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Biomedical subjects

H Mikami

Publications and source records attributed to H Mikami.

At least 127 records · Page 7Linked to original sources
PubMed1993

Role of tissue renin angiotensin system in two-kidney, one-clip hypertensive rats.

To investigate the molecular pathology of two-kidney, one-clip (2K-1C) rats, we examined the gene expressions of the renin-angiotensin system (RAS) and angiotensin II (ANG II) concentration in various tissues in the early (4 wk) and chronic (16 wk) phases of hypertension. Four weeks after clipping, the brain renin mRNA level was lower in 2K-1C rats than in control rats (P < 0.05). On the other hand, the levels of brain and renal angiotensinogen mRNA were not significantly different in the two groups. The brain and adrenal ANG II concentrations were significantly higher in 2K-1C rats than in control rats. Sixteen weeks after clipping, there was no significant difference in the brain renin mRNA levels in the two groups, and renal and brain angiotensinogen mRNA levels were normal. Moreover, the ANG II concentrations in the adrenals and brain (except the cortex) of 2K-1C rats were not significantly higher than those in control rats. These results show a differential pattern of tissue RAS gene expression in rats during the development of 2K-1C hypertension, which is regulated in a tissue-specific manner. Furthermore, the data suggest that brain ANG II may be affected by circulating ANG II, but not by the brain renin angiotensin system, and may regulate brain renin, probably by negative feedback through its own receptor.

Actins↗
PubMed1993

Role of angiotensin II in high fructose-induced left ventricular hypertrophy in rats.

Recent studies suggest the linkage of hypertension and insulin resistance. High fructose diet is known to induce hyperinsulinemia and hypertension in rats. In a previous study, however, high fructose (66%) diet failed to elevate blood pressure but increased left ventricular weight in Sprague-Dawley rats. In the present study, we investigated the precise mechanism of high fructose diet-induced changes in the cardiovascular system in rats. Intake of fructose-enriched diet for 2 weeks increased serum insulin and plasma angiotensin II levels. Urinary excretion of sodium and norepinephrine was not changed. Blood pressure measured directly through an indwelling catheter was not increased, but left ventricular weight and protein content were increased by high fructose diet. To further elucidate the role of the renin-angiotensin system, an angiotensin II type 1 receptor antagonist, TCV-116, was given orally at 1 mg/kg per day with either normal or high fructose diet. Concomitant administration of TCV-116 did not affect plasma glucose or serum insulin levels. Plasma angiotensin II was increased, but neither urinary sodium nor norepinephrine was changed by TCV-116. TCV-116 similarly decreased blood pressure in rats on normal and high fructose diets. Increase in left ventricular weight induced by high fructose diet was prevented by the concomitant administration of TCV-116. On the other hand, left ventricular weight in control rats was not changed by TCV-116. In conclusion, increased plasma angiotensin II may account for the left ventricular hypertrophy induced by high fructose diet, whereas hemodynamic change, sodium retention, and the sympathetic nervous system do not play an important role.

Angiotensin II↗
PubMed1993

Angiotensin blockade and the progression of renal damage in the spontaneously hypertensive rat.

The pathophysiological role of angiotensin II in the development of renal sclerosis was investigated in 5/6-nephrectomized, 12-week-old male spontaneously hypertensive rats. After 1 week of a control period, nephrectomized rats received one of the following treatments for 4 weeks: the selective nonpeptide angiotensin II type 1 receptor antagonist TCV-116 (1 mg/kg per day), the angiotensin converting enzyme inhibitor delapril (30 mg/kg per day), hydralazine (15 mg/kg per day), or vehicle. Urinary protein and albumin excretions and systolic blood pressure were determined every week. Rats with reduced renal mass treated with vehicle had a poor survival rate (30%). Although TCV-116, delapril, and hydralazine treatment significantly improved the survival rate for 4 weeks, hydralazine failed to improve proteinuria and albuminuria as well as the decline in renal function compared with delapril or TCV-116. Histological examination revealed that both TCV-116 and delapril protected glomeruli from sclerosis, whereas hydralazine did not improve histological findings (5%, 7%, and 30% of glomeruli were affected, respectively). These results indicate that angiotensin II plays a dominant role through its type 1 receptor in the pathogenesis of renal deterioration by hypertension.

Albuminuria↗
PubMed1993

Hypertensive rats produced by in vivo introduction of the human renin gene.

We established an efficient and nontoxic in vivo gene transfer method mediated by the Sendai virus (hemagglutinating virus of Japan [HVJ]), liposomes, and nuclear protein. In this study, to produce a hypertensive model rat that is dependent on human renin, the human renin gene was introduced into adult rat liver by our efficient in vivo gene transfer method using HVJ and liposomes (HVJ-liposomes). The rats treated with HVJ-liposomes containing the human renin gene showed a significant elevation of blood pressure for 6 days compared with control rats, which received injections of HVJ-liposomes without the human renin gene. On day 5 after the transfer, human active renin as well as angiotensin II were found in the plasma of rats in which the human renin gene was introduced. Moreover, the blood pressure of these rats was significantly correlated with the plasma levels of human active renin and angiotensin II. To confirm that the elevated blood pressure was due to the expression of the human renin gene, we administered a newly developed specific human renin inhibitor, FK 906. The elevated blood pressure was normalized by the intravenous administration of this drug. These data indicate that this hypertensive rat was produced by the in vivo transfer of the human renin gene into rat liver and that the expressed human renin cleaved rat substrate (angiotensinogen). This hypertensive rat produced by in vivo gene transfer should be useful in further studies on hypertension.

Angiotensin II↗
PubMed1993

[Age estimation from tooth attritions of lower incisors--discussion on the "Amano's method"].

As a method of age estimation from teeth we focused our attention on attritions of lower incisors. Using the Amano's method, we took records of tooth attritions in the planted state of 83 subjects whose ages ranged from 14 to 76 years. A positive correlationship was found to exist between the tooth attrition index and the actual age, allowing to establish the following formula which graphically shows a straight line: Y = 8.505X + 26.073 (r = 0.607), where X is the mean of attrition indexes of lower incisors and Y, the estimated age. In our method of age estimation through attrition indexes, we took advantage of probability and confidence interval. In addition, our method was contrasted with Amano's method, a widely used one in Japan.

Adolescent↗
PubMed1993

[Estimation of death time by measurement of circadian melatonin rhythm].

In order to establish a method for the estimation of death time (DT) from measuring melatonin (MT) contents in pineal bodies (PBs) and biological fluids, 85 cadavers were investigated--44 dead in Sapporo (N 43 degrees 4', E 141 degrees 21') and 41 in Tokyo (N 35 degrees 39', E 139 degrees 44'). MT contents were measured by radioimmunoassay in 76 PBs, 27 sera and 14 urines. Exponential differences were recognized between peaks in nighttime and nadirs in daytime of pineal MT contents, i. e., ranging 0.099-63.158 ng per PB and 1.2-609.6 pg/mg. Circadian rhythms were also observed on the concentrations of MT in serum (11-205 pg/ml), and in urine (7.5-137.5 pg/ml). Consequently, criteria of the DT estimation were proposed as follows. 1) Pineal MT contents--(1) 0-0.2 ng/PB:DT 11:00-17:00, (2) 0.2-0.3 ng/PB:DT 7:00-20:00, (3) 0.3-1 ng/PB: incapable of DT estimation, (4) 1-4 ng/PB:DT 16:00-10:00, (5) 4-8 ng/PB:DT 20:00-8:00, (6) 8 ng/PB over: DT 20:00-5:00, 2) Serum MT concentration--(1) 0-100 pg/ml: incapable of DT estimation, (2) 100pg/ml over: DT 22:00-1:00, and 3) Urinary MT concentration--(1) 0-35pg/ml: incapable of DT estimation, (2) 35 g/ml over: DT 18:00-6:00. Furthermore, width of the estimation is able to be narrowed by the combination of these three criteria. The present method is very useful in narrowing the width of DT estimation which has been usually carried out by observing the progress of cadaveric phenomena on and in dead bodies.

Adolescent↗
PubMed1993

Evaluation of orthostatic hypotension using power spectral analysis.

To evaluate the pathogenesis of orthostatic hypotension, we studied the autonomic regulation system by measuring heart rate variability during 60 degrees passive head-up tilt using power spectral analysis in 21 patients with orthostatic hypotension (mean age 62 +/- 2 years, five with histories of cerebrovascular accidents, five with Parkinsonism, five with diabetes mellitus, three with pheochromocytoma, and three with unknown causes) and 15 normal healthy subjects as a control (mean age 63 +/- 2 years). We also assessed plasma epinephrine and norepinephrine response to tilt. During tilt, control subjects showed an increase in heart rate with no change in blood pressure. Spectral analysis of heart rate variability demonstrated increases in the low frequency band (LFB, mainly sympathetic) and low frequency band/high frequency band ratio (LFB/HFB, sympatho-vagal balance). All patients with orthostatic hypotension showed a significant reduction in blood pressure with an increase in heart rate. In patients with histories of cerebrovascular accidents and with Parkinsonism, LFB and the LFB/HFB ratio did not increase. However, in other patients with orthostatic hypotension, LFB and the LFB/HFB ratio increased during tilt. Norepinephrine increased in control subjects and in patients with diabetes mellitus, pheochromocytoma, and unknown causes. In contrast, patients with histories of cerebrovascular accidents and patients with Parkinsonism showed no increase in norepinephrine. Epinephrine responses paralleled those of norepinephrine, but the changes were not significant. Thus, neurological response to tilt is not uniform in patients with orthostatic hypotension. Patients with histories of cerebrovascular accidents and patients with Parkinsonism may have impaired function of central neural mechanisms controlling blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1992

Hypotensive effect associated with a phospholipase C-delta 1 gene mutation in the spontaneously hypertensive rat.

To identify the genes responsible for blood pressure in the spontaneously hypertensive rat strain, we performed a cosegregation analysis between the genotype and blood pressure in a set of male F2 rats obtained by crossmating SHR with Wistar-Kyoto rats, a parental normotensive strain. Our investigation revealed that the phospholipase C-delta 1 polymorphism, which resulted in missense mutation, cosegregates with the lower blood pressure in SHR, and that PLC-delta 1 gene is located on chromosome 8. On the other hand, we found the lack of cosegregation between blood pressure and the nerve growth factor receptor gene, which is linked to a hypertensinogenic gene locus (denoted as BP/SP-1) on chromosome 10. We propose that PLC-delta 1 gene itself of closely linked gene on chromosome 8 is a new candidate with the hypotensive effect, and that BP-SP1 locus does not directly contribute to blood pressure elevation in original SHR.

Animals↗
PubMed1992

Direct in vivo gene introduction into rat kidney.

We established a simple and highly efficient method for in vivo gene transfer using HVJ (Sendai virus) and liposomes. Plasmid DNA and high mobility group 1 (HMG1) protein were co-encapsulated in liposomes by agitation and sonication and were co-introduced into cells by HVJ-mediated membrane fusion. pACT SVT DNA, as a reporter gene, was introduced into the kidney of intact rats through a cannula in the renal artery, and SV40 large T antigen was detected by enzyme immunohistochemistry in glomerular cells 4 days after its introduction. This newly developed kidney-directed gene transfer method should be useful not only in basic research but also in potential gene therapeutics of renal diseases.

Actins↗
PubMed1992

Spectral change in heart rate variability in response to mental arithmetic before and after the beta-adrenoceptor blocker, carteolol.

Spectral analysis of heart rate fluctuation was evaluated before and after administration of carteolol, a non-selective beta-adrenoceptor-blocker, to investigate the neural regulatory mechanisms underlying the haemodynamic changes induced by mental stress. Mental stress increased blood pressure and heart rate, with an increased low frequency band, and low frequency/high frequency ratio of the power spectral analysis which are indices of sympathetic activity. Carteolol did not change basal and pre-mental stress measurements of blood pressure, heart rate and spectral density. However, carteolol altered the response to mental stress with a decrease in spectral density of the low frequency band and low frequency/high frequency ratio, and an increase in the high frequency component. These results confirm that mental stress elevates blood pressure by activating the sympathetic nervous system, and suggest that blockade of the beta-adrenoceptor attenuates the pressor response by preventing the autonomic responses to mental stress.

Blood Pressure↗
PubMed1992

Role of cardiac angiotensin II in isoproterenol-induced left ventricular hypertrophy.

Angiotensin II (Ang II) has been shown to induce proliferation of cardiac myocytes. To examine the role of Ang II in left ventricular (LV) hypertrophy, isoproterenol was infused subcutaneously into 9-week-old male Wistar rats at 4.2 mg/kg/day for 7 days. Infusion of isoproterenol increased LV weight and Ang II concentrations in plasma and in LV tissue. In anephric rats, LV weight and tissue Ang II were increased similarly, but plasma Ang II was not changed by isoproterenol. Concomitant oral administration of trandolapril and isoproterenol prevented increases in both LV Ang II and LV weight. Treatment with hydralazine decreased blood pressure in a similar way as trandolapril but did not affect either LV weight or LV Ang II. Plasma Ang II was not decreased by either trandolapril or hydralazine when administered in combination with isoproterenol. These results suggest that cardiac tissue Ang II regulates myocyte growth in isoproterenol-induced LV hypertrophy, and the reduction of Ang II partly explains the prevention of cardiac hypertrophy by the converting enzyme inhibitor.

Angiotensin II↗
PubMed1992

[Effect of antihypertensive treatment in elderly hypertensive patients with cardiac hypertrophy].

In elderly hypertensive patients effect of antihypertensive treatment with Ca antagonist or ACE inhibitor on the heart were examined. Twenty-four elderly hypertensive patients with cardiac hypertrophy, aged 65-79 years old (mean +/- SEM, 71 +/- 1) were treated with Ca antagonist (nifedipine or nicardipine) or ACE inhibitor (captopril or enalapril) for 3 months. Thirteen patients had essential hypertension (EH: SBP greater than or equal to 160 mmHg and DBP greater than or equal to 95 mmHg, 70 +/- 1 years) and 11 had isolated systolic hypertension (ISH: SBP greater than or equal to 160 mmHg and DBP less than 95 mmHg, 74 +/- 2 years). Blood pressure (BP) and heart rate were measured every two weeks. In all patients, M-mode echocardiography was performed to measure left ventricular mass index (LVMI) and ejection fraction (EF), and the sympathetic nervous (plasma norepinephrine and epinephrine) and the renin-angiotensin system (plasma renin activity and aldosterone concentration), were assessed before and after 3 months of treatment. BP significantly decreased from 174 +/- 3/97 +/- 1 to 149 +/- 4/84 +/- 2 mmHg in EH and from 167 +/- 3/82 +/- 2 to 144 +/- 4/74 +/- 2 mmHg in ISH. LVMI was significantly reduced from 204 +/- 14 to 174 +/- 16 g/m2 in EH and from 179 +/- 14 to 156 +/- 12 g/m2 in ISH. EF showed no significant changes in either group. In ISH, the change in LVMI was significantly correlated with the change in systolic BP (r = 0.74, p less than 0.05). In EH, there was no significant relation between BP and LVMI changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Cushing's syndrome found during long-term glucocorticoid treatment of rheumatoid arthritis in an elderly woman].

A 69-year-old female patient had been treated with glucocorticoid for eight years because of rheumatoid arthritis. She showed characteristic Cushingoid features such as central obesity, moon face, and fragility of skin and vessels. She was disabled because of spinal compression fracture and muscle weakness. The blood pressure was 186/100 mmHg and the laboratory tests revealed serum K: 2.8 mEq/l, WBC: 15, 510/mm3, total cholesterol: 310 mg/dl. These suggested that she had iatrogenic Cushing's syndrome. After discontinuation of glucocorticoid, however, the serum cortisol level remained high. This fact prompted us to conduct further examinations for Cushing's syndrome. Oral dexamethasone administration did not suppress the plasma cortisol level and a left adrenal adenoma was found on abdominal CT scan. Because of the presence of bleeding diathesis, operation for adenoma was contraindicated. Though we tried to treat her with metyrapone, trilostane or opeprim (OP'-DDD), we had to abandon specific treatment because of severe side effects such as acute adrenal dysfunction and gastrointestinal problems. Decrease in the endogenous cortisol level after metyrapone treatment caused exacerbation of symptoms of rheumatoid arthritis. This is a peculiar case in which the long-term administration of glucocorticoid for rheumatoid arthritis might have concealed Cushing's syndrome, and conversely the increased intrinsic adrenal steroid hormone might have suppressed the activity of the rheumatoid arthritis.

Aged↗
PubMed1992

[An elderly case of hypertension with persistent orthostatic hypotension].

The authors report the successful control of labile hypertension associated with orthostatic hypotension in a 75-year-old male patient, by means of L-DOPS, a synthetic precursor of norepinephrine in combination with antihypertensive drugs. He had been known to be hypertensive for 15 years and developed a persistent floating sensation 2 years age. Despite good control of hypertension after admission, orthostatic hypotension was still observed. Passive tilt produced a blood pressure reduction of 60/20 mmHg. Spectral analysis of heart rate variability showed a disturbance in the activation of the sympathetic nervous system. Treatment with L-DOPS attenuated the blood pressure reduction in response to passive tilt (35/12 mmHg) and improved the sympathetic response. Because of an increase in blood pressure by L-DOPS, addition of either a calcium channel blocker or an angiotensin-converting enzyme inhibitor was necessary. These combinations of treatment successfully controlled blood pressure as well as orthostatic hypotension.

Aged↗
PubMed1992

[Dysuria in male elderly outpatients evaluated by a questionnaire survey].

We surveyed complaints of dysuria in male elderly outpatients by questionnaire survey. Seven hundred and twenty outpatients (39 aged 30-39, 63 aged 40-49, 170 aged 50-59, 229 aged 60-69, and 219 aged 70 or more) visiting our outpatient internal medicine clinics were asked by a questionnaire about the subjective symptoms of dysuria, including frequencies of nocturia, prolongation of the start of urination, straining at urination, and residual urine, graded as asymptomatic, mild, moderate and severe. The subjects were divided into three groups as to the dysuria; normal group without symptoms or one mild symptom, borderline group with two or more mild symptoms, and dysuria group with one moderate or severe symptom or more. The rates of the patients in the dysuria group were increased with age, being 15%, 16%, 21%, 31% and 53%, respectively, in the above-mentioned age groups. This finding emphasized the importance of questions about dysuria in elderly patients also in internal medicine outpatient clinics, and of differential diagnosis for the causal factor(s) for dysuria in elderly patients including benign prostate hypertrophy.

Adult↗
PubMed1992

[Drug compliance in the elderly].

In order to clarify the characteristics of elderly patients concerning their attitudes toward taking prescribed medicine, self-reported compliance with prescriptions was compared among different age groups. We performed a survey in 626 outpatients and their attending physicians in 4 of our affiliated hospitals, and analyzed self-reported compliance by the patients to the prescription and their answers to questions related to drug-taking along with the diagnoses and prescriptions reported by the physician. The number of prescribed medicine was 2.3 tablets on the average for patients younger than 40, while 5.1 tablets were prescribed for patients over 70. However, self-reported compliance was best in patients over 70 than in other age groups. Compliance was good in 76% of patients who answered that the amount of medicine was appropriate, while good compliance was lower in those who thought the prescription excessive (67%). Likewise, compliance of patients who had concerns with drug side effects or who were not feeling well under medication was lower than that of patients who felt well under medication. Prescriptions for after lunch were most liable to be forgotten than those for other times of the day. Moreover, a high percentage of elderly patients attended more than 2 departments or medical facilities, and one third of those patients did not inform the physician of the fact suggesting that they were at higher risks of overdosing and unexpected drug interaction. Furthermore, the percentage of patients who did not receive explanation from physicians was higher in the elderly thus demonstrating that elderly patients have quite different characteristics in attitude with regard to medicine from younger age group patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗