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Naoyuki Hasebe

Publications and source records attributed to Naoyuki Hasebe.

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

Thermal treatment attenuates neointimal thickening with enhanced expression of heat-shock protein 72 and suppression of oxidative stress.

BACKGROUND: The beneficial effects of thermal therapy have been reported in several cardiovascular diseases. However, it is unknown whether the thermal treatment has some beneficial roles against the development of atherosclerosis. METHODS AND RESULTS: The inflammatory arterial lesion was introduced by placement of a polyethylene cuff on femoral arteries of male Sprague-Dawley rats for 4 weeks. Thermal-treated group underwent daily bathing in 41 degrees C hot water for 15 minutes. Neointimal thickening along with immunohistochemical expression of heat-shock proteins (HSPs), monocyte chemoattractant protein-1 (MCP-1), and NADPH oxidase were compared with those of a thermally untreated (Control) group. Morphometric analysis demonstrated a significant suppression of neointimal thickening in thermal-treated group compared with the Control group (intimal/medial area ratios, 0.01+/-0.01 versus 0.31+/-0.04, P<0.01). Expression of MCP-1 and infiltration of ED-positive cells were enhanced in the adventitial layer of Control. More importantly, expression of HSP72 in media was enhanced by thermal treatment. Expression of p22-phox, the major membrane subunit of NADPH oxidase, and MCP-1 was augmented in cuff-injured adventitia of the Control but not the thermal-treated groups. CONCLUSIONS: Thermal treatment significantly attenuated infiltration of inflammatory cells in adventitia and suppressed neointimal thickening in cuff-injured arteries with the enhancement of HSP72 expression and suppression of oxidative stress.

Animals↗
PubMed2004

Decreased susceptibility to renovascular hypertension in mice lacking the prostaglandin I2 receptor IP.

Persistent reduction of renal perfusion pressure induces renovascular hypertension by activating the renin-angiotensin-aldosterone system; however, the sensing mechanism remains elusive. Here we investigated the role of PGI2 in renovascular hypertension in vivo, employing mice lacking the PGI2 receptor (IP-/- mice). In WT mice with a two-kidney, one-clip model of renovascular hypertension, the BP was significantly elevated. The increase in BP in IP-/- mice, however, was significantly lower than that in WT mice. Similarly, the increases in plasma renin activity, renal renin mRNA, and plasma aldosterone in response to renal artery stenosis were all significantly lower in IP-/- mice than in WT mice. All these parameters were measured in mice lacking the four PGE2 receptor subtypes individually, and we found that these mice had similar responses to WT mice. PGI2 is produced by COX-2 and a selective inhibitor of this enzyme, SC-58125, also significantly reduced the increases in plasma renin activity and renin mRNA expression in WT mice with renal artery stenosis, but these effects were absent in IP-/- mice. When the renin-angiotensin-aldosterone system was activated by salt depletion, SC-58125 blunted the response in WT mice but not in IP-/- mice. These results indicate that PGI2 derived from COX-2 plays a critical role in regulating the release of renin and consequently renovascular hypertension in vivo.

Animals↗
PubMed2004

[Heart failure].

Explore the source record for details and available documents.

Arteriosclerosis↗
PubMed2004

[Effects of calcium channel blockers in atherosclerosis and cardiovascular event and oxidative vascular damage].

Ca antagonists are relevant therapeutic tool for patients with hypertension. The effects of Ca antagonists against oxidative vascular damage and followed atherosclerosis were elucidated in various experimental model accompanied with the vasodilatative effects of Ca antagonists by blocking the L-type Ca channel. The beneficial effects of Ca antagonists in cardiovascular disease have been demonstrated in several clinical trials, as we demonstrated the beneficial effect of Ca antagonist in the incidence of cardiovascular event in Japanese patients with coronary disease. In patient with diabetes mellitus, the cardiovascular disease was also caused by the mechanism involved with the increase in oxidative stress in blood vessels and related factors such as advanced glycation endproducts, protein kinase C and insulin resistance. The beneficial effects of Ca antagonists in cardiovascular disease in patients with diabetes mellitus have been demonstrated in several clinical trials, may be dependent on the effect of Ca antagonist against the oxidative stress in the setting of hyperglycemia.

Animals↗
PubMed2003

Inhaled nitric oxide modifies left ventricular diastolic stress in the presence of vasoactive agents in heart failure.

Nitric oxide (NO) inhalation therapy has been widely used in several diseases with pulmonary hypertension. However, application of NO inhalation therapy remains controversial in heart failure. Cardiovascular effects of inhaled NO (iNO) were evaluated in dogs before and after induction of heart failure with and without infusion of vasoactive agents. iNO did not affect the baseline left ventricular (LV) function or the response to isoproterenol in control conditions or heart failure induced by procainamide. Pulmonary vascular resistance was significantly decreased by iNO in heart failure with infusion of vasoactive agents. Unexpectedly, LV end-diastolic pressure was significantly elevated by iNO in heart failure in the presence of infusion of vasoactive agents independent of their types; either the vasodilating agents of acetylcholine and nitroglycerin or the vasoconstricting agents of norepinephrine and angiotensin-II. The end-diastolic LV dimension and wall stress were also significantly increased by iNO, however, those at end systole were not affected. These results suggested that NO inhalation therapy reduced pulmonary vascular resistance, whereas in the presence of additional stress of vasoactive agents, it increased LV preload and end-diastolic wall stress in heart failure.

Acetylcholine↗
PubMed2003

Comparison of myocardial fatty acid metabolism with left ventricular function and perfusion in cardiomyopathies: by 123I-BMIPP SPECT and 99mTc-tetrofosmin electrocardiographically gated SPECT.

OBJECTIVE: To investigate myocardial fatty acid metabolism and its relationship with left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). METHODS: Thirty-nine patients with cardiomyopathies (58 +/- 14 y), comprising 15 DCM and 24 HCM, and 9 age-matched healthy controls were studied with 123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and 99mTc-tetrofosmin (TF) electrocardiographically gated SPECT. As parameters of myocardial fatty acid metabolism, the heart-to-mediastinum ratio (H/M) and global washout of BMIPP were calculated from early and delayed planar images, while regional BMIPP uptake and washout were calculated from SPECT. In TF study, the H/M (H/M-TF) and LV ejection fraction (LVEF) were calculated as global parameters of perfusion and function, while regional TF uptake and wall thickening index were calculated as regional parameters of perfusion and function using the Quantitative Gated SPECT software. The differences in the parameters and the correlations between the parameters from the 2 studies were investigated by one-way ANOVA and multiple linear regression analysis. RESULTS: BMIPP uptake was decreased (p < 0.05), and its washout was increased (p < 0.05) in DCM and HCM. In multiple linear regression analysis, global BMIPP parameters showed no significant correlation with LVEF (p > 0.05), but showed a significant correlation with H/M-TF (p < 0.05) in DCM and HCM. According to the partial correlation coefficient, early H/M was the only significant factor (p < 0.05) for predicting H/M-TF in DCM and HCM. Multiple linear regression analysis on regional parameters showed regional BMIPP parameters had no correlation with regional function (p > 0.05) but had a significant correlation with regional perfusion (p < 0.0001) in DCM. In HCM, regional BMIPP parameters showed significant multiple linear correlations with both regional function (p < 0.005) and perfusion (p < 0.0001). According to the partial correlation coefficients, delayed regional BMIPP uptake was the most significant factor for predicting regional function in HCM, while early regional BMIPP uptake was the only or the most significant factor for predicting regional perfusion in DCM and HCM, respectively. CONCLUSION: In DCM, BMIPP uptake and washout could not reflect LV function. In HCM, regional delayed BMIPP uptake might be useful for evaluating regional function. In DCM and HCM, early BMIPP uptake might be largely determined by myocardial perfusion.

Adolescent↗
PubMed2003

Roles of calcineurin and calcium/calmodulin-dependent protein kinase II in pressure overload-induced cardiac hypertrophy.

Calcineurin and calcium/calmodulin-dependent protein kinase (CaMK) II have been suggested to be the signaling molecules in cardiac hypertrophy. It was not known, however, whether these mechanisms are involved in cardiac hypertrophy induced by pressure overload without the influences of blood-derived humoral factors, such as angiotensin II. To elucidate the roles of calcineurin and CaMK II in this situation, we examined the effects of calcineurin and CaMK II inhibitors on pressure overload-induced expression of c-fos, an immediate-early gene, and protein synthesis using heart perfusion model. The hearts isolated from Sprague-Dawley rats were perfused according to the Langendorff technique, and then subjected to the acute pressure overload by raising the perfusion pressure. The activation of calcineurin was evaluated by its complex formation with calmodulin and by its R-II phosphopeptide dephosphorylation. CaMK II activation was evaluated by its autophosphorylation. Expression of c-fos mRNA and rates of protein synthesis were measured by northern blot analysis and by 14C-phenylalanine incorporation, respectively. Acute pressure overload significantly increased calcineurin activity, CaMK II activity, c-fos expression and protein synthesis. Cyclosporin A and FK506, the calcineurin inhibitors, significantly inhibited the increases in both c-fos expression and protein synthesis. KN62, a CaMK II inhibitor, also significantly prevented the increase in protein synthesis, whereas it failed to affect the expression of c-fos. These results suggest that both calcineurin and CaMK II pathways are critical in the pressure overload-induced acceleration of protein synthesis, and that transcription of c-fos gene is regulated by calcineurin pathway but not by CaMK II pathway.

Animals↗
PubMed2003

A case of a short-coupled variant of torsades de Pointes with electrical storm.

This case report describes a short-coupled variant of Torsades de Pointes with a characteristic ECG pattern consisting of a prominent J wave in leads V3-V6, in which an electrical storm was evoked with autonomic receptor stimulation and a blockade test. The patient's frequent VF attacks were triggered by short-coupled premature ventricular contractions with a right bundle branch block morphology and left-axis deviation, and were suppressed by deep sedation followed by a combination therapy using verapamil and mexiletine. Interestingly, with the use of those drugs, the prominent J wave diminished. The mechanism underlying this syndrome is discussed.

Electrocardiography↗
PubMed2003

Effect of beta-adrenoceptor antagonist and angiotensin-converting enzyme inhibitor on hypertension-associated changes in adenylyl cyclase type V messenger RNA expression in spontaneously hypertensive rats.

Adenylyl cyclase (AC) messenger RNA (mRNA) expression is decreased in failing hearts. Diminished expressions are accompanied by desensitization of beta-adrenergic signal transduction. Factors contributing to such changes in mRNA expression for the major myocardial isoform AC V are not well established. To assess the contributions of hypertension, left ventricular hypertrophy (LVH), the renin-angiotensin-aldosterone system (RAS), and the sympathetic nervous system to these changes, ventricular expression of AC V mRNA was measured at different ages in spontaneously hypertensive rats (SHRs). In addition, the effects on them of angiotensin-converting enzyme inhibitor and beta-adrenoceptor antagonists were determined. Prior to quantitative Northern blotting at ages 5, 9, or 12 weeks, hemodynamic and morphologic variables were measured in SHRs and Wistar-Kyoto rats (WKYs). The SHRs and WKYs were treated with an angiotensin-converting enzyme inhibitor, enalapril (10 mg/kg/d), or a beta(1)-adrenoceptor antagonist, atenolol (100 mg/kg/d), for 8 weeks preceding Northern analysis. Myocardial AC V mRNA expression increased from 5-12 weeks in both SHRs and WKYs. Expression of AC V mRNA in SHRs increased somewhat less than in WKYs at 9 weeks and significantly less at 12 weeks. This was accompanied by development of LVH and hypertension in SHRs. Blood pressure and left ventricular weight relative to body weight were markedly decreased by enalapril and were moderately decreased by atenolol. Expression of AC V mRNA in SHRs at 12 weeks was normalized equally by enalapril and atenolol to the level of WKYs. Thus AC V mRNA expression increases are blunted in the early stages of LVH in SHRs under the influences of beta(1)-adrenergic signal transduction and the RAS.

Adenylyl Cyclases↗
PubMed2003

Cervical and intracranial atherosclerosis and silent brain infarction in Japanese patients with coronary artery disease.

PURPOSE: To investigate the prevalence of cervical and intracranial atherosclerosis and silent brain infarction in patients with coronary artery disease (CAD). METHODS: Cervical and intracranial atherosclerotic lesions on magnetic resonance angiography (MRA) and silent brain infarctions on magnetic resonance imaging (MRI) were investigated in comparison with the findings of coronary angiography in 133 consecutive patients with CAD. RESULTS: The mean severity scores of cervical and intracranial MRA lesions were significantly higher in the three-vessel CAD (0.40 and 0.53, respectively) than in the zero-vessel CAD group (0.04 and 0.11). The mean scores of the maximal size and multiplicity of MRI lesion were also significantly greater in the two-vessel (1.00 and 1.44) and three-vessel CAD (0.94 and 1.26) than in the zero-vessel CAD group (0.27 and 0.50). The incidence of MRA lesion was markedly higher in patients with brain MRI lesion than in those without (51.1 vs. 6.5%). CONCLUSIONS: Serious coronary artery lesions were commonly accompanied by latent atherosclerotic lesions in the cervical and intracranial arteries besides silent brain infarction in patients with CAD.

Adult↗
PubMed2003

Recovery of BMIPP uptake and regional wall motion in insulin resistant patients following angioplasty for acute myocardial infarction.

The effect of insulin resistance (IR) on the fatty acid metabolism of myocardium, and therefore on the recovery of left ventricular (LV) wall motion, has not been established in patients with acute myocardial infarction (AMI). A total of consecutive 58 non-diabetic AMI patients who had successfully undergone emergency coronary angioplasty were analyzed retrospectively. They were categorized into 2 groups, normal glucose tolerance (NGT) and impaired glucose tolerance (IGT), based on a 75-g oral glucose tolerance test (OGTT). The parameters of OGTT, myocardial scintigraphy (n=58) (thallium-201 (Tl) and iodine-123-beta-methyl-iodophenylpentadecanoic acid (BMIPP)) and left ventriculography (n=24) were compared in the 2 groups after reperfusion (acute phase) and 3-4 weeks after the AMI (chronic phase). The insulin resistance (IR), estimated by the serum concentration of insulin at 120 min (IRI 120') of the OGTT and by the HOMA (the homeostasis model assessment) index, was higher in the IGT group than in NGT group. An inverse correlation was found between the recovery of regional LV wall motion in the ischemic lesion and the IRI 120' and HOMA index. Although the recovery of BMIPP uptake from the acute to the chronic phase was higher in the IGT group, it was only correlated with the degree of IRI 120', not with the HOMA. IR accompanied by IGT can negatively influence the recovery of regional LV wall motion.

Aged↗
PubMed2003

A case of nephrotic syndrome associated with renovascular hypertension successfully treated with candesartan.

A sixty eight-year-old man was referred to our hospital for evaluation of hypertension and hypokalemia. His chief complaints were fatigability and weakness of the lower extremities. Atrophy of the right kidney was noted on computed tomography. The laboratory findings demonstrated massive proteinuria, markedly elevated plasma renin activity, hypokalemia, and renal insufficiency. Angiography showed total occlusion of the right renal artery. The patient was diagnosed as having nephrotic syndrome associated with renovascular hypertension. Treatment with candesartan, an angiotensin-II-receptor blocker (ARB), controlled both hypertension and proteinuria satisfactorily without worsening of his renal function. This is the first report on the effect of ARB on nephrotic syndrome associated with renovascular hypertension. Based on the results, ARB can be considered a promising agent for the treatment of patients with renovascular hypertension with massive proteinuria and renal insufficiency.

Aged↗
PubMed2003

Effects of temocapril and olmesartan on myocardial sympathetic nervous activity and fatty acid metabolism in rats with chronic beta-adrenergic stimulation.

We investigated the effects of an angiotensin-converting enzyme inhibitor (temocapril) and an angiotensin II type 1 receptor blocker (olmesartan) on changes in myocardial sympathetic nervous activity, fatty acid metabolism and myocardial blood flow using 131I-meta-iodobenzylguanidine, 125I-beta-methyl-iodophenyl pentadecanoic acid and 99mTc-tetrofosmin, respectively, in rats with isoproterenol-induced cardiac hypertrophy. Male Sprague-Dawley rats underwent isoproterenol administration (3 mg/kg per day) for 1 week by osmotic mini-pump. The hearts were excised and analyzed for the uptake of meta-iodobenzylguanidine. Beta-methyl-iodophenyl pentadecanoic acid and tetrofosmin in 11 segments in four groups; sham group (saline), isoproterenol group (isoproterenol alone), angiotensin-converting enzyme inhibitor group (isoproterenol and temocapril), and angiotensin II type 1 receptor blocker group (isoproterenol and olmesartan). Isoproterenol significantly increased the heart weight compared with the sham group, whereas it was significantly blunted in the angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor blocker groups. The ratio of the percent kilogram dose per gram of meta-iodobenzylguanidine to tetrofosmin, an index of myocardial sympathetic nervous activity, was significantly decreased in the isoproterenol group (0.18 +/- 0.01) compared with the sham group (0.41 +/- 0.03). Importantly, these changes were significantly improved in the angiotensin-converting enzyme inhibitor (0.28 +/- 0.01) and the angiotensin II type 1 receptor blocker groups (0.32 +/- 0.01). The ratio of the percent kilogram dose per gram of beta-methyl-iodophenyl pentadecanoic acid to tetrofosmin, an index of myocardial fatty acid metabolism, was significantly decreased in the isoproterenol group (1.30 +/- 0.03) compared with the sham group (1.60 +/- 0.10). In contrast, there were no significant differences in beta-methyl-iodophenyl pentadecanoic acid to tetrofosmin ratios between the sham and angiotensin-converting enzyme inhibitor groups, or the angiotensin II type 1 receptor blocker group. Cardiac hypertrophy induced by chronic beta-adrenergic stimulation is accompanied by impairment of sympathetic nervous activity and fatty acid metabolism. These abnormalities are effectively prevented by the angiotensin-converting enzyme inhibitor and the angiotensin II type 1 receptor blocker.

Adrenergic Fibers↗
PubMed2002

Contribution of macrophage migration inhibitory factor to extracellular signal-regulated kinase activation by oxidative stress in cardiomyocytes.

In response to oxidative stress, the pathogenesis of a number of cardiovascular events and several genes are stimulated by extracellular signal-regulated kinases (ERK1/2). Biphasic (early, 10 min; and delayed, 120 min) ERK1/2 activation by H(2)O(2), a reactive oxygen species, was observed in cultured neonatal rat cardiomyocytes. We investigated the hypothesis that the delayed activation of ERK1/2 depends on a factor secreted by oxidative stress (FSO). The delayed activation was inhibited by calphostin C, a protein kinase C inhibitor. Conditioned medium (CM) obtained from cells stimulated with H(2)O(2) induced rapid and monophasic ERK1/2 activation, which was not inhibited by calphostin C. In contrast, calphostin C-pretreated CM did not activate ERK1/2. Macrophage migration inhibitory factor (MIF) was one of the candidate FSOs activating ERK1/2. The existence of MIF in CM, the recombinant MIF-stimulated ERK1/2 rapid activation, and anti-MIF neutralizing antibody-induced inhibition of the delayed activation implied that MIF could be the FSO. Pretreatment of cardiomyocytes with a mitogen-activated protein kinase/ERK kinase (MEK) inhibitor did not suppress the MIF secretion, although it prevented the ERK1/2 activation by H(2)O(2). These results indicate that MIF is secreted from cardiomyocytes as a result of oxidative stress and activates ERK1/2 through a MEK1/2-dependent mechanism, although the secretion is not regulated by ERK1/2 but by protein kinase C.

Animals↗
PubMed2002

Magnesium reduces myocardial infarct size via enhancement of adenosine mechanism in rabbits.

OBJECTIVES: Clinical impact of magnesium (Mg) therapy remains controversial in acute myocardial infarction. We investigated the infarct size limiting effects of Mg and its mechanism in rabbits. METHODS: Anesthetized rabbits underwent 30 min coronary occlusion and 3 h reperfusion in ten groups: (1) Control, (2) Low Mg, (3) Mg, (4) High Mg, (5) calcium (Ca), (6) Mg+Ca, (7) 8-phenyltheophylline (8PT), an adenosine receptor blockade, (8) 8PT+Mg, (9) alpha, beta-methylene-adenosine diphosphate (AOPCP), a selective inhibitor of ecto-5'-nucleotidase, and (10) AOPCP+Mg groups. Infract size (IS) to area at risk (AR) was measured by triphenyltetrazorium chloride method. RESULTS: The IS/AR ratio was significantly smaller in Mg, 27+/-3% (P<0.05) and High Mg, 24+/-2% (P<0.05) compared to Control, 50+/-3% and Low Mg, 42+/-4%. The IS limiting effects of Mg were abolished in 8PT+Mg, AOPCP+Mg and Mg+Ca. The IS/AR ratio correlated with neither rate-pressure products nor incidence of arrhythmia. CONCLUSION: Magnesium administration has an infarct size limiting effect independent of its effects on myocardial oxygen consumption and incidence of arrhythmia in rabbits. The infarct size limiting effect of magnesium is attributable, at least in part, to augmentation of adenosine mechanism.

5'-Nucleotidase↗
PubMed2002

Effects of the prostanoids on the proliferation or hypertrophy of cultured murine aortic smooth muscle cells.

Effects of the prostanoids on the growth of cultured aortic vascular smooth muscle cells (VSMCs) were examined using mice lacking prostanoid receptors. Proliferation of VSMCs was assessed by measuring [(3)H]-thymidine incorporation and the cell number, and their hypertrophy by [(14)C]-leucine incorporation and protein content. In VSMCs from wild-type mice, expressions of mRNAs for the EP(4) and TP were most abundant, followed by those for the IP, EP(3) and FP, when examined by competitive reverse transcriptase-PCR. Those for the EP(1), EP(2) and DP, however, could not be detected. AE1-329, an EP(4) agonist, and cicaprost, an IP agonist, inhibited platelet derived growth factor (PDGF)-induced proliferation of VSMCs from wild-type mice; these inhibitory effects disappeared completely in VSMCs from EP(4)(-/-) and IP(-/-) mice, respectively. In accordance with these effects, AE1-329 and cicaprost stimulated cAMP production in VSMCs from wild-type mice, which were absent in VSMCs from EP(4)(-/-) and IP(-/-) mice, respectively. Effects of PGE(2) on cell proliferation and adenylate cyclase were almost similar with those of AE1-329 in VSMCs from wild-type mice, which disappeared in VSMCs from EP(4)(-/-) mice. PGD(2) inhibited PDGF-induced proliferation of VSMCs from both wild-type and DP(-/-) mice to a similar extent. This action of PGD(2) was also observed in VSMCs from EP4(-/-) and IP(-/-) mice. In VSMCs from wild-type mice, I-BOP, a TP agonist, showed potentiation of PDGF-induced hypertrophy. I-BOP failed to show this action in VSMCs from TP(-/-) mice. The specific agonists for the EP(1), EP(2) or EP(3), and PGF(2)alpha showed little effect on the growth of VSMCs. These results show that PGE(2), PGI(2) and TXA(2) modulate PDGF-induced proliferation or hypertrophy of VSMCs via the EP(4), IP and TP, respectively, and that the inhibitory effect of PGD(2) on PDGF-induced proliferation is not mediated by the DP, EP(4) or IP.

Animals↗
PubMed2002

Effects of right stellate ganglion block on the autonomic nervous function of the heart: a study using the head-up tilt test.

The effect of peripheral sympathetic block on the autonomic nerve function of the heart was studied using the head-up tilt test (HUTT) and right stellate ganglion block (RSGB). Blood pressure (BP), heart rate (HR) and the parameters of power spectral analysis of HR variability recorded during the HUTT were measured in 8 patients with chronic pain syndrome before and after RSGB. In the control state, the mean HR and the LF/HF component recorded during HUTT significantly increased whereas the HF component markedly decreased. Conversely, the mean HR and LF/HF and HF components during HUTT did not significantly alter after the RSGB procedure. There were no significant differences between the BP values before and after RSGB. These results suggest that RSGB suppresses cardiac sympathetic function without significantly affecting BP and thus may be a safe and effective therapy for the chronic pain syndrome.

Adult↗