Hypertension: Watanabe H

Watanabe H. · No affiliation provided · Intern Med. · Pubmed #15575233 links to  free full text

This publication has no abstract.

Watanabe H, Murakami M, Ohba T, Takahashi Y, Ito H. · Second Department of Internal Medicine, Akita University School of Medicine 1-1-1, Hondoh, Akita 010-8543, Japan. · Pharmacol Ther. · Pubmed #18508125 No free full text.

Abstract: The transient receptor potential (TRP) channel superfamily consists of 28 mammalian cation channels and is expressed in almost every tissue, including the heart and vasculature; most TRP channels are permeable to Ca(2+) and are prime molecular candidates for store-operated channels (SOCs), receptor-operated channels (ROCs), ligand-gated channels (LGCs) and stretch-activated channels (SACs). As these channels act as multifunctional cellular sensors and are involved in several fundamental cell functions such as contraction, proliferation and cell death, investigation of their roles in human disease is very important. This review presents an overview of current knowledge about the pathological role of TRP channels in cardiovascular diseases and highlights some TRP channels for which a role in the diseases can be anticipated. Evidences suggest that up-regulation of TRPC channels is involved in the development of cardiac hypertrophy and heart failure; TRPM4 participates in some features of cardiac arrhythmias; increased expression of TRPC channels is associated with vascular remodeling and pulmonary hypertension; reduced expression or activity of TRPV4 impairs endothelium-dependent vasorelaxation; TRPC3/C4 and TRPM2 act as endothelial redox sensors; and TRPC1, -C4, -C6, -V4, and -M2, have been implicated in endothelial barrier dysfunction. Ultimately, TRP channels will become important novel pharmacological targets for the treatment of human cardiovascular diseases.

Zeng C, Sanada H, Watanabe H, Eisner GM, Felder RA, Jose PA. · Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China. · Physiol Genomics. · Pubmed #15548830 links to  free full text

Abstract: Abnormalities in dopamine production and receptor function have been described in human essential hypertension and rodent models of genetic hypertension. Under normal conditions, D(1)-like receptors (D(1) and D(5)) inhibit sodium transport in the kidney and intestine. However, in the Dahl salt-sensitive and spontaneously hypertensive rats (SHRs) and in humans with essential hypertension, the D(1)-like receptor-mediated inhibition of epithelial sodium transport is impaired because of an uncoupling of the D(1)-like receptor from its G protein/effector complex. The uncoupling is receptor specific, organ selective, nephron-segment specific, precedes the onset of hypertension, and cosegregates with the hypertensive phenotype. The defective transduction of the renal dopaminergic signal is caused by activating variants of G protein-coupled receptor kinase type 4 (GRK4: R65L, A142V, A486V). The GRK4 locus is linked to and GRK4 gene variants are associated with human essential hypertension, especially in salt-sensitive hypertensive subjects. Indeed, the presence of three or more GRK4 variants impairs the natriuretic response to dopaminergic stimulation in humans. In genetically hypertensive rats, renal inhibition of GRK4 expression ameliorates the hypertension. In mice, overexpression of GRK4 variants causes hypertension either with or without salt sensitivity according to the variant. GRK4 gene variants, by preventing the natriuretic function of the dopaminergic system and by allowing the antinatriuretic factors (e.g., angiotensin II type 1 receptor) to predominate, may be responsible for salt sensitivity. Subclasses of hypertension may occur because of additional perturbations caused by variants of other genes, the quantitative interaction of which may vary depending upon the genetic background.

Ihara S, Shimamoto K, Watanabe H, Sakai R, Kawana M. · Department of Cardiology, Aoyama Hospital, Tokyo Women's Medical University, Japan. · Hypertens Res. · Pubmed #17283868 No free full text.

Abstract: Obesity is often complicated by hypertension, and both conditions are risk factors for atherosclerosis. Leptin has attracted attention as a possible cause of hypertension in obese persons. We investigated the effect of a slow-release alpha1-receptor blocker, bunazosin hydrochloride, on leptin levels and insulin resistance in obese hypertensive patients with hyperleptinemia. The subjects were 17 patients (12 men and 5 women aged 56.1 +/- 12.2 years) with essential hypertension who were not receiving alpha1-receptor blockers. They had a body mass index (BMI) > or = 25 kg/m2 and a plasma leptin concentration > or = 5 ng/ml. They received oral therapy with bunazosin hydrochloride at doses of up to 9 mg/day. The plasma leptin concentration, body weight, blood pressure, heart rate, fasting blood glucose, plasma insulin concentration, and free fatty acid level were compared between before and after treatment. Although there was no significant change of BMI, there was a significant decrease of plasma leptin after treatment (10.6 +/- 5.4 ng/ml vs. 8.7 +/- 3.4 ng/ml, p = 0.0128), as well as a significant decrease of plasma insulin (9.8 +/- 4.8 microU/ml vs. 8.1 +/- 4.6 microU/ml, p = 0.0494) and HOMA-R (2.9 +/- 2.1 vs. 2.2 +/- 1.5, p = 0.0237). In conclusion, bunazosin hydrochloride reduced the plasma leptin level and improved insulin resistance in hypertensive patients with obesity and hyperleptinemia.

Nishio S, Watanabe H, Kosuge K, Uchida S, Hayashi H, Ohashi K. · Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. · Hypertens Res. · Pubmed #16097365 No free full text.

Abstract: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are often prescribed in association with antihypertensive agents, including calcium antagonists. Simvastatin is an HMG-CoA reductase inhibitor that is metabolized by the cytochrome P450 (CYP) 3A4. The calcium antagonist amlodipine is also metabolized by CYP3A4. The purpose of this study was to investigate drug interactions between amlodipine and simvastatin. Eight patients with hypercholesterolemia and hypertension were enrolled. They were given 4 weeks of oral simvastatin (5 mg/day), followed by 4 weeks of oral amlodipine (5 mg/day) co-administered with simvastatin (5 mg/day). Combined treatment with simvastatin and amlodipine increased the peak concentration (C(max)) of HMG-CoA reductase inhibitors from 9.6 +/- 3.7 ng/ml to 13.7 +/- 4.7 ng/ml (p < 0.05) and the area under the concentration-time curve (AUC) from 34.3 +/- 16.5 ng h/ml to 43.9 +/- 16.6 ng h/ml (p < 0.05) without affecting the cholesterol-lowering effect of simvastatin. This study is the first to determine prospectively the pharmacokinetic and pharmacodynamic interaction between amlodipine and simvastatin.

Watanabe H, Kosuge K, Nishio S, Yamada H, Uchida S, Satoh H, Hayashi H, Ishizaki T, Ohashi K. · Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. · Life Sci. · Pubmed #15531380 No free full text.

Abstract: Pharmacokinetic and pharmacodynamic interactions between simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and diltiazem, a calcium antagonist, were investigated in 7 male and 4 female patients with hypercholesterolemia and hypertension. The patients were given, for one in a three consecutive 4-week periods, oral simvastatin (5 mg/day), oral simvastatin (5 mg/day) combined with diltiazem (90 mg/day), and then oral diltiazem (90 mg/day), respectively. The area under the plasma concentration versus time curve up to 6 hours post-dose (AUC0-6h) and maximum plasma concentrations (Cmax) of the drugs, serum lipid profiles, blood pressures and liver functions were assessed on the last day of each of the three 4-week periods. After the combined treatment period, Cmax of HMG-CoA reductase inhibitor was elevated from 7.8 +/- 2.6 ng/ml to 15.4 +/- 7.9 ng/ml (P < 0.01) and AUC0-6h from 21.7 +/- 4.9 ng x hr/ml to 43.3 +/- 23.4 ng x hr/ml (P < 0.01), while Cmax of diltiazem was decreased from 74.2 +/- 36.4 ng/ml to 58.6 +/- 18.9 ng/ml (P < 0.05) and its AUC0-6h from 365 +/- 153 ng x hr/ml to 287 +/- 113 ng x hr/ml (P < 0.01). Compared to simvastatin monotherapy, combined treatment further reduced LDL-cholesterol levels by 9%, from 129 +/- 16 mg/dl to 119 +/- 17 mg/dl (P < 0.05). No adverse events were observed throughout the study. These apparent pharmacokinetic interactions, namely the increase of HMG-CoA reductase inhibitor concentration by diltiazem and the decrease of diltiazem concentration by simvastatin, enhance the cholesterol-lowering effects of simvastatin during combined treatment.

Totsuka M, Miyashita Y, Ito Y, Oyama T, Hashiguti S, Watanabe H, Shirai K, Ban T, Ishihara H, Yamamoto K, Kawano E, Mori J, Kanechi M. · Department of Internal Medicine and Clinical Laboratory Medicine, Toho University, Sakura Hospital. · Nippon Ronen Igakkai Zasshi. · Pubmed #11431890 No free full text.

Abstract: Recently, much attention has been paid to small sized low density lipoprotein (LDL) as a risk factor for ischemic heart disease. We investigated the effect of celiprolol hydrochloride (CH), which is a beta 1 selective beta-blocker with high intrinsic sympathomimetic activity (ISA), on the LDL particle size. We treated 41 hypertensive patients with CH and studied the change in LDL particle size according to the score of fast beta lipoprotein and LDL relative mobility value (LDL-Rm) measured by lipoprotein polyacrylamide gel disc electrophoresis (PAGE). We also studied changes in blood pressure, total cholesterol (TC), trygiyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and midband on PAGE. Systolic and dyastolic blood pressure and pulse significantly decreased during treatment. TC levels were significantly decreased at 8 weeks in all subjects and at 4, 8 and 12 weeks in patients with a TC value of over 220 mg/dl. TG levels were significantly decreased at 4 and 8 weeks in patients with initial levels of over 150 mg/dl, and significantly increased at 4 and 8 weeks in those with initial levels of under 150 mg/dl of TG. HDL-C levels did not significantly change during treatment. LDL-C levels were significantly decreased at 4, 8 and 12 weeks in patients with initial levels of over 150 mg/dl. Apo AI, AII, B, CII, CIII and E levels did not significantly change during treatment. Fast beta lipoprotein scores did not significantly change overall during treatment, but were significantly decreased at 4 and 8 weeks in patients initial TG levels of over 150 mg/dl and at 4 and 12 weeks in those with initial levels of over 220 mg/dl of TC. LDL-Rm scores did not significantly change during treatment. Midband scores were significantly reduced overall at 8 weeks, and after 4 and 8 weeks in patients with initial TG levels of over 150 mg/dl and at 4, 8 and 12 weeks in those with initial TC levels of over 220 mg/dl. These results indicated that CH did not change LDL particle size. It was suggested that CH might be a beneficial beta-blocker from the standpoint of prevention for atherosclerosis.

Ueno T, Watanabe H, Fukuda N, Tsunemi A, Tahira K, Matsumoto T, Takayama T, Chiku M, Saito S, Sato Y, Hirayama A, Matsumoto K, Soma M. · Department of Medicine, Division of Nephrology, Hypertension and Endocrinology, Nihon University School of Medicine, Tokyo, Japan. · Med Sci Monit. · Pubmed #19564823 No free full text.

Abstract: BACKGROUND: Previous studies have shown that oxidative stress plays an important role in coronary heart disease. Polymorphisms in key enzymes that regulate oxidative stress may play a role in atherogenicity and were investigated in this study. MATERIAL/METHODS: One hundred and forty-three patients with angiographically proven coronary artery disease were studied. The effect of the C242T polymorphism of the p22phox gene, an essential component of the NADH/NADPH oxidase, and glutathione-S-transferase T1, M1 and P1 polymorphisms on plasma MDA-LDL, soluble CD40 ligand, E-selectin and soluble ICAM1 levels was determined. Genotyping of the p22 phox C242T polymorphism was performed by RFLP analysis, and GSTT1, GSTM1 and GSTP1 genotypes were determined using a multiplex PCR assay. The MDA-LDL, sCD40L, E-selectin and sICAM1 levels were determined using ELISA. RESULTS: Patients with the TT or TC genotype of the p22 phox C242T polymorphism had significantly higher plasma MDA-LDL levels compared to those of the CC genotype. Plasma E-selectin and soluble ICAM1 levels were significantly higher in the TT or TC genotype compared to that of the CC genotype. In GSTT1+ patients, plasma MDA-LDL levels were significantly higher than those of GSTT1- patients. CONCLUSIONS: Genetic polymorphism of the p22 phox gene had a significant effect on plasma lipid peroxidation and endothelial function through oxidative stress. The results of this study confirm the effect of NADH/NADPH oxidase on atherogenecity.

Saito T, Nishise Y, Makino N, Haga H, Ishii R, Okumoto K, Ito JI, Watanabe H, Saito K, Takeda H, Togashi H, Kubota I, Daimon M, Kato T, Kawata S. · Department of Gastroenterology, Yamagata University School of Medicine, Yamagata 990-9585, Japan. · Metabolism. · Pubmed #19411086 No free full text.

Abstract: Measurement of the serum alanine aminotransferase (ALT) level is used as an initial test for detection of liver diseases, and recent studies have also highlighted its potential value as a measure of overall health and survival as a marker of an increased risk of metabolic disorder. This study was designed to clarify the prevalence of elevated ALT levels in the Japanese population and to assess factors associated with ALT elevation. The subjects were 2165 individuals aged 40 to 85 years who participated in a Japanese community-based study referred to as the Takahata Study. Serum ALT levels and factors associated with ALT elevation were investigated. Among 2087 subjects who were negative for hepatitis B and C, the rates of elevated ALT greater than 30 U/L in men and greater than 25 U/L in women were 217 (22.7%) of 957 and 239 (21.2%) of 1130, respectively. These ALT cutoff levels had a specificity of more than 80% for exclusion of subjects with none or 1 of 3 metabolic risk factors: hypertension, lipid metabolism abnormality, and hyperglycemia. Multivariate analysis revealed 5 factors with a significant association with ALT elevation in men (n = 957): high gamma-glutamyltranspeptidase, low adiponectin, high low-density lipoprotein cholesterol, high body mass index, and high homeostasis model assessment insulin resistance index. Similarly, 4 factors were significantly associated with ALT elevation in women (n = 1130): high gamma-glutamyltranspeptidase, low adiponectin, high body mass index, and high homeostasis model assessment insulin resistance index. These results suggest that elevated ALT levels in the Japanese population older than 40 years have a strong association with metabolic syndrome-related features including obesity and insulin resistance.

Koyama T, Ono K, Watanabe H, Ohba T, Murakami M, Iino K, Ito H. · Department of Cardiology, Akita University School of Medicine, Akita, Japan. · Circ J. · Pubmed #19110506 links to  free full text

Abstract: BACKGROUND: Atrial arrhythmia is often encountered in chronic pulmonary disease with pulmonary hypertension (PH), but few studies have investigated the electrical remodeling of atrial Ca(2+) channels under PH. METHODS AND RESULTS: Wistar rats were injected with monocrotaline (MCT), resulting in PH with right atrial and ventricular hypertrophy. The L-type Ca(2+) channel current density was significantly decreased in right atrial cells of MCT-treated rats, accompanied by a significant reduction in mRNA expression of the CaV1.2 (alpha(1C)) subunit and accessory beta(2) subunit. Conversely, the low voltage-activated Ca(2+) current was more marked in the right atrial cells of MCT-treated rats than in those of control rats. The current-voltage relationship and the time course of inactivation closely resembled those of T-type Ca(2+) channels, although the current was only slightly inhibited by 10-100 micromol/L Ni(2+). No significant differences were observed in the mRNA expression levels of CaV3.1 (alpha(1G)) and CaV3.2 (alpha(1H)) or the protein level of the CaV3.1 subunit. In left atrial cells, the electrophysiological molecular properties of Ca(2+) channels were unaffected by MCT treatment. CONCLUSIONS: PH causes right atrial hypertrophy, associated with alteration of the electrophysiological molecular properties of Ca(2+) channels.

Oki K, Yamane K, Sakashita Y, Kamei N, Watanabe H, Toyota N, Shigeta M, Sasano H, Kohno N. · Department of Molecular and Internal Medicine, Division of Clinical Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Hiroshima, Hiroshima, 734-8551, Japan. · Clin Exp Nephrol. · Pubmed #18543063 No free full text.

Abstract: A 50-year-old male patient with a 15-year history of hypertension was referred to our hospital for evaluation of bilateral adrenal tumors. No Cushingoid features were observed. Computed tomographic scan showed 10-mm masses in each adrenal gland. Preoperative endocrinological examinations revealed autonomous cortisol and aldosterone secretion in this patient. The results of a subsequent adrenal venous catheterization study were consistent with the presence of a left cortisol-producing tumor and a right aldosterone-producing tumor. A left partial adrenalectomy was performed initially, but cortisol and aldosterone over-secretion persisted. Accordingly, the patient underwent a right adrenalectomy. Pathological examination of the resected specimens, including immunohistochemical analysis, demonstrated that both adenomas possibly produced cortisol and aldosterone. This is an extremely rare case of bilateral adrenal tumors, in which the left adrenocortical tumor produced and secreted cortisol or both cortisol and aldosterone and the right one produced and secreted both aldosterone and cortisol, as confirmed by clinical findings and pathological studies using immunohistochemical analysis.

Honma F, Shio K, Monoe K, Kanno Y, Takahashi A, Yokokawa J, Kobayashi H, Watanabe H, Irisawa A, Ohira H. · Department of Internal Medicine II, Fukushima Medical University School of Medicine, Japan. · Intern Med. · Pubmed #18379158 links to  free full text

Abstract: A 68-year-old woman was admitted to a hospital with pulmonary hypertension (PH) in August 2006. Perfusion scintigraphy of the lung was normal and showed no interstitial change. Liver dysfunction was noted and antinuclear antibodies (x1,280) were positive. In November 2006, muscle pain and weakness gradually developed in the brachial muscle and a quadriceps. She was referred and admitted to our hospital for elevated CPK and liver dysfunction in March 2007. She was diagnosed with polymyositis (PM) on the basis of the histological findings of muscle biopsy and treated with prednisolone. In addition, because anti-centromere antibodies and anti-mitochondrial M2 antibodies were positive with high titers, she was also diagnosed with primary biliary cirrhosis (PBC). Although PBC is often associated with other autoimmune diseases, there have been no reports of PBC complicated by PM and PH.

Watanabe H, Tanabe N, Watanabe T, Darbar D, Roden DM, Sasaki S, Aizawa Y. · Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. · Circulation. · Pubmed #18285562 links to  free full text

Abstract: BACKGROUND: The metabolic syndrome consists of a cluster of atherosclerotic risk factors, many of which also have been implicated in the genesis of atrial fibrillation (AF). However, the precise role of the metabolic syndrome in the development of AF is unknown. METHODS AND RESULTS: This prospective, community-based, observational cohort study was based on an annual health check-up program in Japan. We studied 28 449 participants without baseline AF. We used 2 different criteria for the metabolic syndrome--the guidelines of the National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATP III) and those of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI)--to study the risk of development of new-onset AF. The metabolic syndrome was present in 3716 subjects (13%) and 4544 subjects (16%) using the NCEP-ATP III and AHA/NHLBI definitions, respectively. During a mean follow-up of 4.5 years, AF developed in 265 subjects (105 women). Among the metabolic syndrome components, obesity (age- and sex-adjusted hazard ratio [HR], 1.64), elevated blood pressure (HR, 1.69), low high-density lipoprotein cholesterol (HR, 1.52), and impaired insulin tolerance (HR, 1.44 [NCEP-ATP III] and 1.35 [AHA/NHLBI]) showed an increased risk for AF. The association between the metabolic syndrome and AF remained significant in subjects without treated hypertension or diabetes by the NCEP-ATP III definition (HR, 1.78) but not by the AHA/NHLBI definition (HR, 1.28). CONCLUSIONS: The metabolic syndrome was associated with increased risk of AF. The metabolic derangements of the syndrome may be important in the pathogenesis of AF.

Hayashi T, Kawashima S, Itoh H, Yamada N, Sone H, Watanabe H, Hattori Y, Ohrui T, Yoshizumi M, Yokote K, Kubota K, Nomura H, Umegaki H, Iguchi A, Anonymous00216. · Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho,Showa-ku, Nagoya 466-8550, Japan. · Circ J. · Pubmed #18219157 links to  free full text

Abstract: BACKGROUND: The respective incidences of ischemic heart and cerebrovascular disease (IHD, CVD) are high in diabetic individuals. Complications of dyslipidemia increase the risk, but direct evidence is limited, so a cohort prospective study (Japan-CDM) was conducted. METHODS AND RESULTS: The study group comprised 4,014 subjects with type 2 diabetes (1,936 women, 2,078 men; mean age 67.4+/-9.5 years) who were divided into dyslipidemic patients (79.1%) with or without medication (medicated, 50.9%; not medicated, 28.2%) and normo-lipidemic patients (20.9%). The incidence of IHD, CVD, arteriosclerosis obliterans (ASO), congestive heart failure (CHF) and death was assessed. IHD and CVD occurred in 0.82 and 0.67%, respectively, during the first year following registration. CHF, ASO and sudden death occurred in 0.27%, 0.12% and 0.12%, respectively. There was a significant statistical difference in the relation of elevated levels of high-density lipoprotein-cholesterol to lower rates of IHD and CVD. IHD and CVD in males were dependent on the level of low-density lipoprotein-cholesterol (LDL-C): 0.45%, 1.56%, 1.78%, 1.91% and 2.34% were observed in less than 2.11, 2.11-2.62, 2.63-3.15, 3.16-3.67, and more than 3.68 mol/L of LDL-C. In the lowest LDL-C group, death other than from vascular diseases was increased. Age, sex (male) and complicated hypertension increased the risk of events. Patients who were prescribed antihyperlipidemic agents suffered less events than patients who were not being treated, which suggests direct effects of therapy. CONCLUSION: Strict lipid control may be effective for reducing the incidence of vascular events in Japanese diabetic individuals.

Watanabe H, Kashimoto N, Kajimura J, Kamiya K. · Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. · Hypertens Res. · Pubmed #17249529 No free full text.

Abstract: The purpose of this study was to compare the effects of miso and sodium chloride (NaCl) on blood pressure in both sexes of Dahl and SD rats. The systolic and diastolic blood pressures (SBP/DBP) were measured at 2, 4, 8 and 12 weeks of treatment with a miso diet including 2.3% NaCl, a high-sodium diet including 2.3% or 1.9% NaCl, or a normal diet including 0.3% NaCl (MF diet; Oriental Yeast Co., Tokyo, Japan). The rats were autopsied after 12 weeks on a diet. DBP in male Dahl rats was significantly increased by the 2.3% NaCl diet as compared with that in the MF group (p < 0.01) or miso group (p < 0.05) from 4 weeks of treatment. Thereafter, SBP and DBP in both the high NaCl groups were significantly increased when compared with the MF or miso group. SBP in female Dahl rats on 2.3% NaCI was significantly increased from 8 weeks after treatment. Nephropathy was observed in both sexes of Dahl rats but not SD rats. These results show that blood pressure was not increased by the miso diet.

Hussein G, Nakagawa T, Goto H, Shimada Y, Matsumoto K, Sankawa U, Watanabe H. · International Research Center for Traditional Medicine, Toyama, Toyama Prefecture 939-8224, Japan. · Life Sci. · Pubmed #17074368 No free full text.

Abstract: Glucose and lipid metabolic parameters play crucial roles in metabolic syndrome and its major feature of insulin resistance. This study was designed to investigate whether dietary astaxanthin oil (ASX-O) has potential effects on metabolic syndrome features in an SHR/NDmcr-cp (cp/cp) rat model. Oral administration of ASX (50 mg/kg/day) for 22 weeks induced a significant reduction in arterial blood pressure in SHRcp. It also significantly reduced the fasting blood glucose level, homeostasis index of insulin resistance (HOMA-IR), and improved insulin sensitivity. The results also showed an improved adiponectin level, a significant increase in high-density lipoprotein cholesterol, a significant decrease in plasma levels of triglycerides, and non-esterified fatty acids. Additionally, ASX showed significant effects on the white adipose tissue by decreasing the size of the fat cells. These results suggest that ASX ameliorates insulin resistance by mechanisms involving the increase of glucose uptake, and by modulating the level of circulating lipid metabolites and adiponectin.

Watanabe H, Tanabe N, Makiyama Y, Chopra SS, Okura Y, Suzuki H, Matsui K, Watanabe T, Kurashina Y, Aizawa Y. · Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232-0575, USA. · Am Heart J. · Pubmed #16996849 No free full text.

Abstract: BACKGROUND: Left ventricular hypertrophy is a known risk factor for atrial fibrillation (AF). However, it is not well understood whether other electrocardiogram abnormalities are associated with development of AF. METHODS: This was a community-based cohort study based upon a database of annual health examinations. We included 63,386 subjects aged > or = 50 years, without baseline AF (including atrial flutter), structural heart disease, or heart failure, who completed the annual examination during a 10-year follow-up period (1991-2002). The electrocardiographic risk factors for AF were studied in the subjects. RESULTS: Atrial fibrillation developed in 873 subjects. Age, male sex, body mass index, hypertension, systolic and diastolic blood pressure, and diabetes were significant risk factors for the development of AF. In multivariable logistic regression analysis adjusted for these risk factors, electrocardiographic left ventricular hypertrophy (odds ratio [OR], 1.43), ST-segment abnormality without left ventricular hypertrophy (OR, 1.89), and the presence of premature complexes during a 10-second recording (OR, 2.89) were significantly associated with AF, whereas either right (OR, 0.84) or left bundle branch block (OR, 0.96) was unrelated. The risk for AF increased progressively with the severity of both ST-segment change and premature complexes. CONCLUSIONS: ST-segment abnormality and comparably high-frequency premature complexes were each associated with increased risk for the development of AF. These electrocardiographic findings may be useful to stratify high-risk subjects for new-onset AF.

Iwadate H, Kobayashi H, Shio K, Noguchi E, Watanabe K, Sasajima T, Sekine H, Watanabe H, Ohira H, Obara K, Sato Y. · Department of Internal Medicine II, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan. · Mod Rheumatol. · Pubmed #16633932 No free full text.

Abstract: We describe a 49-year-old woman who presented in 2002 with pure red cell aplasia (PRCA), systemic lupus erythematosus (SLE), and idiopathic portal hypertension (IPH) that developed following a thymectomy. She underwent a thymectomy at 40 years of age to treat myasthenia gravis. PRCA developed 3 years after the thymectomy and she was successfully treated with cyclosporin. Systemic lupus erythematosus and IPH were diagnosed 6 years later. We conclude that immunological dysfunction resulting from the thymectomy contributed significantly to the subsequent development of PRCA, SLE, and IPH in this patient. This is the first report to describe this extremely rare occurrence.

Sasajima T, Suzuki T, Mori K, Ichii O, Tai M, Ochiai H, Ejiri Y, Watanabe H, Ohira H, Obara K, Sato Y. · Department of Internal Medicine II, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan. · Mod Rheumatol. · Pubmed #16633928 No free full text.

Abstract: A 53-year-old woman who had been diagnosed with rheumatoid arthritis was found to have thrombocytopenia, splenomegaly, and gastric varices. She was diagnosed as having idiopathic portal hypertension on the basis of liver biopsy and angiography. Treatment with prednisolone was not sufficiently effective for thrombocytopenia. After transabdominal devascularization with splenectomy, thrombocytopenia subsided and gastric varices disappeared. In this case, the autoimmune mechanism as well as hypersplenism was suspected of being involved in the mechanism of thrombocytopenia.

Hussein G, Goto H, Oda S, Sankawa U, Matsumoto K, Watanabe H. · International Research Center for Traditional Medicine, Toyama Prefecture, Japan. · Biol Pharm Bull. · Pubmed #16595899 links to  free full text

Abstract: We investigated the effects of a dietary astaxanthin (ASX-O) on oxidative parameters in spontaneously hypertensive rats (SHR), by determination of the level of nitric oxide (NO) end products nitrite/nitrate (NO2-/NO3-) and lipid peroxidation in ASX-O-treated SHR. Oral administration of the ASX-O significantly reduced the plasma level of NO2-/NO3- compared to the control vehicle (p<0.05). The lipid peroxidation level, however, was reduced in both ASX-O- and olive oil-treated groups. We also analyzed the post-treatment effects of ASX-O on the vascular tissues by examining the changes in the aorta and coronary arteries and arterioles. The dietary ASX-O showed significant reduction in the elastin bands in the rat aorta (p<0.05). It also significantly decreased the [wall : lumen] aerial ratio of the coronary arteries. These results suggest that ASX-O can modulate the oxidative condition and may improve vascular elastin and arterial wall thickness in hypertension.

Nakazato K, Watanabe H, Kawana K, Hiraoka T, Kiuchi T, Oshika T. · Division of Ophthalmology, Kinu Medical Association Hospital, Mitsukaido, Japan. · Ophthalmologica. · Pubmed #16286791 No free full text.

Abstract: PURPOSE: To assess the arterial stiffness in patients with branch retinal vein occlusion (BRVO). METHODS: Brachial-ankle pulse wave velocity (PWV) and ankle-brachial index were measured in 10 patients with BRVO (mean age 67.9 +/- 7.5 years) and in 18 age-matched controls (mean age 66.9 +/- 6.8 years). The controls were subjects with systemic essential hypertension having no retinal lesions. RESULTS: The PWV in the BRVO group was 1,946 +/- 254 cm/s which was significantly higher than that in the control group (1,688 +/- 274 cm/s; p = 0.014, Wilcoxon rank sum test). The ankle-brachial indexes were 1.16 and 1.15 in BRVO and control groups, respectively. There was no significant difference between the groups (p = 0.944). In the control group, there was a significant positive correlation between PWV and systolic blood pressure (Spearman correlation coefficient r(s) = 0.385, p = 0.043), while no significant correlation was found in the BRVO group (Spearman correlation coefficient r(s) = -0.188, p = 0.603). CONCLUSION: The arterial stiffness is increased in patients with BRVO which was thought to be due to the structural changes of the artery and not dependent on the blood pressure.

Watanabe H, Yasaki S, Horiuchi M, Takahashi Y. · Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine. · Nippon Ronen Igakkai Zasshi. · Pubmed #16117487 No free full text.

Abstract: A 75-year-old woman was admitted to our hospital because of sudden onset of paresis in her left arm and face. She had untreated hypertension and hyperlipidemia. When she came back home after playing with children in the park, she felt weakness in her left hand. On admission, physical examination revealed that her blood pressure was very high (200/102 mmHg). Only slight weakness in her left arm and left facial palsy were recognized neurologically. An electroencephalogram showed normal findings. Brain CT and MRI revealed a venous angioma near the right central sulcus. Gadolinium-DTPA enhanced MRI showed a group of small radiating veins (so called "the caput medusae sign") connected to the venous angioma. The remaining symptoms decreased with the normalization of blood pressure. It is suggested the intracranial motor tracts of the face and arm in the precentral gyrus are adjacent to the location of this venous angioma. The dilation of venous angioma due to high blood pressure was thought to cause the paresis of face and arm in this patient.

Aizawa Y, Kamimura N, Watanabe H, Aizawa Y, Makiyama Y, Usuda Y, Watanabe T, Kurashina Y. · Niigata University Graduate School of Medical and Dental Science Division of Cardiology, Japan. · Int J Cardiol. · Pubmed #16023231 No free full text.

Abstract: BACKGROUND: The accumulation of cardiovascular risk factors can be seen in a single person but it needs to be determined if this occurs more frequently than might be explained by mere coincidence. METHODS: This study involved 119,412 adults: 41,819 males and 77,593 females, who were 40 years of age or older and who underwent an annual health examination. From the clinical and biochemical data, the actual prevalence of a combination of 3 or more factors: abnormal body mass index (> or =25.0), hypertension, high triglyceride (> or =150 mg/dl), low HDL cholesterol (<40 mg/dl) and abnormal fasting glucose metabolism (fasting blood sugar > or =110 mg/dl or HbA1c. > or =5.5%) was determined. Then, the prevalence of a corresponding combination of 3-5 factors was predicted from the prevalence of each factor on the assumption that their combination occurs as a result of coincidence. RESULTS: The criteria of metabolic syndrome (> or =3 risk factors) was met in 17,842 (14.9%) of the examinees. The actual prevalence of any combination of 3-5 factors of metabolic syndrome was more frequent than those expected to occur by coincidence (P < 0.001). When compared with the prevalence of the total examinees, the prevalence of obesity and insulin resistance was 2.5 and 2.9 times higher in metabolic syndrome compared to that in the total examinees but it was 1.7 to 2.1 times higher in hypertension and high triglyceride. The former two were clustering more than hypertension or high triglyceride in metabolic syndrome. Abnormal levels of serum creatinine and total cholesterol were found more often in metabolic syndrome. CONCLUSION: Combinations of risk factors of metabolic syndrome were found more frequently than coincidental phenomenon in the subjects from the general population. These finding suggest that these risk factors do cluster and obesity and insulin resistance were suggested to be linked with metabolic syndrome more than hypertension or high triglyceride.

Hussein G, Goto H, Oda S, Iguchi T, Sankawa U, Matsumoto K, Watanabe H. · International Research Center for Traditional Medicine, Toyama Prefecture, Japan. · Biol Pharm Bull. · Pubmed #15930728 links to  free full text

Abstract: The current study was designed to determine the effects of a dietary astaxanthin (ASX-O) on vascular reactivity in spontaneously hypertensive rats (SHR), in order to verify its antihypertensive action mechanism. We evaluated contractions induced by phenylephrine (Phe), angiotensin II (Ang II) and the xanthine/xanthine oxidase (Xan/XOD) system, and relaxations induced by sodium nitroprusside (SNP) as well as endothelium-dependent relaxations mediated by acetylcholine (ACh) in thoracic aorta of the SHR, with and without ASX-O intervention. We also investigated the effects of ASX-O on blood rheology using a microchannel array system. In this study, ASX-O showed a significant modulatory effect on nitric oxide (NO)-induced vasorelaxation by the NO-donor SNP (p<0.05). However, it did not show significant effects in restoring the impaired endothelium-dependent relaxation to ACh in the SHR. On the other hand, the constrictive effects by Phe, Ang II and Xan/XOD were ameliorated by ASX-O (p<0.05). ASX-O also demonstrated significant hemorheological effect by decreasing the microchannel transit time of whole blood. In conclusion, the results suggest that ASX-O may act in modulating the blood fluidity in hypertension, and that the antihypertensive effects of ASX-O may be exerted through mechanisms including normalization of the sensitivity of the adrenoceptor sympathetic pathway, particularly [alpha]-adrenoceptors, and by restoration of the vascular tone through attenuation of the Ang II- and reactive oxygen species (ROS)-induced vasoconstriction.

Watanabe H, Katoh T, Eiro M, Iwamoto M, Ushikubi F, Narumiya S, Watanabe T. · Third Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan. · Circ J. · Pubmed #15635218 links to  free full text

Abstract: BACKGROUND: This study examined whether targeted disruption of the genes for the prostacyclin receptor (IP) or the thromboxane A2 receptor (TP) confers a susceptibility to salt-dependent hypertension. METHODS AND RESULTS: Eight female IP- or TP-deficient mice were examined. Baseline systolic blood pressure (SBP) did not differ between TP(-/-) and TP(+/+), but was significantly lower in the IP(-/-) group than in the IP(+/+). With a high salt diet, SBP in IP(-/-) gradually increased. In contrast, SBP in the IP(+/+), TP(-/-), or TP(+/+) groups remained unchanged. CONCLUSIONS: The prostacyclin receptor may participate in the maintenance of baseline BP. With salt loading, BP adaptation may take place, at least in part, via IP mediated signals.