Clinical application of the second morning urine method for estimating salt intake in patients with hypertension.

Estimation of salt intake by cumbersome 24-h urine collection is not suitable for individual patients because of substantial daily variation in intake. We developed the second morning urine (SMU) method for monitoring daily salt intake in healthy subjects by calculating the daily creatinine excretion and measuring the ratio of sodium to creatinine in the SMU specimen. To determine whether the SMU method was applicable to hypertensive patients, we tested it in hospitalized patients under an equilibrated sodium balance as a model population. This review focuses on application of the SMU method in hypertensive patients with mild target organ damage.

A long-term, comprehensive exercise program that incorporates a variety of physical activities improved the blood pressure, lipid and glucose metabolism, arterial stiffness, and balance of middle-aged and elderly Japanese.

A 6-month, twice-a-week exercise program emphasizing swimming was conducted for 11 men (57-73 years) and 24 women (51-68 years). The control group comprised 11 male (59-70 years) and 11 female (53-70) volunteers. The exercise program significantly improved the systolic and diastolic blood pressure (SBP/DBP) and lipid and glucose metabolism, with no change in the controls. Brachial-ankle pulse wave velocity (baPWV), as an index of systemic arterial stiffness, was measured during medical examinations before and after each exercise session using a volume-plethysmographic apparatus. SBP and DBP of the extremities were significantly decreased after exercise, but did not change in the controls. Average baPWV decreased significantly in the exercise group, from 1661±50 to 1581±40 cm per sec. No change was seen in the controls. The sway path of the center of balance was analyzed using a force plate. The length of postural sway, the length of postural sway per sec and the area of postural sway were measured with eyes open and eyes closed, and the rectangular area was calculated. The eyes open/eyes closed ratio (Romberg sign) was also calculated. All parameters of body sway were significantly lower after 6 months in the exercise group, with no change in the controls. The Romberg sign did not change for either group. In addition to promoting better health, as shown by the clinical data, this type of exercise program improves balance function, which could help prevent falls of the elderly.

Antihypertensive and natriuretic effects of less-sodium soy sauce containing gamma-aminobutyric acid in spontaneously hypertensive rats.

We investigated the mechanism of the antihypertensive effect of less-sodium soy sauce containing gamma-aminobutyric acid (GABA) in spontaneously hypertensive rats (SHRs). When SHRs were given a diet with less-sodium soy sauce containing GABA (GABA-rich soy sauce group) for 6 weeks, the systolic blood pressure decreased as compared with that in rats fed diets with less-sodium soy sauce or a solution of salt. Renal sympathetic nerve activity (RSNA) and positive Na balance were reduced, and the urinary Na excretion tended to increase in the GABA-rich soy sauce group. Vascular hypertrophy of the thoracic aorta and the coronary and renal interlobular arteries tended to reduce in the GABA-rich soy sauce group. These results suggest that inhibition of Na retention by natriuresis, as a result of inhibition of RSNA by the GABA in the soy sauce contributed to the antihypertensive effect of GABA in the SHRs. Intake of less-sodium soy sauce containing GABA might help to reduce overall cardiovascular risk.

Severe emotional hypertension compatible with 95-year lifespan and little end-organ damage: 24-year record.

We report on an interesting case of longevity in an elderly Japanese woman whose blood pressure (BP) continued extremely high from her first recording at the age of 38 years to her first hospitalization at the age of 81. BP recordings taken by her physician indicated mostly severe or occasionally mild hypertension (HT): between 260/130 and 140/76 mmHg. No antihypertensive drugs were taken during the 25 year span between ages 56 and 80. After her physician died, when she was 80, she changed clinicians and was given several kinds of antihypertensive drugs. She began to feel faintness, dizziness, and severe fatigue. At the time of the first hospitalization, no remarkable cerebral or cardiac abnormalities were observed, despite her BP as high as 210/110 mmHg. BP as measured by nurses or the physician in charge were always above 160/80 mmHg. After discharge, she was asked to measure BP by herself at home. These readings were 140-150/70-80 mmHg on the average, indicating a rare case of long-term emotional blood pressure response. The patient died not of a cerebrocardiovascular accident, but of acute renal failure at 95 years of age. Even though her recorded BP was extremely high when measured by medical staff members and still far above the current conventional desired limit of 120 mmHg systolic (S) BP or the earlier limit of 140 mmHg SBP, it was actually acceptable for her retrospectively, insofar as she lived to age 95. Although antihypertensive drug therapy may be helpful in some cases, it may not be necessary in others. Intensive drug therapy may even be harmful for misdiagnosed emotionally HT patients particularly those misdiagnosed with refractory hypertension, when the response to health care professionals may be emotional.

The prevalence of diabetes mellitus and impaired fasting glucose/glycaemia (IFG) in suburban and rural Nepal-the communities--based cross-sectional study during the democratic movements in 1990.

A rising prevalence of Type 2 diabetes and impaired fasting glucose/glycaemia (IFG) was recently reported in the urban areas of Nepal by Singh and Bhattarai [D.L. Singh, M.D. Bhattarai, High prevalence of diabetes and impaired fasting glycaemia in urban Nepal, Diabet. Med. 20 (2003) 170-171] in the first population-based study based on the revised diagnostic criteria of ADA-1997 and WHO-1998. In comparison with our community-based survey done in 1990 in suburban and rural areas of Nepal, the current data show a surprisingly rapid increase in the prevalence of diabetes in the Nepalese population. In our 1990 study, diabetes and IFG, respectively, were present in 1.4 and 2.5% of people > or =20 years old in suburban village (Bhadrakali) compared with 0.3 and 0.7% in a rural village (Kotyang). In a short communication, Singh and Bhattarai found the rates to be 14.6 and 9.1% in urban areas, and 2.5 and 1.3% in rural areas. This phenomena appears to have been influenced more by rapid urbanization and changes in lifestyles after the ongoing democratic movements that have taken place since 1990 in Nepal. Moreover, our new analysis of the data provide baseline features for the planning of health care policy and establishment of medical priorities in modern day Nepal.

Tissue distribution of antihypertensive dipeptide, Val-Tyr, after its single oral administration to spontaneously hypertensive rats.

The distribution of an antihypertensive dipeptide, Val-Tyr (VY), in the tissues of spontaneously hypertensive rats (SHR) was investigated in this study. A single oral administration of VY (10 mg/kg) to 18-week-old SHR resulted in a prolonged reduction of systolic blood pressure (SBP) up to 9 h (SBP0h 198.0+/-3.6 mmHg; SBP9h 154.6+/-3.5 mmHg). As a result of VY determination, a roughly 10-fold higher increment of plasma VY level was observed at 1 h than that at 0 h, whereas thereafter the level declined rapidly. In tissues, VY was widely accumulated in the kidney, lung, heart, mesenteric artery and abdominal aorta with the area under the curve over 9 h of more than 40 pmol h/g tissue; of these a higher VY level was observed in the kidney and lung. In addition, a mean resident time (MRT) for each tissue (>5 h except for liver) revealed that VY preferably accumulated in the tissues rather than in the plasma (MRT 3.8 h). Significant reductions of tissue angiotensin I-converting enzyme activity and angiotensin II level were found in the abdominal aorta as well as in the kidney, suggesting that these organs could be a target site associated with the antihypertensive action of VY.

Bancroftian filariasis in Nepal: a survey for circulating antigenemia of Wuchereria bancrofti and urinary IgG4 antibody in two rural areas of Nepal.

Serum and urine samples were randomly collected from residents in two rural areas at different altitudes in Nepal, and were examined for Wuchereria bancrofti antigens and antibodies (IgG4) to filarial antigens, respectively. In Judigaun, located at 900 m in altitude, 25.2% of 238 serum samples were positive for antigen, and 50.8% of 244 urine samples were positive for antibody. The level of IgG4 antibodies was higher among antigen positive individuals than among the antigen negatives. In Kotyang, located at 1100-1300 m, the prevalence of antigenemia was 15.4% of 117 serum samples.

A 17-year follow-up study of hypertensive and normotensive male university students in Japan.

The aim of the present study was to determine the disease course of hypertensive male university students followed for 8 to 26 years (average, 17 years) after graduation. Subjects were classified into two groups. 1) A hypertensive group (H-group) consisting of 338 conclusively hypertensive male students followed from 1973 to 1990 at the Institute of Health Science, Kyushu University. Their ages ranged from 20 to 27 years, and all had high blood pressure (BP) of 140 mmHg or greater in systole (SBP) and/or 90 mmHg or greater in diastole (DBP) at a regular health check. This was confirmed by BP measurements for 3 days within 1 week. 2) A normotensive control group (N-group) consisting of 732 normotensive students (110-124 SBP/60-74mmHg DBP) for whom faculty, age, sex, height, weight, and examination period were matched to the H-group as closely as possible. In 1997, each subject was sent a questionnaire with items on height, weight, sitting BP, pulse rate, family history of hypertension, lifestyle habits (such as drinking and smoking), stress and personality type. Completing the questionnaire were 177 (52.4%) of the H-group and 206 (28.1%) of the N-group subjects. Hypertension continued in 44.6% of the H-group subjects, whereas 9.2% of the N-group subjects became hypertensive. The rate of hypertension at the end of the investigation was significantly higher in those subjects who had a family history of hypertension than in those who did not. Weight gain (+15.1%) was the highest in H-group subjects who were initially normotensive. These subjects showed a significantly higher incidence of smoking and drinking than the other subjects. These results confirmed lifestyle to be one of the most important factors in keeping BP normal throughout life and also suggested that fundamental health education should be introduced at an early age.

Estimated protein intake and blood pressure in a screened cohort in Okinawa, Japan.

We examined the relation between protein intake and blood pressure in a screened cohort in Okinawa, Japan. A total of 1,299 screened subjects, 885 men and 414 women, were examined at the Okinawa General Health Maintenance Association. Daily intake of sodium (Na) and potassium (K) was estimated from Na, K, and creatinine excretion by the method of Kawasaki et al., and daily protein intake was estimated by the method of Maroni et al. as the estimated daily urinary excretion of urea nitrogen. Mean (SD) daily protein intake was 71.8 (18.6) g in men and 54.0 (13.5) g in women, and the mean (SD) daily protein intake per unit kg body weight was 1.1 (0.2) g/kg in men and 1.0 (0.2) g/kg in women. In men, both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in those with lower protein intake (LP; < 1.0 g/kg/day) than in those with higher protein intake (HP; > or = 1.0 g/kg/day) (p < 0 .05 for DBP). In women, both SBP and DBP were higher in those with LP than in those with HP, but these differences were not statistically significant. However, urinary excretion of both Na and K was lower in those with LP than in those with HP, respectively, both in men and women (p < 0.0001). In summary, estimated daily protein intake was about 1.1 g/kg in men and 1.0 g/kg in women. Despite the higher urinary excretion of Na, both SBP and DBP tended to be lower in those with higher daily protein intake, particularly in men.

Depressor effect induced by dipeptide, Val-Tyr, in hypertensive transgenic mice is due, in part, to the suppression of human circulating renin-angiotensin system.

1. In the present study, the depressor action of the dipeptide Val-Tyr, with an in vivo antihypertensive effect, was investigated in transgenic mice carrying the human renin gene cross-mated with mice bearing the human angiotensinogen gene (Tsukuba Hypertensive Mouse; THM). 2. Single oral administration of Val-Tyr (0.1 mg/g) to 11-week-old THM resulted in a prolonged reduction of blood pressure for up to 9 h. The effect clearly demonstrated that the Val-Tyr absorbed acted on the enhanced human renin-angiotensin system (RAS). 3. After Val-Tyr administration, an approximate eightfold higher increment of plasma Val-Tyr was observed at 1 h (3406 +/- 211 fmol/mL plasma) compared with the level observed at 0 h; plasma concentrations of Val-Tyr returned to baseline levels at 6 h. 4. Transient changes in plasma concentrations of angiotensin (Ang) I and AngII only at 1 h were consistent with plasma Val-Tyr concentrations, suggesting that that the long-lasting reduction in blood pressure was achieved by the latent hypotensive mechanism of Val-Tyr and not by transient suppression of the circulatory RAS. 5. Ageing of the THM greatly affected the depressor action of Val-Tyr, with no significant reduction in blood pressure observed in 18- and 24-week-old THM.

[Antihypertensive effect and safety evaluation of vegetable drink with peptides derived from sardine protein hydrolysates on mild hypertensive, high-normal and normal blood pressure subjects].

A randomized double-blind placebo-controlled study was conducted on 63 subjects to determine the antihypertensive effect of a vegetable drink in which sardine protein hydrolysates containing a dipeptide, Valyl-Tyrosine (VY), were incorporated. The subjects, consisting of people with mild hypertension, high-normal blood pressure and normal blood pressure, were randomly divided into test (male/female = 25/6, average age 50.1 +/- 10.4 years old) and control groups (26/6, 49.0 +/- 5.0). Each subject in the test group was given 195 g of the vegetable drink containing 0.5 g of sardine peptides (sardine protein hydrolysates) with 0.4 mg of VY (test drink) once a day for 13 weeks in a row, and subjects in the control group were given the same amount of the vegetable drink without sardine peptides (control drink) in the same manner. In the test group, 40 subjects with mild hypertension or high-normal blood pressure (130 mmHg < or = systolic blood pressure (SBP) < 160 mmHg and/or 80 mmHg < or = diastolic blood pressure (DBP) < 100 mmHg) showed a significant decrease in SBP, from 142.0 +/- 10.3 mmHg at the start of the test to 134.4 +/- 11.1 mmHg during the first week of the test period, after which similar values were seen throughout the test period (13 weeks). Compared to the control group, the difference in SBP from baseline was statistically significant in the test group throughout the intake period. DBP also decreased significantly from 88.0 +/- 7.9 mmHg at baseline to 83.5 +/- 8.6 mmHg after 13 weeks. In the control group, SBP and DBP were 140.8 +/- 8.4 mmHg and 90.5 +/- 6.6 mmHg respectively at the start of the test, and neither decreased during the test period. In subjects with normal blood pressure, neither those in the test group nor those in the control group showed a significant change in SBP and DBP during the test period. An excessive ingestion test was performed on 25 subjects with hypertension, mild hypertension, high-normal blood pressure, and normal blood pressure by giving 585 g (3 times the recommended amount of intake) of the test drink for 14 days in a row. As a result, a significant decrease of blood pressure was observed in the hypertension, mild hypertension and high-normal blood pressure groups, but no excessive decline in blood pressure or any side-effects were associated with any subjects during the test period. In the groups with normal blood pressure, the excessive ingestion of the test drink did not affect blood pressure. In these two studies, physical check-ups and biochemical analyses of blood and urine were also conducted in all subjects, and no abnormalities were observed. These results suggest that the test drink containing sardine protein hydrolysates exhibited the antihypertensive effect in only the subjects with mild hypertension or high-normal blood pressure. No adverse effects were observed in either hypertensive or normotensive subjects.

Urinary excretion of sodium and potassium in a screened cohort in Okinawa, Japan.

Information regarding daily intake of sodium (Na) is useful for both normotensive and hypertensive subjects. We measured urinary excretion of sodium (U-Na) and urinary excretion of potassium (U-K) to estimate daily salt intake in a cohort of health screening subjects in Okinawa, Japan. Urine samples were obtained from 2,411 subjects (1,554 men and 857 women) who were examined on a half-day dry-doc at the Okinawa General Health Maintenance Association (OGHMA). Four hundred and one subjects were examined twice, once between September and November in 1997, and once between September and November in 1998. The mean U-Na was 182 mEq/day for men and 176 mEq/day for women. The mean U-K was 54 mEq/day for men and 50 mEq/day for women. U-Na was higher in young men, and U-K was lower in young women. In both men and women, smokers had a significantly lower Na excretion compared to nonsmokers. Subjects treated for hypertension had a significantly lower Na excretion (173 mEq/day) compared to subjects not treated for hypertension (192 mEq/day). Our findings suggest that Na excretion in screened subjects in Okinawa is lower than the national average. Sodium excretion, however, was higher in young men than in elderly subjects, and K excretion was lower in young women than in elderly subjects. Both trends are disadvantageous for controlling hypertension.

Absorption of Val-Tyr with in vitro angiotensin I-converting enzyme inhibitory activity into the circulating blood system of mild hypertensive subjects.

The change in plasma level of dipeptide, Val-Tyr (VY), with in vitro angiotensin I-converting enzyme inhibitory activity was investigated after a single oral administration of a VY-drink at doses of 0, 6 or 12 mg given to mild hypertensive subjects. During this protocol for up to 24 h after the intake, patient/subject blood pressure (BP) was measured for a 15 min period at designated times (0, 1, 2, 4, 8, 24 h) with the individual supine. Based on the VY determination, the maximal increment of plasma VY level was observed over the second hour postprandially (12 mg-dose; 2041+/-148 fmol/ml-plasma). In addition, the plasma VY level increased with the VY dosage. However, no marked BP change was observed with the increase of plasma VY level, suggesting that VY did not exert an acute hypotensive effect. The area under the curve at 12 mg-dose was estimated to be 8644+/-420 fmol x h/ml-plasma, comparable to that in normotensive subjects. This finding suggests that absorption of VY would not be influenced by a complaint of hypertension.

Latent production of angiotensin I-converting enzyme inhibitors from buckwheat protein.

The latent production of angiotensin I-converting enzyme (ACE) Inhibitors from tartary buckwheat (BW) was investigated, and the peptides responsible for ACE inhibition characterized. Intact buckwheat was found to exhibit ACE inhibitory activity having an IC50 value of 3.0 mg/ml. The activity of the protein fraction (IC50: 0.36 mg protein/ml) was not enhanced by pepsin treatment. Pepsin, followed by chymotrypsin and trypsin hydrolysis, resulted in a significant increase in the ACE inhibitory activity (IC50: 0.14 mg protein/ml). The rutin contained in the buckwheat did not exhibit any ACE inhibition. A single oral administration of BW digest lowered the systolic blood pressure of a spontaneously hypertensive rat. Thus, BW proteins offer a potential resource for producing ACE inhibitory peptides during the digestion process. From the di-/tri-peptide fraction (DTPF) of the BW digest, inhibitory peptides were identified. The magnitude (%) of the total ACE inhibitory contribution of each identified peptide, relative to the overall inhibition of the DTPF, was about 41%.

Effects of a 1 day fast on biohumoral variables associated with human circadian rhythmicity.

1. The aim of the present study was to investigate the effects of a short (1 day) fast by testing biohumoral variables associated with the human circadian rhythm. 2. Fifteen clinically healthy male volunteers (32 +/- 8 years old) participated in the study. Subjects were fed a control diet for 7 days. The last day was a control day and the following 8th day was the fasting day. Each subject was asked to collect urine seven times over a 24 h period. Chemical and hormonal variables were measured in each fractionated urine specimen. The time- qualified urinary excretion rates were biometrically analysed using conventional and chronobiological methods. 3. During fasting, significant incremental changes were detected in the urinary excretion rates of potassium, aldosterone, 17-hydroxycorticosteroids and adrenaline and significant decremental changes were detected in the excretion rates of sodium, chloride, creatinine, urea nitrogen, uric acid, 17-ketosteroids, noradrenaline and dopamine. The circadian rhythmicity of the variables was well preserved and remained almost stable throughout the fasting phase. 4. Fasting affected the mean oscillatory levels and oscillatory amplitudes of variables, suggesting that nutrients may have played roles as tonic and phasic modulators on the mechanisms that physiologically regulate ircadian rhythmicity.

Val-Tyr as a natural antihypertensive dipeptide can be absorbed into the human circulatory blood system.

1. Intact absorption of the bioactive dipeptide Val-Tyr (VY), with in vivo antihypertensive ability in normotensive human subjects, was investigated. 2. As a result of a single oral administration of VY, the VY absorption curve occurred maximally over the second hour postprandially; a greater than 10-fold higher increment of VY following a dose of 12 mg was observed in the plasma at 2 h compared with the baseline concentration of VY at 0 h (1934 +/- 145 vs 159 +/- 11 fmol/mL plasma, respectively). 3. Plasma VY levels increased with dose administered (3, 6 and 12 mg), suggesting that exogenous VY could be absorbed intact into the human blood depending on the dose. The elimination half time (t1/2) of VY was estimated to be 3.1 h. The area under the curve for the 12 mg VY dose was 9185 +/- 688 fmol small middle doth/mL plasma.