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Biomedical subjects

Susumu Sasaki

Publications and source records attributed to Susumu Sasaki.

At least 19 recordsLinked to original sources
PubMed2006

[Microvascular decompression for refractory neurogenic hypertension: case report].

It is noted that the increased central sympathetic nerve activity caused by neurovascular compression at the rostral ventrolateral medulla (RVLM) is closely related to the genesis of neurogenic hypertension. The authors present the case of a 49-year-old female with refractory neurogenic hypertension to be uncontrolled even with all kinds of oral antihypertensive medications. After approval by the Ethical Committee in a hospital, she had received an intravenous introduction of calcium antagonist and beta-blocker at home for three years. The subsequent examination detail showed increased sympathetic nerve activity and compression of the left vertebral artery (VA) at the left RVLM on magnetic resonance imaging, and therefore microvascular decompression (MVD) underwent through a left lateral suboccipital approach. The left VA was seen indenting the left RVLM. To ensure the complete decompression, the distal part of VA was moved away from RVLM to fix to the dura of the petrous bone with a glue. Her blood pressure became normalized afterwards without drugs and remained normotensive for 23 months after MVD. In order to decide the surgical indication for pure neurogenic hypertension due to neurovascular compression, a strict differential diagnosis is necessary.

Decompression, Surgical↗
PubMed2005

Severe hyperparathyroidism with bone abnormalities and metastatic calcification in rats with adenine-induced uraemia.

BACKGROUND: Marked parathyroid hyperplasia with bone diseases and vascular calcification are unsolved issues in dialysis patients. In this study, we made azotemic model rats by adenine feeding and analyzed the development and progression of the abnormalities. METHODS: Renal failure was induced in 8-week-old male Wistar rats by feeding 0.75% adenine-containing diet for 6 weeks. Serum parameters, parathyroid hyperplasia, bone changes and metastatic calcification were examined at 2, 4 and 6 weeks. RESULTS: Progressive increase of serum creatinine and inorganic phosphate, and decreased levels of serum calcium and 1,25(OH)2D3 were confirmed. Markedly enlarged parathyroid glands and extremely high PTH levels were observed in all adenine-fed rats compared with the control (PTH: 199.3+/-58.0 vs 10.5+/-3.0 pmol/l, P<0.01, respectively, at 6 weeks). In cortical bone of the femur, the morphometric parameters showed increased bone resorption with increased fibrosis, whereas in the trabecular bone, bone resorption decreased and bone volume increased with a larger amount of osteoid compared with the control. Metastatic calcification in aorta, coronary artery and other soft tissues were also found in adenine-fed rats. CONCLUSIONS: Uraemic rats made by adenine diet developed severe abnormalities of calcium metabolism in a relatively short period and therefore they may serve as a useful model for the analysis of parathyroid hyperplasia and vascular calcification in chronic renal failure.

Adenine↗
PubMed2005

Efficacy of biventricular pacing for dialysis-related hypotension due to idiopathic dilated cardiomyopathy.

A 45-year-old man who had been undergoing maintenance hemodialysis for end-stage renal failure, caused by chronic glomerulonephritis 4 years before, was admitted to our hospital for biventricular pacemaker implantation (BVP). Ten years ago, he was diagnosed with idiopathic dilated cardiomyopathy, and had been suffering from dialysis-related hypotension (DRH) due to low cardiac function over the past year. An electrocardiogram revealed complete left bundle branch block with a QRS duration of 180 ms, and echocardiography showed moderate hypokinesis of the left ventricular wall and systolic asynchronized motion of the septum and free wall. After BVP, the left ventricular ejection fraction had increased from 29% to 40%, and the transmitral rapid left ventricular filling (E wave) and atrial contraction (A wave) ratio (E/A) had improved from 1.3 to 1.0. Before and after BVP, we measured hemodynamic parameters during hemodialysis by successive echocardiography. Before BVP, systemic vascular resistance had decreased, cardiac output had not changed, and hypotension was noted. In contrast, after BVP, cardiac output had increased and systemic vascular resistance had not changed, which caused an increase in blood pressure. We conclude that BVP improved the cardiac function which resulted in an improvement in dialysis-related hypotension (DRH).

Blood Pressure Determination↗
PubMed2005

Low frequency regular exercise improves flow-mediated dilatation of subjects with mild hypertension.

Although exercise is recommended for the primary prevention of hypertension, and although it is generally known to have a beneficial effect on endothelial function, working individuals often find it difficult to maintain a consistent exercise regimen. In the present study, therefore, we examined the effects of infrequently performed exercise on flow-mediated dilatation (FMD), which is an index of endothelial function, in 15 subjects with hypertension (mild hypertensives) and 10 normotensive subjects (normotensives). All subjects performed mild bicycle exercise twice a week for 12 weeks. To assess the FMD, the diameter of the brachial artery was measured using ultrasound at baseline, during reactive hyperemia, and following sublingual administration of nitroglycerin. Measurement of these parameters was performed twice, at the beginning and the end of the exercise program. At the baseline, FMD was significantly lower in the mild hypertensives than in the normotensives. Nitroglycerin-mediated dilatation (NTG-D) was similar in the two groups. The exercise decreased blood pressure in the mild hypertensives, and increased high-density lipoprotein (HDL) cholesterol in both groups. The exercise improved FMD without altering NTG-D in the mild hypertensives, but did not result in any change in the normotensives. Multiple regression analysis revealed that the elevation in FMD was positively associated with changes in HDL cholesterol, and negatively associated with changes in plasma norepinephrine and systolic blood pressure. These findings suggest that regular exercise at a low frequency improves FMD, and thereby endothelial function, and lowers blood pressure in mild hypertensives.

Adult↗
PubMed2005

Augmentation of pulse wave velocity precedes vascular structural changes of the aorta in rats treated with N(omega)-nitro-L-arginine methyl ester.

We examined the relationship between structural changes of the aorta and pulse wave velocity (PWV), and the effects of antihypertensive treatments on PWV in N(omega)-nitro-L-arginine methyl ester (L-NAME)-treated rats. Twelve-week-old Wistar-Kyoto (WKY) rats were divided into the following groups, all of which received drug treatment in their drinking water: an untreated control group (n = 36), an L-NAME-treated group (0.7 mg/ml) (n = 32), an L-NAME and angiotensin converting enzyme (ACE) inhibitor (ACEI)-treated group (imidapril: 0.4 mg/ml) (n = 8), and an L-NAME and hydralazine-treated group (0.2 mg/ml) (n = 10). PWV was measured at the same blood pressure (BP) level as in the control group and the wall-to-lumen ratio of the thoracic aorta was evaluated in all groups. In the L-NAME group, PWV increased compared with the value in the control group, at the same time that BP was increasing. After the third day of treatment, PWV was higher in the L-NAME group than in the control group after adjusting BP to the control level, while the wall-to-lumen ratios were equal between the two groups. After the first week of treatment, not only the adjusted PWV, but also the wall-to-lumen ratios were greater in the L-NAME group than in the control group. With administration of antihypertensive agents, both PWV and the thickening of the aortic wall were reduced, but there was no significant difference between the ACEI and hydralazine-treated groups. In conclusion, in a rat model of nitric oxide (NO) synthesis inhibition, the increase in PWV preceded the vascular structural changes, while antihypertensive treatment reduced both changes. There was no significant difference between treatments with ACEI and hydralazine in this model.

Animals↗
PubMed2004

HMG-CoA reductase inhibitors up-regulate anti-aging klotho mRNA via RhoA inactivation in IMCD3 cells.

OBJECTIVE: Klotho is thought to play a critical role in the development of age-related disorders including arteriosclerosis. Statins may exert vascular protective effects, independent of the lowering of plasma cholesterol levels. We investigated the impact of statins on mRNA expression of the age-suppressor gene, klotho in mIMCD3 cells. METHODS AND RESULTS: Klotho mRNA levels were evaluated with real-time RT-PCR. Atorvastatin and pitavastatin increased the expression of klotho mRNA in a dose-dependent manner. This stimulatory effect was abolished by the addition of mevalonate, GGPP and FPP, essential molecules for isoprenylation of the small GTPase Rho. As was the case with the statin treatment, inhibition of Rho-kinase by Y27632 up-regulated klotho mRNA. In contrast to the statin treatment, stimulation with angiotensin II down-regulated klotho mRNA expression without obvious morphological changes. Furthermore, pretreatment with atorvastatin blunted the angiotensin II-induced response and ameliorated the decrease in klotho mRNA expression towards basal levels. RhoA activity was further evaluated by detection of its translocation. Angiotensin II activated RhoA, whereas statins potently inactivated RhoA and blocked RhoA activation by angiotensin II. CONCLUSION: Statins inactivate the RhoA pathway, resulting in over-expression of klotho mRNA, which may contribute to the novel pleiotropic effects of statins towards vascular protection.

Amides↗
PubMed2004

Effects of angiotensin II type 1 receptor antagonist on pressor responses to pulsatile compression of the rostral ventrolateral medulla in rats.

The rostral ventrolateral medulla (RVLM) is known to be a major center regulating sympathetic and cardiovascular activities. A possible association between neurovascular compression of the RVLM and essential hypertension has been indicated. The present study was performed to determine the role of angiotensin II (AngII) in the pressor and sympathetic responses to pulsatile compression of the RVLM. To determine the role of glutamate and AngII in the RVLM, L-glutamate (Glu) 2 nmol or AngII 100 pmol was injected into the RVLM with or without RVLM pretreatment of kynurenate (Glu receptor antagonist) 3nmol, candesartan (AngII type 1 (AT1) receptor antagonist) 2 nmol, or PD123319 (AngII type 2 (AT2) receptor antagonist) 1 nmol in anesthetized Wistar rats. In addition, to determine the role of glutamate and AngII in the pressor and sympathetic effects to the RVLM compression, kynurenate, candesartan, or PD123319 was locally injected before pulsatile compression of the RVLM. Finally, to determine the effects of peripherally administered AngII antagonists in these pressor and sympathetic excitatory responses, candesartan 0.25 micromol or PD123319 0.05 micromol was intravenously injected before pulsatile compression of the RVLM. Glu injected into the RVLM significantly increased mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (SNA), and these effects were reduced by RVLM pretreatment with kynurenate, but were unaffected by candesartan or PD123319. AngII injected into the RVLM and pulsatile compression of the RVLM also increased MAP and SNA. However, in contrast with Glu injections, these effects were reduced by RVLM pretreatment with candesartan or kynurenate, but were unaffected by PD123319. Pressor and sympathetic excitatory responses to RVLM compression were reduced by intravenous pretreatment with candesartan but not with PD123319. These results indicate that, upon pulsatile compression of the RVLM, AngII may activate RVLM neurons via AT1 receptors and stimulate Glu release to thereby elicit sympathetic activation and pressor effects. Candesartan may exert its hypotensive effect at least in part by affecting the RVLM neurons to reduce sympathetic outflow induced by pulsatile compression of the RVLM.

Angiotensin II↗
PubMed2004

[Case of non-Hodgkin lymphoma with acute renal failure successfully treated with chemotherapy].

We report a case of non-Hodgkin lymphoma (NHL) with acute renal failure. A 62-year-old man was admitted to our hospital on March 8, 2002 with leg edema and dyspnea on effort. About 3 weeks before admission, he was found to have slightly high serum creatinine (Cr) and high lactate dehydrogenase (LDH) levels by another home doctor. Physical examination revealed anemic conjunctivae and leg edema, but the urinary volume was preserved. Blood examination showed high BUN (64 mg/dl) and Cr levels (3.91 mg/dl). Urinary analysis showed proteinuria (1.05 g/day) and high BMG (14,434/microg/day) and NAG (4.55 U/day) levels, suggesting severe tubulointerstitial injury. On ultrasonography of the kidney, the bilateral kidneys showed marked swelling without hydronephrosis. To investigate the genesis of renal failure, we performed a renal biopsy. The specimen showed normal glomeruli, but a large number of cells infiltrated in the tubulointerstitial area with normal tubulointerstitial structure. The cells stained positively with anti-leukocyte antigen and L26 (B cell marker), and negatively with cytokeratin and UCHL-1 (T cell marker). These findings indicate that the interstitial cells were non-Hodgkin lymphoma with B cell diffuse large cells. Chemotherapy was performed with VAD (vincristine sulfate, doxorubicin hydrochloride, dexamethasone) considering his renal dysfunction. To avoid tumor lysis syndrome after chemotherapy, hemodialysis was performed on days 1-4 after the initiation of chemotherapy. After a series of chemotherapy, the urinary volume increased and serum Cr levels decreased to 2 mg/dl. After additional therapy with 4 courses of CHOP, he improved and was discharged on day 180 after admission.

Acute Kidney Injury↗
PubMed2003

HMG-CoA reductase inhibitor enhances inducible nitric oxide synthase expression in rat vascular smooth muscle cells; involvement of the Rho/Rho kinase pathway.

Little is known about the mechanism by which HMG-CoA reductase inhibitors affect inducible nitric oxide synthase (iNOS) expression. We investigated the effect of HMG-CoA reductase inhibitor cerivastatin on iNOS expression in cultured rat vascular smooth muscle cells (VSMCs). Quiescent VSMCs were incubated with or without various concentrations of drugs as follows: cerivastatin, C3 exoenzyme or Y-27632. Then, pretreated VSMCs were stimulated by a vehicle or interleukin (IL)-1beta (10 ng/ml). Treatment of VSMCs with cerivastatin (10(-7)-10(-5) mol/l), which inhibits isoprenylation of Rho and other small G proteins, significantly increased nitrite/nitrate (NOx) production and upregulated the expression of iNOS mRNA in IL-1beta-stimulated VSMCs. This effect of cerivastatin was abolished by cotreatment with mevalonate (2x10(-4) mol/l) or geranylgeranyl-pyrophosphate (GGPP) (10(-5) mol/l), but not by farnesyl-pyrophosphate (10(-5) mol/l). Furthermore, C3 exoenzyme (50 microg/ml), an inactivator of Rho protein, and Rho kinase inhibitor Y-27632 (10(-5) mol/l) also enhanced NOx production and the expression of iNOS mRNA in IL-1beta-stimulated VSMCs. Immunocytochemical study revealed that cerivastatin, C3 exoenzyme and Y-27632 did not affect the nuclear translocation of nuclear factor-kappaB in IL-1beta-stimulated VSMCs. Our study suggests that cerivastatin stimulates iNOS expression in IL-1beta treated VSMCs by its inhibitory effect on Rho/Rho kinase pathway. In addition, this effect of cerivastatin, by enhancing iNOS expression, may contribute to the prevention of restenosis after percutaneous coronary intervention and protect against atherothrombosis.

Analysis of Variance↗
PubMed2003

[Intravascular ultrasound imaging of the renal artery in patients with renovascular hypertension caused by neurofibromatosis 1].

A 26-year-old woman with neurofibromatosis 1 was admitted to our hospital for investigation of prolonged hypertension after toxemia of pregnancy. Plasma renin activity was elevated. From the renogram, stenosis of right renal artery was suspected and we performed renal arteriography, which revealed proximal right renal artery stenosis. The intravascular ultrasound (IVUS) image showed concentric stenosis with intimal and medial hypertrophy, which was iso-echoic and partly high echoic. Percutaneous transluminal renal angioplasty was performed and the lesion was well dilated. After angioplasty, blood pressure normalized in a week. From the clinical course and the IVUS image, we suspected that renal artery stenosis was due to neurofibromatosis 1.

Adult↗
PubMed2002

Effects of atorvastatin on oxidized low-density lipoprotein, low-density lipoprotein subfraction distribution, and remnant lipoprotein in patients with mixed hyperlipoproteinemia.

Atorvastatin (10 to 20 mg/day) was administered for 3 months to 15 outpatients (average age 58 +/- 4 years) with hypercholesterolemia accompanied by hypertriglyceridemia without hypolipemic treatment. Changes in lipid profile, particularly oxidized low-density lipoprotein (LDL) (malondialdehyde LDL), subfractions of LDL, and remnant lipoprotein (RLP) cholesterol, were examined before and after administration. In addition, the influence of atorvastatin on lipoprotein(a) (known to be an independent risk factor for atherosclerosis), asymmetric dimethylarginine (known to be an endogenous inhibitor of nitric oxide synthase), and homocysteine (methionine metabolite) was also investigated. Administration of atorvastatin significantly decreased serum total cholesterol, LDL cholesterol, and triglycerides. Conversely, a significant increase in high-density lipoprotein cholesterol was shown. In LDL subfractions, large, buoyant LDL fractions were not influenced by treatment with atorvastatin (before administration, 99 +/- 14 mg/dl; after administration, 91 +/- 6 mg/dl, shown as a cholesterol content in each subfraction), but a marked decrease in small, dense LDL fractions (p <0.001) (before administration, 119 +/- 17 mg/dl; after administration, 43 +/- 10 mg/dl) was shown. Moreover, oxidized LDL was significantly decreased (p < 0.01) (before administration, 169 +/- 13 U/L; after administration, 119 +/- 10 U/L) and RLP cholesterol also was significantly decreased (p <0.01) (before administration, 11.9 +/- 2.0 mg/dl; after administration, 6.0 +/- 0.9 mg/dl) with atorvastatin treatment. No significant change was observed in fasting plasma glucose, hemoglobin A1c, lipoprotein(a), asymmetric dimethylarginine, homocysteine, and so on. These data suggest that administration of relatively low doses of atorvastatin to patients with hypercholesterolemia accompanied with hypertriglyceridemia results in a decrease not only in LDL cholesterol and triglycerides, but also in oxidized LDL and RLP cholesterol, with an increase in high-density lipoprotein cholesterol. Furthermore, small, dense LDL decreased with a shift in LDL subfractions to large, buoyant fractions, and these changes are considered to be involved in the inhibition of the onset and progression of atherosclerosis.

Anticholesteremic Agents↗
PubMed2002

Comparative effects of candesartan and enalapril on augmented vasoconstrictive responses to endothelin-1 in coronary vessels of spontaneously hypertensive rats.

BACKGROUND: The aim of this study was to compare the effect of angiotensin type-1 receptor blockade (ARB) on augmented vasoconstrictive response to endothelin-1 (ET-1) in coronary vessels of hypertensive hearts with angiotensin converting enzyme (ACE) inhibitor, candesartan cilexetil (CAN) or enalapril was administered for 3 weeks in spontaneously hypertensive rats (SHR). METHODS: We used SHR (9 to 12 weeks old, n = 18) and Wistar-Kyoto (WKY) rats (n = 6). Systolic blood pressure was measured once a week. Spontaneously hypertensive rats were divided into three groups. Enalapril malate (10 mg/day) or CAN (10 mg/day) was administered orally in each of six SHR in each group receiving treatment for 3 weeks. The control group (n = 6) received no treatment. At the end of this experiment, the hearts were isolated. Isolated hearts mounted on a Langendorff apparatus after weighing were then perfused with modified Krebs-Henseleit buffer at constant pressure (75 mm Hg). The coronary perfusion pressure and coronary flow were measured during perfusion of isolated hearts. Coronary vascular resistance (CVR; mm Hg/mL/min/100 g) was calculated. RESULTS: The ET-1 elicited increases in CVR dose-dependently in both normotensive and hypertensive rat hearts. However, the responses were significantly greater in SHR than in WKY rat. Chronic treatment with enalapril or candesartan inhibited the development of hypertension and cardiac hypertrophy equally in SHR. Augmented vasoconstrictive responses to ET-1 were significantly reduced in treated SHR. There was no difference in these effects between enalapril and candesartan. CONCLUSION: These findings suggest that both ACE inhibitors and ARB can equally inhibit augmented coronary vascular response to ET-1 in hypertensive hearts.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Effects of pravastatin on exercise electrocardiography test performance and cardiovascular mortality and morbidity in patients with hypercholesterolemia: Lipid Intervention Study in Kyoto.

The long-term effects of the 3-hydoxy-3-methyl-glutaryl coenzyme A reductase inhibitor, pravastatin, on exercise electrocardiography (ECG) test performance and cardiovascular mortality and morbidity were compared with those of conventional lipid-lowering drugs in hypercholesterolemic patients with no history of myocardial infarction or stroke. One thousand two hundred and seventeen patients were randomly assigned with mean serum cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol levels of 6.98 +/- 0.91mmol/L, 2.08 +/- 1.87mmol/L, 1.38 +/- 0.44mmol/L, and 5.07 +/- 1.14 mmol/L, respectively, and received either pravastatin at a dose of 10-20mg/day (group P) or one of the conventional lipid-lowering drugs such as fibrates, nicotinic acid, and probucol (group C). The numbers of patients available for analysis in groups P and C were 305 and 278 at year 1, 261 and 216 at year 2, 206 and 184 at year 3, 159 and 122 at year 4, and 103 and 81 at year 5. Over the 3.2 year mean follow-up period, the reduction in serum LDL cholesterol levels was significantly greater (p<0.01) in group P (-24.3%) than in group C (-16.0%). Serum HDL cholesterol levels increased in group P (+11.6%), but decreased in group C (-0.3%) (p<0.01). There were no significant differences in the rate of patients who exhibited ischemic changes to exercise ECG test (ischemic responders) between the 2 groups. Coronary heart diseases (CHD) occurred in 6 patients in group P and 13 in group C; pravastatin significantly reduced CHD risk (reduction rate 0.369; 95% confidence interval 0.140-0.970; p<0.05). No significant differences existed between the treatment groups in terms of the number of strokes (group P, 6; group C, 7) or deaths unrelated to CHD (group P, 3; group C, 2). Although pravastatin did not improve the proportion of ischemic responders on exercise testing, it reduced CHD risk and serum LDL cholesterol levels more significantly than conventional lipid-lowering drugs without adversely affecting the risk of stroke and non-CHD death in hypercholesterolemic patients.

Adult↗
PubMed2002

Lowering of blood pressure improves endothelial dysfunction by increase of nitric oxide production in hypertensive rats.

To investigate the effects of angiotensin converting enzyme inhibitor (ACE-I) and other antihypertensive agents on the nitric oxide (NO) release during hypertension, seven- and fourteen-week-old SHR and deoxycorticosterone acetate (DOCA)-salt rats were treated with hydralazine, manidipine (Ca antagonist) or quinapril (ACE-I) for 3 weeks to lower blood pressure. Systolic blood pressure (SBP) was measured by the tail cuff method once each week. Endothelial cells (ECs) derived from the descending aorta of the treated rats were cultured and NOx levels in culture media were measured with an NO analyzer based on the Griess reaction. In both SHR and DOCA-salt rats, antihypertensive therapy lowered SBP to levels similar to those of control rats. The only exception was quinapril treatment of DOCA-salt rats. Although NOx release by ECs derived from hypertensive rats was improved by antihypertensive therapy, the effect was most pronounced in SHR treated with quinapril. In addition, restoration of NOx release was much more remarkable in younger SHR. NOx release was significantly higher in DOCA-salt rats treated with quinapril than in control rats without reduction of SBP. These results suggest that lowering blood pressure improves release of NO by ECs during hypertension and that the time at which antihypertensive therapy is started is also important to preserve endothelial function. Furthermore, ACE-I is suggested to protect endothelial function by increasing NO production in addition to lowering blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗