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Biomedical subjects

T Ishimitsu

Publications and source records attributed to T Ishimitsu.

At least 37 records · Page 2Linked to original sources
PubMed2000

Urinary excretions of albumin and type IV collagen in normotensive and hypertensive subjects.

Plasma albumin leaks into urine as a result of glomerular hypertension and basement membrane injury, while urinary type IV collagen derives from mesangial matrix and glomerular basement membrane. The purpose of this study was to elucidate the pathophysiological significance of these urinary microproteins as an indicator of cardiovascular organ injuries in hypertension. In health-checkup participants without diabetes, proteinuria, or microhematuria, and who were not being treated for hypertension or any other disease at the time of enrollment, urinary albumin and type IV collagen were measured and their relations to organ injuries and cardiovascular risk factors were evaluated. Of 1,079 subjects (40- to 65-year-old; 256 men and 823 women) enrolled in the study, 120 (11.1%) had untreated hypertension exceeding 140/90 mmHg. Urinary albumin was positively correlated with both age (r=0.16, p<0.001) and systolic blood pressure (r=0.27, p<0.001). Urinary type IV collagen was not only positively correlated with age (r=0.12, p<0.001) and diastolic blood pressure (r=0.14, p<0.001) but also negatively correlated with blood hemoglobin (r=-0.12, p<0.001). Urinary albumin, but not type IV collagen, had a significant relation to electrocardiographic signs of left ventricular hypertrophy (p=0.012) and retinal arteriosclerosis on fundoscopy (p <0.001). Thus both albumin and type IV collagen would seem to have increased in association with age and hypertension in this cohort. It is suggested that urinary albumin is an indicator not only of renal injury, but also possibly of development of cardiac hypertrophy and arteriosclerotic changes. Urinary type IV collagen, on the other hand, may be associated with renal tissue injuries that affect erythrokinetics.

Adult↗
PubMed2000

Calcium antagonist inhibits glomerular cell apoptosis and injuries of L-NAME exacerbated nephrosclerosis in SHR.

Increased apoptosis of glomerular cells, with progression of glomerulosclerosis, overactivity of the renin-angiotensin system and elevation of glomerular pressure, follows chronic nitric oxide synthase (NOS) inhibition in spontaneously hypertensive rats (SHR). To gain insight into the regulation of glomerular cell apoptosis in severe nephrosclerosis, we investigated apoptosis, the expression of proliferative cell nuclear antigen (PCNA) in glomeruli, and glomerular morphometric changes in 20-week-old SHR, SHR treated with NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 80 mg/l in drinking water), and SHR treated with L-NAME and the calcium antagonist, efonidipine (20 mg/kg per day), for 3 weeks. Apoptosis in non-sclerotic glomeruli was quantified by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling. The increase in systolic blood pressure and the severe proteinuria with severe nephrosclerosis induced by chronic NOS inhibition were completely prevented by efonidipine. Furthermore, the glomerular area and capillary tuft area were markedly increased in rats treated with efonidipine compared with both control rats (+30 and +42%, respectively, p<0.01) and rats treated with L-NAME (+35 and +56%, respectively, p<0.01)-treated rats. This calcium antagonist also significantly inhibited the both increases of the glomerular cell apoptosis index (-72%) and the PCNA index (+44%), therefore the alteration between apoptosis and proliferation slightly increased the number of glomerular cells (subcapsular, +22%, p<0.01; juxtamedullary, +2%, not significant). Thus, the calcium antagonist efonidipine seems to play an important role in the regulation of apoptosis and proliferation of glomerular cells and may be effective in preventing nephrosclerosis exacerbated by NOS inhibition.

Animals↗
PubMed1999

Amlodipine, a long-acting calcium channel blocker, attenuates morning blood pressure rise in hypertensive patients.

1. The effects of once-daily calcium channel blockers with different plasma half-lives on diurnal blood pressure changes were examined in hypertensive patients. 2. Patients with essential hypertension, nine men and 13 women aged 61 +/- 2 years, were treated with amlodipine or nitrendipine in a random cross-over design for 12-16 weeks each. The study drugs were given once daily as monotherapy (n = 8) or in combination with other classes of antihypertensive drugs (n = 14). The plasma half-life of amlodipine is as long as 36 h, while that of nitrendipine is 10 h. At the end of each treatment period, 24 h ambulatory blood pressure and pulse rate were monitored. 3. Average office blood pressure was comparably controlled below 140/90 mmHg by either amlodipine or nitrendipine, both in the monotherapy and the combination therapy groups; however, pulse rate was greater in nitrendipine than in amlodipine either in the monotherapy (by 6 b.p.m., P < 0.05) or in the combination therapy (by 5 b.p.m., P < 0.01). 4. In 24 h blood pressure monitoring, morning (05.30-09.00 h) blood pressure was higher in nitrendipine than in amlodipine by 6/4 mmHg in the monotherapy (P < 0.05) and by 7/5 mmHg in the combination therapy (P < 0.03), although the blood pressure in the remainder of the 24 h did not differ between the two treatment periods. In addition, pulse rate in the daytime (09.30-18.00 h) was greater in nitrendipine than in amlodipine by 6 b.p.m. in the monotherapy (P < 0.01) and by 7 b.p.m. in the combination therapy (P < 0.02). 5. These results suggest slow pharmacokinetics of amlodipine provides an advantage in controlling morning blood pressure and mitigating reflex activation of the sympathetic nervous system.

Amlodipine↗
PubMed1999

Hypoxia-induced adrenomedullin production in the kidney.

BACKGROUND: Adrenomedullin (AM) is a newly discovered peptide that has a potent vasorelaxant activity. To investigate its potential roles in hypoxia-induced renal injury, we examined whether AM production in the kidney increased under hypoxic conditions. METHODS: The AM transcript levels in Madin-Darby canine kidney (MDCK) cells, rat vascular smooth muscle cells (VSMCs), and rat mesangial cells were assessed by Northern blot analyses under normoxic and hypoxic conditions. The AM peptide in culture media was measured by radioimmunoassay. The effects of hypoxia on accumulation of cAMP in VSMCs were also examined. The stability of AM transcripts under normoxic and hypoxic conditions was compared in the presence of actinomycin D. The effects of hypoxia on AM promoter activity was assessed by transient transfection assays using the AM promoter subcloned upstream of luciferase gene. RESULTS: The expression of AM transcripts increased significantly in MDCK cells, rat VSMCs, and rat mesangial cells under hypoxic conditions without changes in the stability of AM transcripts; however, the AM promoter activity under hypoxic was not elevated significantly. The accumulation of AM peptide in culture media also increased significantly under hypoxic conditions in MDCK cells (2.2 +/- 0.1 fmol/10(5) cells in normoxia vs. 3.5 +/- 0.3 fmol/10(5) cells in hypoxia, 6 hr after hypoxia induction, P < 0.001), and in rat VSMCs (5.5 +/- 0.3 fmol/10(5) cells in normoxia vs. 7.8 +/- 0.4 fmol/10(5) cells in hypoxia, 8 hr after hypoxia induction, P < 0.01). Under hypoxic conditions, cAMP levels in rat VSMCs increased significantly compared with those under normoxic conditions (13.3 +/- 1.4 pmol/well vs. 4.6 +/- 0.4 pmol/well, P < 0.01). CONCLUSIONS: Renal parenchymal cells as well as renal vessels may produce AM under hypoxic conditions.

Adrenomedullin↗
PubMed1999

Insertion/deletion angiotensin converting enzyme gene polymorphism affects the microvascular structure of the kidney in patients with nondiabetic renal disease.

OBJECTIVE: It has been reported that the deletion allele of the insertion/deletion polymorphism of the angiotensin I converting enzyme gene is associated with increased cardiovascular risk and progressive renal disease, including immunoglobulin A nephropathy. We therefore investigated the relationship between angiotensin converting enzyme polymorphism and intrarenal microvascular structure in 56 patients with nondiabetic renal disease. METHODS AND RESULTS: We determined various cardiovascular hormones of the renin-angiotensin system and angiotensin converting enzyme gene polymorphism in 56 patients with nondiabetic renal diseases who underwent a renal biopsy. The patients were divided into three groups by angiotensin converting enzyme genotype (insertion/insertion, n = 21; insertion/deletion, n = 23; deletion/deletion, n = 12) using polymerase chain reaction methods. The angiotensin converting enzyme insertion/ deletion and deletion/deletion genotypes were associated with a significantly higher interlobular artery wall : lumen ratio than the insertion/insertion genotype (insertion/insertion 0.27 +/- 0.01, insertion/deletion 0.32 +/- 0.01, deletion/deletion 0.33 +/- 0.02; P < 0.05). Afferent arteriolar and tubulo-interstitial injury scores were similar among the three genotypes. Although serum angiotensin converting enzyme activity was higher in the deletion/deletion than in the other two genotypes (insertion/insertion 9.7 +/- 0.7, insertion/deletion 10.7 +/- 0.9, deletion/deletion 14.0 +/- 2.4 IU/I; P < 0.05), other factors of the renin-angiotensin system, including blood pressure and serum creatinine levels, were not different among the three groups. CONCLUSIONS: The angiotensin converting enzyme deletion/deletion genotype may be considered a risk factor for the development of microvascular wall thickening in nondiabetic renal diseases.

Adult↗
PubMed1999

Effects of smoking cessation on blood pressure and heart rate variability in habitual smokers.

We investigated the effects of 1-week of smoking cessation on ambulatory blood pressure, heart rate, and heart rate variability in 39 normotensive male habitual smokers (mean+/-SEM, 32.5+/-1.0 years). The ambulatory blood pressure, heart rate, and ECG R-R intervals were measured during a 24-hour period with a portable recorder (TM-2425) on the last day of 1-week smoking and nonsmoking periods. The order of the 2 periods was randomized. In the smoking period, the subjects were instructed to smoke cigarettes according to their usual smoking patterns. 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 milliseconds (pNN50) was used as a time-domain measure of heart rate variability. The 24-hour ambulatory blood pressure was significantly lower in the nonsmoking period than in the smoking period, by 3.5+/-1.1 mm Hg systole [P<0. 01] and by 1.9+/-0.7 mm Hg diastole [P<0.05], whereas the nighttime blood pressure did not differ significantly between the 2 periods. The 24-hour heart rate was significantly lower in the nonsmoking period than in the smoking period, by 7.3+/-1.0 beats/min (P<0.0001). The pNN50 and the 24-hour HF component were significantly higher in the nonsmoking period than in the smoking period (P<0.0001 for each). The plasma norepinephrine and epinephrine concentrations were significantly lower in the nonsmoking period than in the smoking period (P<0.05 for each). These results demonstrate the substantial and immediate benefits of smoking cessation on these cardiovascular indices.

Adult↗
PubMed1999

Acute and chronic effects of a hypocaloric diet on 24-hour blood pressure, heart rate and heart-rate variability in mildly-to-moderately obese patients with essential hypertension.

We examined the acute and chronic effects of a nutritionally balanced, moderately hypocaloric diet on 24-hour ambulatory blood pressure, heart rate and heart-rate variability in mildly-to-moderately obese patients with essential hypertension. We enrolled 16 obese patients with essential hypertension [age: 51-76 years, body mass index (BMI): 26-32 kg/m2]. For the initial week, a standard diet of 2,000 kcal/day was given, followed by a 3-week of a hypocaloric diet of 850 kcal/day. In the last period of the standard diet and in the first and the last periods of the hypocaloric diet, each subject's 24-hour ambulatory blood pressure, heart rate and R-R intervals of the electrocardiogram were recorded, and electrolytes and catecholamines in 24-hour urine samples were also measured. A power spectral analysis of the heart-rate variability was performed over a 24-hour period based on the autoregressive method. The subjects lost 3.7+/-0.3 kg (mean +/- s.e.m.) of body weight during the 3-week hypocaloric diet period. The 24-hour blood pressure did not differ between the last period of the standard diet and the first period of the hypocaloric diet; however, it showed a significant reduction after 3 weeks of the hypocaloric diet. The decrease in the 24-hour blood pressure during the study period was 10.5+/-1.5 mm Hg systole and 4.3+/-1.8 mm Hg diastole. In contrast, the 24-hour heart rate was significantly reduced in the first period of the hypocaloric diet, although the body weight and blood pressure did not change, and the rate was maintained even in the last period of the hypocaloric diet. The decrease in the 24-hour heart rate during the study period was 2.8+/-0.9 beats per minute. The hypocaloric diet did not change any autonomic indices obtained from a power spectral analysis of the heart-rate variability. In conclusion, different responses to a hypocaloric diet were observed between the blood pressure and the heart rate in obese hypertensive patients. The changes in power spectral parameters of the heart-rate variability were less apparent than those found with the blood pressure or the heart rate.

Blood Pressure↗
PubMed1999

[Multicenter prospective survey of prognosis of hypertensive elderly outpatient under antihypertensive treatment--morbidity and mortality of cardiovascular diseases and cancer].

Although calcium-channel blockers and angiotensin-I-converting enzyme inhibitors are often used for treatment of hypertension in the elderly in Japan compared to those in the United States and in European countries, there have been few investigations on the prognosis of the elderly receiving these antihypertensive treatments. The Research Group for "Guidelines on the Treatment of Hypertension in the Elderly" collaborated with the Comprehensive Research Projects on Aging and Health group of the Ministry of Health and Welfare of Japan in performing a 3-year survey on the outcome of 700 hypertensive elderly outpatients (> or = 60 years) receiving treatment of antihypertensive drugs. Antihypertensive drugs including dihydropyridine-type calcium channel blockers, beta blockers, angiotensin-I-converting enzyme inhibitors, diltiazem, diuretics and old-type antihypertensives (hydralazine, budralazine, and centrally acting drugs such as clonidine, methyldopa and guanabenz) were administered to 71.3%, 30.4%, 26.2%, 14.0%, 8.6%, and 6.4% of the 642 elderly patients surveyed for three years, at the time of registration, respectively. Morbidity and mortality rates of total cerebro-cardiovascular diseases, stroke, and heart diseases, were 27.6 and 7.81/1,000 patient-years, 15.1 and 3.6/1,000 patient-years, 10.4 and 4.2/1,000 patient-years, respectively. These results were similar or even better than those of megatrials of antihypertensive treatments for elderly patients in Europe and United States. After adjustment for potential confounding factors, multiple logistic analysis revealed that a past history of ischemic heart disease, use of the old-type antihypertensive drugs, male gender, and diastolic high blood pressure were independent risk factors for the morbidity of cerebro-cardiovascular diseases taking the group of non-cerebro-cardiovascular disease as the reference group. We also identified 22 cases of newly occurred malignancies including 7 fatal cases. However, none of the antihypertensives was significantly related to the occurrence of malignancies. These results lead support to the tendencies in the use of antihypertensive drugs in Japan.

Aged↗
PubMed1998

Transcriptional regulation of human adrenomedullin gene in vascular endothelial cells.

Adrenomedullin (AM) is a recently identified vasodilator peptide produced in cardiovascular organs such as the heart, vascular wall, kidney and lung. Because plasma levels of AM are not different between various portions of the cardiovascular system, vascular cells are supposed to be the main source of circulating AM. To elucidate the regulatory mechanism of human AM gene expression, functional elements of 5'-flanking region of AM gene were studied in human aortic endothelial cells (HAEC). Northern blot analysis revealed considerable AM mRNA expression in cultured HAEC, and 2 transcription start sites were recognized at 21 and 25 bp downstream from the TATA box. The 1534 bp 5'-flanking region DNA inserted in the luciferase vector showed significant promoter activity when transfected into HAEC using liposome. Serial deletion of the inserted 5'-flanking region DNA length resulted in reduction in promoter activity by 41% between 110 and 90 bp and further reduction by 42% between 66 and 29 bp. The 19 bp DNA fragment without TATA box had almost no promoter activity. Gel shift assay revealed presence of HAEC nuclear proteins specifically bound to nuclear factor for interleukin-6 expression (NF-IL6) consensus sequence existing from -85 to -93 bp of the AM gene 5'-flanking region and activator protein 2 (AP-2) consensus sequence clustered from -33 to -68 bp. Furthermore, mutation of NF-IL6 consensus sequence in the 5'-flanking region resulted in 42% reduction in the expression of luciferase activity. These findings suggest that NF-IL6 and AP-2 sites in the promoter region are the functional elements in the transcriptional regulation of human AM gene in vascular endothelial cells.

Adrenomedullin↗
PubMed1998

Agenesis of the right lobe of the liver: report of a case.

A case of congenital agenesis of the right lobe of the liver detected in a patient with gastric cancer is reported. The diagnosis of this rare anatomical variant was established by a combination of computed tomography, abdominal angiography, and operative findings. The importance of accurately recognizing this condition is stressed, and the clinical presentation, radiographic appearance, and differential diagnosis are also discussed.

Aged↗
PubMed1998

Blood pressure and other risk factors before the onset of myocardial infarction in hypertensive patients.

To investigate blood pressure (BP) as well as other risk factors before the onset of myocardial infarction in hypertensive patients, we analysed the BP and metabolic variables in 94 hypertensive patients who had been followed up in our out-patient clinic before the first onset (M1 group; n = 42, 69 +/- 1 years, mean +/- s.e.) or the recurrent onset (M2 group; n = 52, 69 +/- 1 years) of myocardial infarction. Ninety-four hypertensive outpatients who had no history of serious cardiovascular diseases (C group) were also recruited for an age- and sex-matched case-control study. The majority of the patients were taking anti-hypertensive drugs (M1: 90%; M2: 98%; C: 90%). The average BP values for 1 year before the onset of myocardial infarction were used for the analysis. The BPs before the onset of myocardial infarction were 147 +/- 2 mm Hg systole and 81 +/- 2 mm Hg diastole in the M1 group, and 141 +/- 2 mm Hg systole and 78 +/- 1 mm Hg diastole in the M2 group, while those of the C group were 146 +/- 1 mm Hg systole and 84 +/- 1 mm Hg diastole. The diastolic BP of the M2 group was significantly lower than that of the C group (P < 0.0001). In patients aged > or =69 years, the diastolic BP of the M1 and M2 groups (M1: 77 +/- 1 mm Hg; M2: 75 +/- 1 mm Hg) were significantly lower than that of the C group (83 +/- 1 mm Hg). The fasting blood glucose of the M1 and M2 groups was higher than that of the C group. The serum HDL cholesterol of the M1 group was lower than that of the other groups. These results suggest that, in addition to glucose and lipid metabolism disorders, low diastolic BP is associated with the onset of myocardial infarction, especially in reinfarction and in elderly hypertensive patients.

Aged↗
PubMed1998

Comparison of 24-hour blood pressure, heart rate, and autonomic nerve activity in hypertensive patients treated with cilnidipine or nifedipine retard.

We compared the effects of cilnidipine and nifedipine retard on 24-h blood pressure (BP), heart rate (HR), and autonomic nerve activity in patients with essential hypertension. Cilnidipine is a novel and unique 1,4-dihydropyridine calcium antagonist that has the L-type and N-type voltage-dependent calcium channel-blocking action. Fourteen hypertensive outpatients (four men and 10 women; aged 64 +/- 2 years, mean +/- SEM) were enrolled in this study. Their ambulatory BP and electrocardiogram were monitored for 24 h at intervals of 30 min with a portable recorder after a 4-week drug-free period, after a 4-week treatment period with cilnidipine (5 or 10 mg once daily), and after a 4-week treatment period with nifedipine retard (10 or 20 mg twice daily). The order of the three periods was randomized. Autonomic nerve activity was evaluated by a power spectral analysis of HR variability, by using the high-frequency (HF) component as an index of parasympathetic nerve activity and the ratio of the low-frequency (LF) component to the HF component (LF/HF) as an index of sympathovagal balance. Cilnidipine and nifedipine retard significantly reduced the 24-h BP of these patients to similar extents (cilnidipine, -11 +/- 3/-6 +/- 1 mm Hg; nifedipine retard, -15 +/- 3/-6 +/- 2 mm Hg). Cilnidipine did not change the 24-h average HR, whereas nifedipine retard significantly increased it (+3.3 +/- 1.4 beats/min; p < 0.05). Nifedipine retard significantly increased the LF/HF ratio in the daytime and the nighttime. Such changes were limited to the daytime in the treatment period with cilnidipine. These results suggest that cilnidipine is effective as a once-daily antihypertensive agent and had less influence on autonomic nervous system and HR than did nifedipine retard.

Autonomic Pathways↗
PubMed1998

Unexplained fever and aortic regurgitation: a rare presentation of Takayasu's aortitis--a case report.

Takayasu's aortitis is rare in male patients. The authors describe the case of a 48-year-old man with a fever of unknown origin, progressive general fatigue, and dyspnea due to aortic regurgitation. A severely thickened aorta was noted during aortic valve replacement. The diagnosis was based on a histologic examination of an operative specimen of the ascending aorta. Takayasu's aortitis should be considered even in male patients with fever of unknown origin and progressive aortic regurgitation.

Aortic Valve↗
PubMed1998

Inhaled nitric oxide in patients with pulmonary hypertension due to valvular heart disease and chronic lung disease.

The objective of this study was to investigate the effects of inhaled nitric oxide (NO) on chronic pulmonary hypertension (PH). Thirty patients with valvular heart diseases (n=8, group A), chronic lung diseases (n=16, group B), primary PH or PH due to collagen disease (n=6, group C) were studied. NO was delivered for 20 min at concentration of 5, 10, and 20 ppm in spontaneous respiration. After inhalation, percentages of systolic pulmonary artery pressure (%SPAP) levels in group A were significantly decreased compared with those for pre-inhalation by 12%, 14%, and 14% at 5, 10 and 20 ppm, respectively (p<0.05). In group B, %SPAP also significantly decreased by 7, 10, and 14% at 5, 10, and 20 ppm, respectively (p<0.05). However, inhaled NO did not significantly affect %SPAP in group C (p=0.4). There was no significant difference in gas exchange in any of the groups. However, 4 out of 8 patients in group A and 10 out of 16 patients in group B showed decreased partial pressure of arterial oxygen in response to inhaled NO. This study demonstrated that inhaled NO is a selective pulmonary vasodilator in decreasing pulmonary artery pressure (PAP); however, the reaction was different in line with the background disease cause of PH. NO inhalation was most effective on patients with moderate PAP. Furthermore, higher concentrations of NO would be risky in some patients with chronic PH.

Administration, Inhalation↗
PubMed1998

Responses of natriuretic peptides to acute and chronic salt loading in normotensive and hypertensive subjects.

Responses of endocrine systems to acute and chronic salt loading were examined in normotensive and hypertensive subjects. In the acute salt load study, isotonic saline (20 ml/kg for 1 h) was intravenously infused in 10 normotensive subjects and 12 patients with essential hypertension. Plasma noradrenaline was suppressed by saline infusion in the normotensive subjects (-19%, p < 0.05), but was not suppressed in the hypertensive patients (-5%, NS). Plasma brain natriuretic peptide concentration was significantly increased in the hypertensive patients (+15%, p<0.05), while it was unchanged in the normotensive subjects. In the chronic salt load study, 9 normotensive subjects and 30 patients with essential hypertension underwent two 7-d periods of 30 and 260 mmol/d sodium intake. On the basis of the blood pressure change, 17 hypertensive patients were classified as salt-resistant and 13 as salt-sensitive. The salt-sensitive hypertensive patients had suppressed plasma renin activity even during low-salt intake. During high salt intake, the plasma noradrenaline concentration failed to decrease in the salt-sensitive hypertensive patients (-6%, NS), whereas it fell significantly in the normotensive subjects (-27%, p < 0.05) and the salt-resistant hypertensive patients (-33%, p < 0.01). The high-salt intake also increased plasma concentrations of brain natriuretic peptide as well as atrial natriuretic peptide in all groups. In the salt-sensitive hypertensive patients, there was a positive correlation between the increase in blood pressure and that in atrial natriuretic peptide (r= 0.84, p< 0.01). These data indicate that brain natriuretic peptide is involved in chronic changes in body fluid volume. In patients with essential hypertension, acute volume expansion also evokes the response of brain natriuretic peptide. Salt-sensitive hypertension seems to be characterized by blunted response of the sympathetic nervous system. In addition, an increase in atrial natriuretic peptide is likely to play an important role in mechanisms counteracting salt-induced elevation of blood pressure.

Adult↗