Biomedical subjects

Toshio Nishikimi

Publications and source records attributed to Toshio Nishikimi.

46 records · Page 3Linked to original sources

PubMed2002

Possible involvement of oxidative stress in hypoxia-induced adrenomedullin secretion in cultured rat cardiomyocytes.

Although hypoxia induces adrenomedullin gene expression in cultured rat cardiac myocytes, it is still unknown whether oxidative stress is involved in the hypoxia-induced adrenomedullin production. We investigated whether oxidative stress might participate in hypoxia-induced adrenomedullin secretion and whether adrenomedullin might have a protective effect on damaged myocytes. Hypoxia increased adrenomedullin secretion and its gene expression in cardiac myocytes, but not in nonmyocytes. Furthermore, oxidative stress (hydrogen peroxide) also increased adrenomedullin secretion from myocytes. N-acetyl-L-cysteine, a free radical scavenger, completely inhibited the stimulation of adrenomedullin secretion by hydrogen peroxide, and this agent reduced the stimulation of adrenomedullin secretion by hypoxia. Lactate dehydrogenase leakage, a marker of cell injury, was significantly increased with the exposure to hydrogen peroxide and adrenomedullin significantly reduced this leakage. These findings suggest that an oxidative stress may be involved, in part, in the increased adrenomedullin secretion from cardiac myocytes under hypoxic condition. Adrenomedullin secreted from myocytes may play a cell protective role in an autocrine manner.

Acetylcysteine↗

PubMed2002

Plasma atrial natriuretic peptide concentration inversely correlates with left atrial collagen volume fraction in patients with atrial fibrillation: plasma ANP as a possible biochemical marker to predict the outcome of the maze procedure.

OBJECTIVES: We hypothesized that the plasma atrial natriuretic peptide (ANP) level reflects atrial degenerative change and may predict the outcome of the maze procedure. BACKGROUND: Although a larger preoperative left atrial dimension and longer duration of atrial fibrillation (AF) have been reported in patients with persistent AF than in those with sinus rhythm (SR), these individual factors were not enough to predict the outcome of the maze procedure. METHODS: Preoperative plasma ANP levels were measured in consecutive 62 patients who underwent the Kosakai's modified maze procedure. Moreover, we performed histological and molecular biological examinations in the resected left atrial tissues. RESULTS: The preoperative plasma ANP was lower in the AF group (n = 13) than it was in the SR group (n = 49) (p < 0.001). Multiple logistic regression analysis revealed that duration of AF and plasma ANP were independently associated with postoperative cardiac rhythm. Among 41 patients with a higher plasma ANP or shorter duration of AF than the median value, SR was restored in 95% of patients. In contrast, in 21 patients with a lower plasma ANP and a longer duration of AF than the median value, SR was restored only in 48% of patients. Histological examination revealed that the collagen volume in the left atrial tissue was higher in AF than it was in SR and inversely correlated with plasma ANP. In addition, the messenger RNA expressions of ANP, collagen type I and type III were lower in AF than they were in SR. CONCLUSIONS: These results suggest that a combination of plasma ANP and/or duration of AF may predict the success rate for the maze operation. Advanced atrial degenerative change may result in a decrease of atrial ANP secretion.

Aged↗

PubMed2002

Effects of alcohol restriction on ambulatory blood pressure, heart rate, and heart rate variability in Japanese men.

We investigated the effects of alcohol restriction on ambulatory blood pressure (BP), heart rate, and heart rate variability in 33 Japanese male volunteers (37 +/- 1 years, mean +/- SE), who were all habitual drinkers. Subjects were told either to keep their usual drinking habits for 3 weeks (usual alcohol period), or to reduce alcohol intake by at least half of their usual drinking amount (reduced alcohol period). The ambulatory BP, heart rate, and electrocardiographic R-R intervals were measured during a 24-h period with a portable recorder on the last day of each period. A power spectral analysis of R-R intervals was performed to obtain the low-frequency (LF) and high-frequency (HF) components. The percentage of differences between adjacent normal R-R intervals >50 msec (pNN50) was also calculated. The amount of ethanol intake was significantly reduced from 70 +/- 5 mL/day in the usual alcohol period to 19 +/- 3 mL/day in the reduced alcohol period (P < .0001). The daytime systolic BP was significantly lower in the reduced alcohol period than in the usual alcohol period by 4 +/- 1 mm Hg (P < .05). The daytime and nighttime heart rate was significantly lower in the reduced alcohol period than in the usual alcohol (P < .001 for each). The pNN50 and the HF component were significantly higher in the reduced alcohol period than in the usual alcohol period (P < .0001 for each). The LF/HF ratio was significantly lower in the reduced period than in the usual period (P < .01). These results demonstrate that 3-week alcohol restriction produced reductions in ambulatory systolic BP, heart rate, and the index of sympathovagal balance, and augmentations of parasympathetic indices of heart rate variability in Japanese male drinkers.

Adult↗

PubMed2002

Source of plasma adrenomedullin in patients with pheochromocytoma.

Controversy exists as to the origin of plasma adrenomedullin (AM). To elucidate the source of plasma AM, we measured two molecular forms of AM, an active form of mature AM (AM-m) and an intermediate inactive form of glycine-extended AM (AM-Gly), by immunoradiometric assay using specific kits in two female patients with pheochromocytoma before and 3 weeks after surgery. We also measured plasma AM-m, AM-Gly, and AM-T (AM-m + AM-Gly) levels, in addition to plasma epinephrine (E) and norepinephrine (NE) levels, in bilateral adrenal veins of one patient. Although plasma E and NE levels decreased markedly after surgery in these patients, changes in plasma AM appeared to be confined to the normal range. There were no obvious differences in plasma AM-T, AM-m, or AM-Gly levels in adrenal veins between healthy tissue and tumor sides. Furthermore, plasma AM-T, AM-m, or AM-Gly levels in adrenal veins were comparable with those in the infrarenal inferior vena cavae (IVC) or the suprarenal IVC. In contrast, plasma E and NE levels increased in the adrenal vein of the healthy side and increased further in the adrenal vein of the tumor side compared with those in the infrarenal IVC. These results suggest that the origin of plasma E and NE is the adrenal gland and that elevated plasma levels of E and NE in pheochromocytoma are due to excessive production of E and NE in the adrenal gland of the tumor side. In contrast, it is suggested that neither plasma AM levels in the adrenal vein of the healthy side nor those of the tumor side contribute to the systemic levels of plasma AM. The present results appear to be consistent with the hypothesis that the source of circulating AM is systemic vasculature.

Adolescent↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed2002

Effects of smoking cessation or alcohol restriction on metabolic and fibrinolytic variables in Japanese men.

We investigated the effects of smoking cessation or alcohol restriction on metabolic and fibrinolytic variables in Japanese men. In the smoking study, 35 male subjects [32+/-1 (S.E.M.) years] who habitually smoked cigarettes (29+/-3 cigarettes/day) were told either to keep their usual smoking habits for 1 week, or to abstain from cigarette smoking, using a randomized crossover design. In the alcohol study, 33 male subjects (37+/-1 years) who habitually drank alcohol (64+/-6 ml of ethanol/day) were told either to keep their usual drinking habits for 3 weeks, or to reduce alcohol intake by at least up to a half of their usual drinking amount, using a randomized crossover design. In each study, venous blood samples were drawn after a 12-h overnight fast on the last day of each period, and metabolic and fibrinolytic variables were measured. One-week smoking cessation significantly increased serum high-density lipoprotein (HDL) cholesterol levels (P<0.05), and significantly decreased serum lipoprotein (a) levels (P<0.01) and plasma plasminogen activator inhibitor-1 levels (P<0.05). In contrast, 3-week alcohol restriction significantly decreased serum HDL cholesterol levels (P<0.05) and plasma tissue plasminogen activator levels (P<0.05). These results suggest that smoking cessation has substantial and immediate benefits on lipid and fibrinolytic variables in habitual smokers, whereas alcohol restriction increases cardiovascular risks, in some respects, in habitual drinkers.

Adult↗

PubMed2002

Effects of the creation of arteriovenous fistula for hemodialysis on cardiac function and natriuretic peptide levels in CRF.

BACKGROUND: Cardiac failure occasionally is caused by the creation of vascular access for hemodialysis. However, the influence of an arteriovenous (AV) fistula on cardiac function has not been fully elucidated. The present study investigated serial changes in cardiac function and hormonal levels after the AV fistula operation. METHODS: Sixteen patients with chronic renal failure underwent echocardiographic studies before and 3, 7, and 14 days after the AV fistula operation. Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations were measured before and 1, 3, 6, 10, and 14 days after the operation. RESULTS: Creation of an AV fistula produced significant elevations in left ventricular (LV) end-diastolic diameter (+4%), fractional shortening (+8%), and cardiac output (CO; +15%). In LV inflow velocities measured by Doppler echocardiography, deceleration time of the early diastolic filling wave shortened (-12%) and the ratio of the peak velocity of early diastolic to atrial filling (E-A ratio) increased (+18%). The difference in duration of LV inflow and pulmonary venous flow at atrial contraction, a marker of LV end-diastolic pressure, significantly shortened day 14 after the operation (-37%). That is, creation of an AV fistula induced LV diastolic dysfunction toward a restrictive filling pattern. Both ANP and BNP levels increased after the operation, and maximal percentages of increase were observed after 10 days (ANP, +48%; BNP, +68%). In the relationship between cardiac function and hormonal response, the increase in CO was associated with elevation of ANP levels (r = 0.61; P = 0.01), but not BNP levels. Conversely, the increase in E-A ratio correlated only with BNP level elevation (r = 0.60; P = 0.01). CONCLUSION: Our observations indicate that creation of an AV fistula has significant effects on cardiac systolic and diastolic performance, and ANP release is induced by volume loading, but BNP release is stimulated by LV diastolic dysfunction.

Adult↗

PubMed2002

Aminoguanidine inhibits mitogen-activated protein kinase and improves cardiac performance and cardiovascular remodeling in failing hearts of salt-sensitive hypertensive rats.

OBJECTIVES: Congestive heart failure (CHF) is associated with inducible nitric oxide synthase (iNOS) expression in the failing human heart, and recently we have also demonstrated that iNOS expression was upregulated in Dahl salt-sensitive hypertensive (DS) rats with cardiac dysfunction and vascular remodeling. Thus, we evaluated whether aminoguanidine (AG), a selective iNOS inhibitor, protects against cardiac dysfunction and vascular remodeling in DS rats receiving a high-salt diet. METHODS: AG (DSHF-AG, 150 mg/kg per day) or vehicle (DSHF-V) were given from left ventricular hypertrophy stage (11 weeks) to CHF stage (18 weeks) for 7 weeks. The left ventricular end-systolic pressure-volume relationship (contractility: E(es)) was measured by conductance catheter. RESULTS: Decreased E(es) in DSHF-V was significantly ameliorated by AG treatment. The iNOS mRNA and protein expression and phospho-p42/p44 extracellular signal-regulated kinase (ERK) activities in the left ventricle were significantly upregulated in DSHF-V compared with control rats, and significantly suppressed in DSHF-AG compared with DSHF-V. DSHF-V showed a significant increase of perivascular fibrosis and myocardial fibrosis, with all these parameters being significantly improved by AG treatment. CONCLUSIONS: We demonstrated that the selective iNOS inhibitor, AG, may be at least a potential therapeutic strategy for treating CHF and cardiovascular remodeling.

Animals↗

PubMed2002

Renoprotective effect of chronic adrenomedullin infusion in Dahl salt-sensitive rats.

The present study was designed to examine whether chronic adrenomedullin infusion has renoprotective effects in hypertensive renal failure and the mechanism by which chronic adrenomedullin infusion exerts its effects. Dahl salt-sensitive rats and Dahl salt-resistant rats were fed a high salt diet starting at 6 weeks of age. Recombinant human adrenomedullin or vehicle was infused for 7 weeks in 11-week-old Dahl salt-sensitive rats. Dahl salt-resistant rat was used as a control. After 7 weeks, untreated Dahl salt-sensitive rats were characterized by decreased kidney function, abnormal morphological findings, increased hormone levels, increased renal tissue angiotensin II levels, and altered mRNA expressions of transforming growth factor beta (TGF-beta) and components of the renin-angiotensin system compared with Dahl salt-resistant rats. Chronic adrenomedullin treatment significantly improved renal function (serum creatinine -87%, creatinine clearance +114%, urinary protein excretion -59%) and histological findings (glomerular injury score -54%) without changing mean arterial pressure compared with untreated Dahl salt-sensitive rats. Interestingly, long-term human adrenomedullin infusion decreased the endogenous rat adrenomedullin level (-97%) with a slight increase of human adrenomedullin level. Chronic adrenomedullin treatment also significantly inhibited the increase of plasma renin concentration (-269%), aldosterone level (-82%), and renal tissue angiotensin II levels (-60%). Furthermore, adrenomedullin infusion significantly decreased the increases of mRNA expressions of TGF-beta (- 63%), angiotensin-converting enzyme (-137%), renin (-230%), and angiotensinogen (-38%) in renal cortex. These results suggest that increased endogenous adrenomedullin plays a compensatory role in chronic hypertensive renal failure and that long-term adrenomedullin infusion has renoprotective effects in this type of hypertension model, partly via inhibition of the circulating and renal renin-angiotensin system.

Adrenomedullin↗

PubMed2002

Long-term adrenomedullin infusion improves survival in malignant hypertensive rats.

Previous studies have demonstrated that adrenomedullin has inhibitory effects on the proliferation and DNA synthesis of mesangial cells and vascular smooth muscle cells in vitro and that plasma adrenomedullin levels are markedly elevated in malignant hypertension. This study was designed to examine whether chronic adrenomedullin infusion has renoprotective effects in malignant hypertensive rats. We studied the following 3 groups: control Wistar Kyoto rats, deoxycorticosterone acetate-salt spontaneously hypertensive rats, and adrenomedullin-treated deoxycorticosterone acetate-salt spontaneously hypertensive rats. Chronic adrenomedullin infusion using an osmotic minipump was started simultaneously with deoxycorticosterone acetate-salt treatment. After 3 weeks of the treatment, malignant hypertensive rats were characterized by higher blood pressure, kidney weight, urinary protein excretion, glomerular injury score, plasma renin concentration, aldosterone level, endogenous rat plasma adrenomedullin level, renal cortical tissue angiotensin II level, angiotensin-converting enzyme mRNA level, and transforming growth factor-beta1 mRNA level in the renal cortex, and by lower creatinine clearance, compared with the control rats. Chronic adrenomedullin infusion significantly improved these parameters (kidney weight -6.5%, urinary protein excretion -63.8%, glomerular injury score -38.3%, plasma renin concentration -52.4%, aldosterone -23.2%, rat adrenomedullin -28.6%, renal angiotensin II -28.1%, renal angiotensin-converting enzyme mRNA -38.3%, renal transforming growth factor-beta1 mRNA -56.2%, and creatinine clearance +20.5%) without significant reduction of mean arterial pressure (-4%). Kaplan-Meier survival analysis showed that adrenomedullin infusion significantly prolonged survival time. These results suggest that subdepressor dose of chronic adrenomedullin infusion has renoprotective effects in this malignant hypertension model, at least in part, via inhibition of the circulating and intrarenal renin-angiotensin system.

Adrenomedullin↗