Motoomi Nakamura

The effects of high oral magnesium supplementation on blood pressure, serum lipids and related variables in apparently healthy Japanese subjects

In a double-blind, placebo-controlled study, thirty-three subjects were allocated to undergo either a 4-week treatment with oral Mg supplementation (Mg(OH)2; 411-548 mg Mg/d) or a placebo. The urinary excretion of Mg increased significantly in both the first 2 weeks and the following 2 weeks of Mg supplementation, while the urinary Na excretion also increased significantly over the experimental period. The systolic and diastolic blood pressure values decreased significantly in the Mg group, but not in the placebo group. The urinary aldosterone excretion and packed cell volume increased significantly during the last 2 weeks of the experimental period compared with the run-in period and first 2 weeks of supplementation. There was a statistically significant positive correlation between the values for urinary noradrenaline excretion and diastolic blood pressure at the end of the supplementation period (both expressed as a percentage of the run-in value). Statistically significant increases in lecithin-cholesterol acyltransferase (EC 2.3.1.43; LCAT), HDL-cholesterol and apolipoprotein AI were also observed after Mg supplementation. A significant positive correlation was observed between the levels of LCAT and urinary Mg excretion for the experimental period (expressed as a percentage of the run-in value). The total cholesterol:HDL-cholesterol ratio decreased significantly during the last 2 weeks of Mg supplementation compared with the first 2 weeks and the run-in periods, but this did not occur in the placebo group. These results suggest that Mg supplementation may lower blood pressure through the suppression of the adrenergic activity and possible natriuresis, while also improving the serum lipids through the activation of LCAT in human subjects.

Association between beta 3-adrenergic receptor polymorphism and a lower reduction in the ratio of visceral fat to subcutaneous fat area during weight loss in Japanese obese women

We investigated whether amino acid substitution of tryptophan by arginine at the residue 64 (64 Arg) of beta 3-adrenergic receptor affects on the degree of reduction in the abdominal fat distribution during a 3-month weight reduction program in either pre- or postmenopausal Japanese women. Beta 3-adrenergic receptor gene polymorphism was examined in 90 Japanese obese women by restriction-enzyme cleavage conformation. The visceral and subcutaneous fat area was measured by magnetic resonance imaging. The baseline body mass index, body weight, fat mass and abdominal subcutaneous and total fat area in 15 obese postmenopausal women with a beta 3-adrenergic receptor (64 Arg) were significantly higher than those in 25 postmenopausal obese women with a beta 3-adrenergic receptor (64 Trp/64 Trp). In contrast, no such differences were found in the 50 premenopausal obese women. After a 3-month weight reduction period, the ratio of visceral to subcutaneous fat areas tended to be lower in both pre-and post-menopausal women with a beta 3-adrenergic receptor (64 Arg), but statistically significant in only the premenopausal obese women (p<0.05). The absolute changes in visceral fat areas in 5 homozygotes with a beta 3-adrenegic receptor (64 Arg/64 Arg) was significantly smaller than those in 50 obese women with a beta 3-adrenegic receptor (64 Trp/64 Trp). These results thus suggest that an amino acid substitution at residue 64 of beta 3-adrenergic receptor may play an important role in the regulation of fat distribution in Japanese obese women.

Aortic medial necrosis with or without thrombosis in rabbits treated with Russell's viper venom and angiotensin II

The aim of the present study is primarily to re-examine an animal model of acute myocardial infarction (AMI) and arterial thrombosis, developed by Constantinides and his colleagues in the 1960s, in both heritable hyperlipidemic rabbits and normal rabbits because they did not study these rabbits. The groups in this study consisted of 29 normal rabbits and 29 Watanabe heritable hyperlipidemic (WHHL) rabbits. These rabbits were administered Russells viper venom (RVV) as a procoagulant, intraperitoneally with serotonin or angiotensin II or saline, intravenously. As a control, 10 normal and 17 WHHL rabbits were administered intravenously with either angiotensin II or saline. These treatments were given on 2 successive days. AMI lesion was found in 8 of 29 normal and 7 of 29 WHHL rabbits receiving RVV and angiotensin or serotonin. Angiotensin II promoted the incidence of aortic thrombosis associated with segmental medial necrosis and an intimal disruption in WHHL rabbits receiving RVV. In the normal rabbits, angiotensin II in addition to RVV induced segmental medial necrosis of the aorta, but angiotensin II alone did not. Thus, we postulated that a synergistic effect of RVV as a cytotoxic substance and a sudden increase in the aortic wall tension by angiotensin II might thus result in acute aortic medial necrosis. The conclusion was that no close correlation between coronary arteriosclerosis and AMI was found in this animal model. The intravenous administration of angiotensin promoted aortic medial necrosis even in normal rabbits treated with RVV and then accelerated aortic thrombosis in the WHHL rabbits treated with RVV.

Sudden pressure elevation can trigger acute muscle cell death of the heart and aorta

The object of this study was to clarify whether or not the acute muscle cell death of the aortic media observed in normal rabbits treated with Russells viper venom (RVV) and angiotensin II (Ang) is a result of either acute hypertension or the apoptotic effect of angiotensin II. The incidence and mean % area necrosis of the aorta and left ventricle in the rabbits receiving RVV and Ang (group 1) were compared with those in rabbits receiving Ang and saline (group 2), RVV and saline (group 3), RVV, Ang type 1 receptor blocker (CV 11974) and Ang (group 4), RVV, Ang and nicardipine, dihydropyridine derivative (group 5) and RVV, Ang type 2 receptor blocker (PD 123319) and Ang (group 6). The incidence as well as the mean % area of acute muscle necrosis of the aortic media and left ventricle in groups 3, 4 and 5 were found to be significantly lower than those in either group 1 or group 6. The mean % area of acute spotty myocardial necrosis in group 2 (Ang, saline) was also significantly higher than that in groups 3, 4 and 5. There was no evidence of cells with positive in situ nick end labeling (TUNEL reaction). As a result, the acute muscle necrosis of the aortic media and left ventricle was considered to be due to the sudden elevation in the blood pressure, but not due to apoptosis mediated through Ang type 2 receptor. We thus conclude that a sudden increase in blood pressure may be one of the triggering mechanisms for an acute onset of cardiovascular disorders.

Oral administration of NO synthase inhibitor failed to promote arteriosclerotic lesions in the aorta and the coronary arteries of rabbits fed cholesterol

We examined whether or not the oral administration of L-nitroarginine methylester (L-NAME), an inhibitor of nitric oxide (NO) synthase, promotes cholesterol-induced arteriosclerosis in the aorta and the coronary artery. Thirty-six male Japanese white rabbits were fed 0.5% cholesterol-containing laboratory chow and randomly assigned to the following three groups: (1) water, (2) 80 microg/ml L-NAME and (3) 400 microg/ml L-NAME in drinking water. The rabbits were fed a 0.5% cholesterol-containing diet for 8 months. During the 8-month period, the concentration of total cholesterol and L-nitroarginine in the serum and the mean blood pressure were measured. The concentration of NO3 in the serum was also measured. After sacrifice, the aortic surface involvement (AI%), the ratio of the thickened intima to the media and the contents of the total cholesterol of the aorta, the maximum % stenosis of the subepicardial large coronary artery, the % frequency of the nearly completely occlusive distal small coronary artery and the area of the myocardial fibrosis were all measured. We found no statistical difference among the three groups regarding the degree of arteriosclerotic lesions of the aorta and of the large coronary artery, and the area of myocardial fibrosis, as well as the serum cholesterol exposure index (the area under the curve of the serum total cholesterol concentration) and the mean blood pressure. However, the serum concentration of L-nitroarginine was approximately 50 and 200 microM/l in groups 2 and 3, respectively. The concentration of NO3 in the serum in group 1 was significantly higher than that in groups 2 and 3. We thus conclude, that the oral administration of L-NAME in the rabbits fed a cholesterol-containing diet for 8 months failed to promote arteriosclerotic lesions in the aorta and the coronary artery, even though the serum concentration of L-nitroarginine increased sufficiently to inhibit NO synthase in the arterial endothelium and the NO3 concentration in the serum decreased in the rabbits given L-NAME.

Causal relationship between occlusive lesions of the coronary artery and myocardial fibrosis in arteriosclerotic rabbits--differences between cholesterol-fed and heritable hyperlipidemic rabbits.

To investigate the causal relationship between lesions of either the proximal large or the distal small coronary arteries and myocardial fibrosis, the hearts and the aortas of 99 cholesterol-fed rabbits with either intermittent or continuous hyperlipidemia for 8 months or more, 44 Watanabe-heritable hyperlipidemic (WHHL) rabbits and 20 normal rabbits were studied histologically. The size and location of the myocardial fibrosis correlated closely with the almost completely occlusive distal small coronary artery which mainly consisted of macrophages, necrosis and calcification but did not correlate with the maximum % stenosis of the large proximal subepicardial coronary arteries in the cholesterol-fed-rabbits. Myocardial fibrosis and almost completely occlusive lesions of the distal small coronary arteries were very rare in the WHHL rabbits, and the maximum % stenosis of the proximal coronary artery and aortic lesions in the WHHL rabbits tended to be greater than those in the cholesterol-fed rabbits. Thus, we are still not certain as to whether or not, the organic stenosis of the subepicardial coronary artery is responsible for myocardial fibrosis in WHHL-rabbits. In conclusion, a causal relationship was observed between myocardial fibrosis and the occlusive lesions of the distal small coronary arteries in cholesterol-fed rabbits, while the arteriosclerotic lesions of the small coronary artery in cholesterol-fed rabbits completely differed from those observed in WHHL-rabbit.

Relationship between nutrient factors and osteo-sono assessment index in calcaneus of young Japanese women

The aim of our study was to investigate the association between nutrient factors and the osteo-sono assessment index (OSI) for calcaneus of young Japanese women. The subjects consisted of 965 young women aged from 18 to 22 years studying at the Department of Food and Nutrition at Nakamura-Gakuen University. The OSI was measured by ultrasonic bone absorptiometry. We found that age, weight, height, exercise, as well as the daily intakes of calcium, phosphorus, protein, energy and sodium were the main factors related to OSI in young women. Positive associations were observed between the OSI and the weight, exercise and daily intakes of calcium, protein and energy, whereas while negative associations were seen between the OSI and the age, height and daily intakes of phosphorus and sodium. In addition, all of these factors were also independently related to the OSI.

RELATIONSHIP BETWEEN SERUM TOTAL CHOLESTEROL LEVEL AND NUTRITIONAL STATUS IN JAPANESE YOUNG FEMALE.

Abstract The serum cholesterol level at a young age is considered to be a significant factor in the high prevalence of coronary heart disease. Seven hundred and ninety-six females, mean age 18.9 (18∼22), participated in both blood sampling and a nutritional survey. The nutritional survey was carried out in 1995 by the 24-hour recall method to determine the individual food consumption. The BMI, serum total cholesterol, HDL-cholesterol and triglyceride were 20.8 (SE 0.08) kg/m 2 , 181 (SE 1.0) mg/dL, 60 (SE 0.4) mg/dL, 66 (SE 1.2) mg/dL, respectively. Higher than normal levels of total cholesterol (>200 mg/dL) and Lp(a) (>30mg/dL) were obtained in 22.1% and 19.3% of the subjects, respectively. The total energy intake was 1700 kcal/day, twenty-seven % of which was derived from fat and 46% from cereals. In a multiple regression analysis, the serum total cholesterol and LDL-cholesterol were found to be significantly associated with the BMI as well as the simple carbohydrate and fat energy ratio, respectively, whereas the HDL showed a significantly negative correlation with the BMI. The triglyceride level was associated with the BMI. These results suggests that the BMI, fat energy ratio and simple carbohydrate intake, such as cakes and beverages, appear to be the main factors influencing of hyperlipidemia in young Japanese females.

Magnesium deficiency in adult rats promotes the induction of ventricular tachycardia by the administration of epinephrine

SummaryThe effects of magnesium deficiency on epinephrine-induced ventricular tachyarrhythmia were investigated in adult rats. Forty-two adult Wistar rats were fed a magnesium-deficient diet while 30 rats were fed a standard diet for 20 days. The plasma magnesium concentration was lower in the magnesium-deficient rats (0.22 ± 0.01mmol/l) than in the control rats (0.76 ± 0.03 mmol/l,P < 0.001). Using a telemetry system, electrocardiograms and arterial blood pressure were recorded on a polygraph in an unrestrained condition. Epinephrine was infused intravenously starting at 5 µg/kg per minute. The QT interval was prolonged to 50 ± 1ms in the magnesium-deficient rats compared with 44 ± 1 ms in the control rats (P < 0.001). Before the administration of epinephrine, no ventricular tachyarrhythmias or seizures were found in either the control or the magnesium-deficient rats. The incidence of epinephrine-induced sustained ventricular tachycardia (VT) was higher in the magnesiumdeficient rats (86%) than in the control rats (43%,P < 0.01). However, this VT did not result in sudden death. Seizures always preceded death in both the magnesium-deficient and control rats while the arrhythmias observed immediately before death were mainly bradyarrhythmias. The present study in an adult rat magnesium-deficient model revealed that magnesium deficiency enhances the susceptibility to epinephrine-induced ventricular tachyarrhythmias.

Cardiac Arrhythmias in Magnesium Deficiency

To clarify malignant arrhythmias in magnesium (Mg) deficiency, we used weanling rats in study 1 and an adult rats in study 2. In study 1, weanling rats were fed either an Mg-deficient diet or a control diet for approximately 2 weeks and then electroencephalogram (EEG) and electrocardiogram (ECG) were recorded during auditory stimulation until death. EEG changes were abrupt attenuation of EEG background activity at the onset of tonic convulsion and then spike-wave complex at the falling down stage in association with marked bradyarrhythmias. When flattening of EEG became after generalized seizures, death occurred within a few minutes but consistent ventricular tachyarrhythmias were not observed. NMDA receptor blockers given intraperitoneally prevented significantly seizure occurrence and sudden death. These results may suggest that sudden death in weanling Mg-deficient rats results from a neurologic trigger.