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Kazuyuki Shimada

Publications and source records attributed to Kazuyuki Shimada.

At least 19 recordsLinked to original sources
PubMed2003

Comparison of candesartan with lisinopril on ambulatory blood pressure and morning surge in patients with systemic hypertension.

We performed a prospective crossover study in 73 essential hypertensives to compare the effects of candesartan and lisinopril on ambulatory blood pressure (BP) and early-morning BP. Twenty-four-hour ambulatory BP monitoring was performed at baseline and for each active treatment. Small doses of thiazide diuretic were added as needed. The effects of both drugs on 24-hour BP were almost identical and satisfactory. When we classified patients into the morning surge group (the highest quartile of morning systolic BP surge >36 mm Hg) and the non-morning surge group (the remaining 3 quartiles of morning BP surge), candesartan was superior in decreasing morning BP and morning BP surge.

Aged↗
PubMed2003

DNA microarray analysis of in vivo progression mechanism of heart failure.

Dahl salt-sensitive rats are genetically hypersensitive to sodium intake. When fed a high sodium diet, they develop systemic hypertension, followed by cardiac hypertrophy and finally heart failure within a few months. Therefore, Dahl rats represent a good model with which to study how heart failure is developed in vivo. By using DNA microarray, we here monitored the transcriptome of >8000 genes in the left ventricular muscles of Dahl rats during the course of cardiovascular damage. Expression of the atrial natriuretic peptide gene was, for instance, induced in myocytes by sodium overload and further enhanced even at the heart failure stage. Interestingly, expression of the gene for the D-binding protein, an apoptotic-related transcriptional factor, became decreased upon the transition to heart failure. To our best knowledge, this is the first report to describe the transcriptome of cardiac myocytes during the disease progression of heart failure.

Animals↗
PubMed2003

Antiapoptotic effect of endothelin-1 in rat cardiomyocytes in vitro.

Apoptosis of cardiac myocytes is thought to be a feature of many pathological disorders, including congestive heart failure (CHF) and ischemic heart disease (IHD). Because recent investigations indicate that endothelin-1 (ET-1) plays an important role in CHF and IHD, we investigated the effect of ET-1 on cardiomyocyte apoptosis. The presence of apoptosis in rat cardiomyocytes (H9c2 and neonatal) was evaluated by morphological criteria, electrophoresis of DNA fragments, 4',6'-diamidine-2'-phenylindole staining, and TUNEL analysis. ET-1, but not angiotensin II, prevented apoptosis induced by serum deprivation via ETA receptors in a dose-dependent manner (1 to 100 nmol/L). ET-1 also prevented cytochrome c release from mitochondria to the cytosol. The use of specific pharmacological inhibitors demonstrated that the antiapoptotic effect of ET-1 was mediated through a tyrosine kinase pathway (genistein and AG490) but not through protein kinase C (PKC; calphostin C), mitogen-activated protein kinases (PD98059 and SB203580), or PKA (KT5270) pathways. Adenovirus-mediated gene transfer of kinase-inactive (KI) c-Src reversed the antiapoptotic effect of ET-1. We further investigated whether Bcl-xL, an antiapoptotic molecule, would be upregulated by using a luciferase-based reporter system. ET-1 upregulated Bcl-xL, and this upregulation was inhibited by genistein or AG490 but not by calphostin C. The experiments with KI mutants for various tyrosine kinases revealed that c-Src and Pyk2 (but not JAK1, Jak2, Syk, and Tec) are involved in ET-1-induced upregulation of Bcl-xL expression. These findings suggest that ET-1 prevents apoptosis in cardiac myocytes through the ETA receptor and the subsequent c-Src/Bcl-xL-dependent pathway.

Animals↗
PubMed2003

Morning surge in blood pressure as a predictor of silent and clinical cerebrovascular disease in elderly hypertensives: a prospective study.

BACKGROUND: Cardiovascular events occur most frequently in the morning hours. We prospectively studied the association between the morning blood pressure (BP) surge and stroke in elderly hypertensives. METHODS AND RESULTS: We studied stroke prognosis in 519 older hypertensives in whom ambulatory BP monitoring was performed and silent cerebral infarct was assessed by brain MRI and who were followed up prospectively. The morning BP surge (MS) was calculated as follows: mean systolic BP during the 2 hours after awakening minus mean systolic BP during the 1 hour that included the lowest sleep BP. During an average duration of 41 months (range 1 to 68 months), 44 stroke events occurred. When the patients were divided into 2 groups according to MS, those in the top decile (MS group; MS > or =55 mm Hg, n=53) had a higher baseline prevalence of multiple infarcts (57% versus 33%, P=0.001) and a higher stroke incidence (19% versus 7.3%, P=0.004) during the follow-up period than the others (non-MS group; MS <55 mm Hg, n=466). After they were matched for age and 24-hour BP, the relative risk of the MS group versus the non-MS group remained significant (relative risk=2.7, P=0.04). The MS was associated with stroke events independently of 24-hour BP, nocturnal BP dipping status, and baseline prevalence of silent infarct (P=0.008). CONCLUSIONS: In older hypertensives, a higher morning BP surge is associated with stroke risk independently of ambulatory BP, nocturnal BP falls, and silent infarct. Reduction of the MS could thus be a new therapeutic target for preventing target organ damage and subsequent cardiovascular events in hypertensive patients.

Aged↗
PubMed2003

Matrix metalloproteinases and coronary artery diseases.

Matrix metalloproteinases (MMPs) play an important role in cardiovascular remodeling by degrading the extracellular matrix. Enhanced MMP expression has been detected in the atherosclerotic plaque, and activation of MMPs appears to be involved in the vulnerability of the plaque. Circulating MMP levels are elevated in patients with acute myocardial infarction and unstable angina. Increased MMP expression is also observed after coronary angioplasty, which is related to late loss index after the procedure. These observations suggest that MMP expression may be not only related to instability of the plaque, but also to the formation of restenotic lesions. The development of therapeutic drugs targeted specifically against MMPs may be useful in the prevention of atherosclerotic lesion development, plaque rupture, and restenosis.

Coronary Artery Disease↗
PubMed2003

Associations between nondipping of nocturnal blood pressure decrease and cardiovascular target organ damage in strictly selected community-dwelling normotensives.

BACKGROUND: In hypertensives, nondippers are more likely than dippers to suffer silent, as well as overt, hypertensive target organ damage. In this study, we investigated whether a nondipper status was associated with target organ damage in normotensives. METHODS: We performed ambulatory blood pressure (BP) monitoring, echocardiography, and carotid ultrasonography and measured natriuretic peptides and urinary albumin (UAE) in 74 normotensive subjects with the following criteria: 1) clinical BP <140/90 mm Hg; 2) average 24-h ambulatory BP <125/80 mm Hg. RESULTS: The left ventricular mass index (LVMI) and the relative wall thickness (RWT) measured by echocardiography were greater in nondippers than dippers (LVMI: 103 +/- 26 v 118 +/- 34 g/m(2), P <.05; RWT: 0.38 +/- 0.07 v 0.43 +/- 0.09, P <.01). Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were higher in nondippers than dippers (ANP: 14 +/- 10 v 36 +/- 63 pg/mL, P <.01; BNP: 16 +/- 12 v 62 +/- 153 pg/mL, P <.05). There were no significant differences in UAE and intima-media thickness measured by carotid ultrasonography. CONCLUSIONS: Normotensive nondipping may not reflect renal damage, but may have a predominant effect on cardiac damage. Nondipping of nocturnal BP seems to be a determinant of cardiac hypertrophy and remodeling, and may result in a cardiovascular risk independent of ambulatory BP levels in normotensives.

Aged↗
PubMed2003

Intravenous prostaglandin E1 reduces monocyte chemoattractant protein-1 levels in peripheral arterial obstructive disease.

OBJECTIVES: Blood monocytes are the precursors of the lipid-laden foam cells that are the hallmark of early atherosclerotic lesions, and monocyte chemoattractant protein-1 (MCP-1) plays important roles in their recruitment to the vessel wall. In this study, we measured serum levels of MCP-1 in patients with peripheral arterial obstructive disease (PAOD) and investigated whether intravenous prostaglandin E1 (PGE1) treatment, which produces clinical benefits in PAOD, might decrease such levels. METHODS: Eight patients with PAOD at Fontaine stage II to IV were treated with a daily intravenous infusion of 10 microg of PGE1 for 7 consecutive days. Blood samples before and after 7-day PGE1 treatment were used for assays of MCP-1, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), von Willebrand factor (vWF), and endothelin-1 (ET-1). RESULTS: Serum MCP-1 levels in patients with PAOD were significantly higher than those in healthy control subjects (263.8 +/- 52.8 vs 136.5 +/- 15.0 pg/mL, P =.002). PGE1 administration for 7 days resulted in a significant decrease in the MCP-1 level, from 263.8 +/- 52.8 to 196.1 +/- 25.5 pg/mL (P =.02), whereas levels of IL-6, hs-CRP, and ET-1 and the activity of vWF were not affected. CONCLUSIONS: Serum MCP-1 levels were elevated in patients with PAOD, indicating the involvement of activation of monocytes in the pathogenesis of this disorder. Parenteral administration of PGE1 appeared to decrease circulating MCP-1 levels, which might lead to the suppression of the development of atherosclerotic lesions in patients with PAOD.

Adult↗
PubMed2003

Inhibition of the renin-angiotensin system: no effect on circulating macrophage colony-stimulating factor levels in acute myocardial infarction.

Macrophage colony-stimulating factor, which induces proliferation and differentiation, and activation of monocytes and macrophages, plays an important role in the vulnerability of atheromatous plaques as well as the formation of atherosclerotic lesions. We measured serum concentrations of macrophage colony-stimulating factor in patients with acute myocardial infarction and also investigated the effects of early administration of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker on circulating macrophage colony-stimulating factor levels in these patients. The patients were divided randomly into 3 therapeutic groups; perindopril, candesartan, and control (without perindopril and candesartan) groups, and the drugs were administered within 24 to 36 hours after the onset of acute myocardial infarction. Serum macrophage colony-stimulating factor concentrations in acute myocardial infarction patients at the time of admission were significantly higher than those in healthy control subjects. The macrophage colony-stimulating factor levels in the patients decreased gradually after admission, but remained significantly higher than those in control subjects for 14 days. There were no significant differences in serum macrophage colony-stimulating factor levels among the 3 therapeutic groups during this study period. In conclusion, circulating macrophage colony-stimulating factor levels are elevated during the course of acute myocardial infarction, and inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitor or angiotensin receptor blocker does not affect these levels.

Adult↗
PubMed2003

Serum concentrations of vascular endothelial growth factor and monocyte-colony stimulating factor in peripheral arterial disease.

Vascular endothelial growth factor (VEGF) strongly promotes angiogenesis, and monocyte-colony stimulating factor (M-CSF) regulates the differentiation, proliferation, and survival of monocytes. Both VEGF and M-CSF are expressed in atherosclerotic lesions. The present study was performed to clarify the role of VEGF and M-CSF in the development of peripheral artery disease (PAD). The serum VEGF and M-CSF concentrations were determined in patients with arteriosclerosis obliterans (ASO) and thromboangitis obliterans (TAO). In both patient groups the serum VEGF concentrations were significantly higher than those in the control subjects. In contrast, the serum M-CSF concentrations in the ASO patients were significantly higher than those in both the TAO patients and control subjects, but there were no differences in the M-CSF concentrations between the TAO patients and control subjects. There was no correlation between the serum concentrations of VEGF and M-CSF. In conclusion, the serum VEGF concentration was increased in ASO and TAO patients, but increased concentration of M-CSF was seen only in ASO patients. These results may reflect a difference between ASO and TAO in disease pathogenesis.

Arteriosclerosis Obliterans↗
PubMed2003

Primary cutaneous diffuse large B cell lymphoma: a clinically aggressive case.

An 80-year-old woman was diagnosed with primary cutaneous B cell lymphoma. She had multifocal cutaneous tumors, but no nodal lymphadenopathy or bone marrow involvement. Histopathological examination of a biopsy specimen showed diffuse large B cell lymphoma without a bcl-2 expression. Complete resolution of hypercalcemia and disappearance of tumors were achieved with CHOP therapy, but a rapidly progressive skin lesion was observed soon after the completion of the therapy. The clinical manifestation of primary cutaneous diffuse large B cell lymphoma is diverse and the treatment strategy is not entirely clarified. This case represents another example of this rare lymphoma.

Aged↗
PubMed2003

Abnormal nocturnal blood pressure falls in elderly hypertension: clinical significance and determinants.

Abnormal patterns of diurnal blood pressure variation have been reported to be related to advanced target organ damage and poor cardiovascular prognosis. We studied silent cerebrovascular disease and stroke events in older Japanese patients with different nocturnal blood pressure dipping. There was a J-shaped relationship of nocturnal dipping status with silent cerebral infarcts detected by brain magnetic resonance imaging at baseline, and with stroke incidence during the follow-up period. The extreme-dippers (with marked nocturnal blood pressure dipping) and the risers (with higher nocturnal blood pressure than awake blood pressure) had a higher prevalence of silent cerebral infarcts and a poorer stroke prognosis than those with appropriate nocturnal blood pressure dipping (dippers). The extreme-dippers tended to have predominant systolic hypertension and increased blood pressure variability. Several factors affect the diurnal blood pressure variation pattern. The non-dipping pattern is associated with autonomic nervous dysfunction and poor sleep quality due to nocturnal behavior and sleep apnea. The extreme-dippers might have increased arterial stiffness with reduced circulating blood volume in addition to an excessive morning surge due to alpha-adrenergic hyperactivity. Anti-hypertensive medication that normalizes the diurnal blood pressure variation might improve the cardiovascular prognosis in high-risk hypertensive patients.

Aged↗
PubMed2002

Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial.

BACKGROUND: Preclinical studies have established that implantation of bone marrow-mononuclear cells, including endothelial progenitor cells, into ischaemic limbs increases collateral vessel formation. We investigated efficacy and safety of autologous implantation of bone marrow-mononuclear cells in patients with ischaemic limbs because of peripheral arterial disease. METHODS: We first did a pilot study, in which 25 patients (group A) with unilateral ischaemia of the leg were injected with bone marrow-mononuclear cells into the gastrocnemius of the ischaemic limb and with saline into the less ischaemic limb. We then recruited 22 patients (group B) with bilateral leg ischaemia, who were randomly injected with bone marrow-mononuclear cells in one leg and peripheral blood-mononuclear cells in the other as a control. Primary outcomes were safety and feasibility of treatment, based on ankle-brachial index (ABI) and rest pain, and analysis was per protocol. FINDINGS: Two patients were excluded from group B after randomisation. At 4 weeks in group B patients, ABI was significantly improved in legs injected with bone marrow-mononuclear cells compared with those injected with peripheral blood-mononuclear cells (difference 0.09 [95% CI 0.06-0.11]; p<0.0001). Similar improvements were seen for transcutaneous oxygen pressure (13 [9-17]; p<0.0001), rest pain (-0.85 [-1.6 to -0.12]; p=0.025), and pain-free walking time (1.2 [0.7-1.7]; p=0.0001). These improvements were sustained at 24 weeks. Similar improvements were seen in group A patients. Two patients in group A died after myocardial infarction unrelated to treatment. INTERPRETATION: Autologous implantation of bone marrow-mononuclear cells could be safe and effective for achievement of therapeutic angiogenesis, because of the natural ability of marrow cells to supply endothelial progenitor cells and to secrete various angiogenic factors or cytokines.

Aged↗
PubMed2002

U-curve relationship between orthostatic blood pressure change and silent cerebrovascular disease in elderly hypertensives: orthostatic hypertension as a new cardiovascular risk factor.

OBJECTIVES: The study investigated the clinical significance and mechanism of orthostatic blood pressure (BP) dysregulation in elderly hypertensive patients. BACKGROUND: Although orthostatic hypotension (OHYPO), often found in elderly hypertensive patients, has been recognized as a risk factor for syncope and cardiovascular disease, both the clinical significance and the mechanism of orthostatic hypertension (OHT) remain unclear. METHODS: We performed a head-up tilting test and brain magnetic resonance imaging (MRI) in 241 elderly subjects with sustained hypertension as indicated by ambulatory BP monitoring. We classified the patients into an OHT group with orthostatic increase of systolic blood pressure (SBP) of >or=20 mm Hg (n = 26), an OHYPO group with orthostatic SBP decrease of >or=20 mm Hg (n = 23), and a normal group with neither of these two patterns (n = 192). RESULTS: Silent cerebral infarcts were more common in the OHT (3.4/person, p < 0.0001) and OHYPO groups (2.7/person, p = 0.04) than in the normal group (1.4/person). Morning SBP was higher in the OHT group than in the normal group (159 vs. 149 mm Hg, p = 0.007), while there were no significant differences of these ambulatory BPs between the two groups during other periods. The OHT (21 mm Hg, p < 0.0001) and OHYPO (20 mm Hg, p = 0.01) groups had higher BP variability (standard deviation of awake SBP) than the normal group (17 mm Hg). The associations between orthostatic BP change and silent cerebrovascular disease remained significant after controlling for confounders, including ambulatory BP. The orthostatic BP increase was selectively abolished by alpha-adrenergic blocking, indicating that alpha-adrenergic activity is the predominant pathophysiologic mechanism of OHT. CONCLUSIONS: Silent cerebrovascular disease is advanced in elderly hypertensives having OHT. Elderly hypertensives with OHT or OHYPO may have an elevated risk of developing hypertensive cerebrovascular disease.

Adrenergic alpha-Antagonists↗