. In response to pressure overload to the left ventricle, they developed significant levels of cardiac hypertrophy, as seen in controls, but also developed cardiac dysfunction and heart dilatation. This abnormal response to pressure overload was accompanied by massive cardiac fibrosis and the appearance of apoptotic cardiomyocytes. These results demonstrate that p38alpha plays a critical role in the cardiomyocyte survival pathway in response to pressure overload, while cardiac hypertrophic growth is unaffected despite its dramatic down-regulation.

Animals↗
PubMed2004

Cardiac-specific disruption of the c-raf-1 gene induces cardiac dysfunction and apoptosis.

The Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathway regulates diverse cellular processes such as proliferation, differentiation, and apoptosis and is implicated as an important contributor to the pathogenesis of cardiac hypertrophy and heart failure. To examine the in vivo role of Raf-1 in the heart, we generated cardiac muscle-specific Raf-1-knockout (Raf CKO) mice with Cre-loxP-mediated recombination. The mice demonstrated left ventricular systolic dysfunction and heart dilatation without cardiac hypertrophy or lethality. The Raf CKO mice showed a significant increase in the number of apoptotic cardiomyocytes. The expression level and activation of MEK1/2 or ERK showed no difference, but the kinase activity of apoptosis signal-regulating kinase 1 (ASK1), JNK, or p38 increased significantly compared with that in controls. The ablation of ASK1 rescued heart dysfunction and dilatation as well as cardiac fibrosis. These results indicate that Raf-1 promotes cardiomyocyte survival through a MEK/ERK-independent mechanism.

Animals↗
PubMed2004

[Analysis by computer simulation of double breathing during pressure support ventilation].

BACKGROUND: Pressure support ventilation (PSV) usually provides good patient-ventilator synchrony, but asynchrony is sometimes encountered. Double breathing is one form of asynchrony in which the ventilator assists two or more times during a single inspiration of the patient. METHODS: Double breathing was analyzed using a computer simulation. RESULTS: In an obstructive lung model, inspiratory support was terminated just after the beginning of the inspiration lasting until inspiratory effort triggering the ventilator again. One of the causes of this premature termination was that the compressed and consumed volume in the circuit created a high peak inspiratory flow setting. The other cause was oscillation of the airway pressure. Reducing the circuit volume, slowing the inspiratory rise time, or decreasing the termination criteria could prevent this phenomenon. In a restrictive lung model, the time-constant of the lung was so short that the inspiratory flow finished early and double breathing occurred. It was difficult to prevent this phenomenon by adjusting the circuit assembly or respiratory parameters. CONCLUSIONS: Double breathing during PSV was considered to be closely associated with obstructive or restrictive lung. If the problem arises and cannot be resolved by adjusting ventilatory parameters, the ventilatory mode must be changed.

Airway Resistance↗
PubMed2003

Targeted deletion of apoptosis signal-regulating kinase 1 attenuates left ventricular remodeling.

Left ventricular remodeling that occurs after myocardial infarction (MI) and pressure overload is generally accepted as a determinant of the clinical course of heart failure. The molecular mechanism of this process, however, remains to be elucidated. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in stress-induced apoptosis. We used ASK1 knockout mice (ASK-/-) to test the hypothesis that ASK1 is involved in development of left ventricular remodeling. ASK-/- hearts showed no morphological or histological defects. Echocardiography and cardiac catheterization revealed normal global structure and function. Left ventricular structural and functional remodeling were determined 4 weeks after coronary artery ligation or thoracic transverse aortic constriction (TAC). ASK-/- had significantly smaller increases in left ventricular end-diastolic and end-systolic ventricular dimensions and smaller decreases in fractional shortening in both experimental models compared with WT mice. The number of terminal deoxynucleotidyl transferase biotin-dUDP nick end-labeling-positive myocytes after MI or TAC was decreased in ASK-/- compared with that in WT mice. Overexpression of a constitutively active mutant of ASK1 induced apoptosis in isolated rat neonatal cardiomyocytes, whereas neonatal ASK-/- cardiomyocytes were resistant to H2O2-induced apoptosis. An in vitro kinase assay showed increased ASK1 activity in heart after MI or TAC in WT mice. Thus, ASK1 plays an important role in regulating left ventricular remodeling by promoting apoptosis.

Animals↗
PubMed2003

The small GTP-binding protein Rac1 induces cardiac myocyte hypertrophy through the activation of apoptosis signal-regulating kinase 1 and nuclear factor-kappa B.

The small guanine nucleotide-binding protein Rac1 has emerged as an important molecule involved in cardiac myocyte hypertrophy. Recently, we reported on apoptosis signal-regulating kinase (ASK) 1 and a transcriptional factor, nuclear factor-kappaB (NF-kappaB), as novel signaling intermediates in cardiac myocyte hypertrophy. The aim of the study presented here was to clarify the role of Rac1 in the ASK1-NF-kappaB signaling pathway. Infection of isolated neonatal cardiac myocytes with an adenovirus expressing a constitutively active form of Rac1 (RacV12) enhanced the expression of a kappaB-dependent reporter gene construct and induced the degradation of IkappaBalpha. Expression of a degradation-resistant mutant of IkappaBalpha inhibited the RacV12-induced hypertrophic responses, including increases in protein synthesis and atrial natriuretic factor production and the enhancement of sarcomeric organization. An immune complex kinase assay indicated that the expression of RacV12 activated ASK1. Expression of a dominant negative mutant of ASK1 eliminated the RacV12-induced NF-kappaB activation and the biochemical and morphological hypertrophic responses, whereas expression of a dominant negative form of Rac1 attenuated phenylephrine-induced activation of ASK1 and NF-kappaB and cardiac myocyte hypertrophy. These findings suggest that Rac1 induces cardiac myocyte hypertrophy mediated through ASK1 and NF-kappaB.

Acetylcysteine↗
PubMed2003

Disruption of a single copy of the p38alpha MAP kinase gene leads to cardioprotection against ischemia-reperfusion.

The p38 mitogen-activated protein kinase (p38) is activated in the heart during ischemia-reperfusion. However, it is not clear whether the activation of p38 is the protective response or the kinase mediates the cellular damage by ischemia-reperfusion. We examined the role of p38alpha in ischemia-reperfusion injury by studying p38alpha(+/-) mice. The p38alpha protein level in the p38alpha(+/-) heart was 50+/-8.7% compared with that in the p38alpha(+/+) heart. Upon reperfusion following ischemia for 25min, p38alpha activity was transiently increased. The maximum level of p38 activity in p38alpha(+/-) was 60+/-10.5% compared with that in p38alpha(+/+). In the p38alpha(+/+) heart, 25min ischemia and 2h reperfusion resulted in necrotic injury (37.1+/-2.7% of the area at risk), whereas infarct size was drastically reduced to 7.2+/-0.7% in the p38alpha(+/-) heart. These suggested that p38alpha plays a pivotal role in the signal transduction pathway mediating myocardial cell death caused by ischemia-reperfusion.

Animals↗
PubMed2003

Effect of Pygeum africanum tadenan on micturition and prostate growth of the rat secondary to coadministered treatment and post-treatment with dihydrotestosterone.

OBJECTIVES: Pretreatment with oral tadenan (TAD) has been shown to possess a protective effect on bladder dysfunction-induced obstruction. We evaluated the functional influence of cotreatment and post-treatment with oral TAD on the frequency/volume characteristics of micturition of conscious rats stimulated with exogenous dihydrotestosterone (DHT) to induce experimental prostate growth. METHODS: Studies were done on 36 adult Sprague-Dawley male rats, treated daily for 6 weeks and grouped as follows: group 1, sesame oil during weeks 1 and 2, peanut oil during weeks 3 to 6; group 2, DHT (1.25 mg/kg subcutaneously) dissolved in sesame oil as vehicle during weeks 1 and 2 and peanut oil during weeks 3 to 6; group 3, DHT (1.25 mg/kg subcutaneously) dissolved in sesame oil as vehicle and TAD (100 mg/kg orally) in peanut oil during weeks 1 and 2 and TAD during weeks 3 to 6; and group 4, DHT in sesame oil during weeks 1 and 2 and TAD in peanut oil during weeks 3 to 6. The characteristics of frequency/volume were monitored biweekly and at the sixth week. RESULTS: Controls showed no significant changes from baseline values in volume or frequency during the entire study period. DHT treatment produced a significant increase in frequency (1.9 +/- 0.3 to 3.0 +/- 0.4/hr) and a significant decrease in volume (1.8 +/- 0.3 to 1.2 +/- 0.1 mL). In groups 3 and 4, no significant changes occurred in frequency or volume. By the sixth week of observation, the effects of DHT treatment decreased to control values in all groups. A significant increase in prostatic weight (1191 +/- 11 to 1434 +/- 17 mg/kg) was produced by DHT treatment and TAD cotreatment suppressed growth to 1390 +/- 8.4 mg/kg. CONCLUSIONS: TAD cotreatment or post-treatment suppressed the effects of DHT on micturition, and TAD cotreatment regressed a developing increase in prostatic weight. Post-treatment TAD administration did not reduce already established growth.

Animals↗
PubMed2003

A quantitative analysis of mRNA expression of alpha 1 and beta-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders.

PURPOSE: We compared the expression level of alpha 1-adrenoceptor (AR) subtype mRNA to that of beta-AR subtype mRNA in control and obstructed human bladders, and examined whether alpha 1-AR mediated contraction and beta-AR mediated relaxation of human detrusor muscle are altered by bladder outlet obstruction. MATERIALS AND METHODS: A real-time quantitative reverse transcriptase-polymerase chain reaction based method was used to quantify alpha1 and beta-AR subtype mRNA expression. The contractile response to alpha-AR agonists and the relaxant effect of beta-AR agonists were examined using an isometric contraction technique. RESULTS: The mRNA of alpha 1a, alpha 1b, alpha 1d, beta 1 and beta 2-AR mRNAs was expressed at low levels, while beta 3-AR was the most highly expressed subtype at the mRNA level in control and obstructed bladders. The expression level of alpha 1 and beta-AR subtype mRNA was not significantly different between the 2 groups. The mean contractile response to 10(-4) M phenylephrine +/- SEM was only 4.4% +/- 1.4% and 5.2% +/- 1.4% of the 10(-7) M carbachol induced contraction in the control and obstructed groups, respectively. Contractile responses to phenylephrine were not significantly increased in obstructed bladder. Isoproterenol and the beta 3-AR selective agonist L755,507 relaxed human detrusor muscle in a concentration dependent manner (10(-9) to 10(-4) M). However, the beta 1/beta 2-AR agonist dobutamine and the beta 2-AR selective agonist clenbuterol did not produce relaxation at a concentration of 10(-9) to 10(-5) M in the 2 groups. CONCLUSIONS: These findings indicate that neither up-regulation of alpha1-ARs nor down-regulation of beta-ARs occurs and relaxation mediating beta 3-ARs are by far predominant in the human obstructed bladder. Therefore, it is not likely that bladder alpha1-ARs are responsible for detrusor overactivity and storage symptoms in patients with benign prostatic obstruction.

Adrenergic Agonists↗
PubMed2003

[Pathophysiology of the overactive bladder and its pharmacological treatment].

This paper reviews the possible mechanisms underlying bladder overactivity and discusses the targets for pharmacological treatment of this disorder. Damage to the brain (cerebrovascular disease, etc.) induces bladder overactivity by reducing suprapontine inhibition. Currently, attention has focused on C-fiber bladder afferents that may concern the mechanisms for bladder overactivity resulting from various etiologies such as spinal cord lesions, bladder outlet obstruction and bladder hypersensitivity disorders. With regard to the pathophysiology of idiopathic overactive bladder, both myogenic and neurogenic mechanisms may be involved in involuntary detrusor contraction. Since an intravesical capsaicin or resiniferatoxin was shown to have favorable therapeutic effects, afferent C-fiber neurons become a new target for pharmacological treatment. C-fiber neurons are known to contain tachykinins and other peptides as neurotransmitters. When released, tachykinins can influence via NK receptors bladder activity. In addition, evidences suggest that ATP receptors (P2X3) and prostaglandin receptors in afferent C-fiber neurons may play a role in mediating bladder overactivity. Thus, NK-antagonist, P2X3-antagonist and PG receptor-antagonist may be potential therapeutic drugs in the near future. beta 3-Adrenoceptor agonist is an another candidate drug for the treatment of the overactive bladder. Finally, it is important to notice that in any etiology including an idiopathic one, antimuscarinic drugs can improve bladder overactivity, although dry mouth and constipation are inevitable side-effects.

Humans↗
PubMed2003

[A case of bilateral neonatal testicular torsion].

We report a case of bilateral synchronous testicular torsion in a newborn. A male neonate was referred one day after birth because his left testis was firm and enlarged. We found that the scrotum was firm bilaterally and suspected it to be bilateral testicular tumor. Surgical exploration which was performed at 2 days after birth revealed testicular torsion on both sides. Left orchiectomy, right detorsion biopsy and orchiopexy were performed. Histopathological examination confirmed hemorrhagic necrosis of bilateral testes.

Diagnosis, Differential↗
PubMed2002

Cardiac-specific overexpression of a high Ca2+ affinity mutant of SERCA2a attenuates in vivo pressure overload cardiac hypertrophy.

In cardiomyocytes, calcium plays important roles as a signal in cardiac hypertrophy and contraction-relaxation cycling. Elevation of Ca2+ concentration in myoplasm is associated with the onset and progression of hypertrophy as well as the enhancement of contractility. The cardiac Ca2+ ATPase (SERCA2a) of the sarcoplasmic reticulum plays a dominant role in lowering cytoplasmic calcium levels during relaxation and is regulated by phospholamban (PLN). To examine whether the modulation of SERCA2a activity results in the attenuation of cardiac hypertrophy and enhancement of contractility, we generated transgenic mice (TG) overexpressing a high calcium affinity SERCA2a mutant (K397/400E), lacking a functional association with PLN. In the TG hearts, the apparent affinity of SERCA2a for Ca2+ significantly increased compared with their nontransgenic littermate controls. The TG showed increased contraction and relaxation, with increases in the amplitude of Ca2+ transient and rapid Ca2+ decay. Upon induction of pressure overload by transverse aortic constriction, the TG developed less cardiac hypertrophy than littermate controls did. The activation of Ca2+-sensitive protein kinase C by pressure overload was significantly attenuated in the TG hearts. Our findings indicate an association of SERCA2a activity with cardiac hypertrophy and thus a new therapeutic target for the prevention and treatment of cardiac hypertrophy.

Animals↗
PubMed2002

The antioxidant N-2-mercaptopropionyl glycine attenuates left ventricular hypertrophy in in vivo murine pressure-overload model.

OBJECTIVES: In order to identify the role of reactive oxygen species (ROS) in cardiac hypertrophy, we examined the effect of N-2-mercaptopropionyl glycine (MPG) on cardiac hypertrophy. BACKGROUND: Recent in vitro studies have suggested that ROS play an important role as a second messenger in cardiac hypertrophy. It was therefore thought to be of particular value to examine the relevance of studies using in vitro models for cardiac hypertrophy in an in vivo setting. METHODS: The transverse thoracic aorta in mice was constricted, and MPG (100 mg/kg) was infused intraperitoneally twice daily. The animals were assessed seven days after the operation for hemodynamic functions, oxidative stress and antioxidative enzyme activities. RESULTS: Banding of the transverse aorta in mice resulted in an increase in the ratio of heart weight to tibia length and the appearance of an endogenous atrial natriuretic factor messenger ribonucleic acid (mRNA) seven days postoperatively. Administration of MPG significantly attenuated the hypertrophic responses induced by pressure overload. Cardiac hypertrophy was accompanied by increases in heme oxygenase-1 mRNA expression and lipid peroxidation, which was eliminated by the treatment with MPG. Pressure overload led to increases in antioxidant enzyme activities, such as superoxide dismutase and glutathione peroxidase, but not catalase, activity. CONCLUSIONS: Our results indicated that oxidative stress was increased in our model and that it plays an important role in the development of cardiac hypertrophy.

Animals↗