Terukazu Kawasaki

Nocturnal Blood Pressure Fall on Ambulatory Monitoring in a Large International Database

A wide range of definitions is used to distinguish subjects in whom blood pressure (BP) falls at night (dippers) from their counterparts (nondippers). In an attempt to standardize the definition of nondipping, we determined the nocturnal BP fall and night-day BP ratio by 24-hour ambulatory monitoring in 4765 normotensive and 2555 hypertensive subjects from 10 to 99 years old. In all subjects combined, the systolic/diastolic nocturnal fall and corresponding ratio averaged (+/- SD) -16.7 +/- 11.0/ -13.6 +/- 8.1 mm Hg and 87.2 +/- 8.0%/83.1 +/- 9.6%, respectively. In normotensive subjects, the 95th percentiles were -0.3/-1.1 mm Hg for the nocturnal fall and 99.7%/98.3% for the night-day ratio. Both the fall and ratio showed a curvilinear correlation with age. The smallest fall and largest ratio were observed in older (> or = 70 years) subjects. A higher BP on conventional sphygmomanometry was associated with a larger systolic (partial r = .11) and diastolic (r = .12) nocturnal BP fall. The diastolic (r = .08) but not the systolic night-day ratio increased with higher conventional BP. The nocturnal BP fall was larger and the corresponding night-day ratio smaller in oscillometric (n = 5884) than in auscultatory (n = 1436) recordings, in males (n = 3730) than in females (n = 3590), and in Europe (n = 4556) than in the other continents (n = 2764). The distributions of the nocturnal BP fall and night-day ratio showed considerable overlap among normotensive and hypertensive subjects, but the overlap tended to be larger for the ratio than for the fall. Of all subjects, 3.2% had systolic and diastolic ratios of 100% or more. With adjustments applied for confounders, the probability of being a nondipper increased 2.8 times (95% confidence interval, 2.0-4.0) from 30 to 60 years and 5.7 times (4.4-7.4) from 60 to 80 years. The odds ratios were 1.0 (0.8-1.4) for males versus females. 1.6 (1.2-2.1) for subjects with definite hypertension versus normotensive subjects, 2.4 (1.2-4.7) for Asians (n = 2213, 96% Japanese) versus inhabitants of the other continents, and 2.4 (1.5-3.8) for subjects examined with auscultatory versus oscillometric devices. In conclusion, the mathematical definition of nondipping, ie, having a night-day ratio of 100% or more for systolic and diastolic BPs, closely approximated the 95th percentiles of the night-day ratio in normotensive subjects. The ratio depends less on BP level than the nocturnal BP fall and is therefore to be preferred in the definition of dipping status. Notwithstanding the present findings, the reproducibility of nondipping and its prognostic significance need further clarification.

A simple method for estimating 24 h urinary sodium and potassium excretion from second morning voiding urine specimen in adults.

1. An assessment was made of the extent sodium (Na) and potassium (K) intake can be estimated from Na, K and creatinine (Cr) content of a second morning voiding urine (SMU) specimen collected within 4 h after the first voiding upon awakening but before breakfast in 159 clinically healthy, free‐living individuals (20–79 years). The SMU and the rest of 24 h urine specimens for a 3–5 day period were collected.

Antihypertensive effect of valyl-tyrosine, a short chain peptide derived from sardine muscle hydrolyzate, on mild hypertensive subjects.

The present study was conducted to determine whether Valyl-Tyrosine (VY) has an antihypertensive effect on high-normal blood pressure and mild essential hypertension, as well as spontaneous hypertensive rats (SHR). A randomised double-blind placebo-controlled study was carried out on 29 volunteers. A 100-ml drink containing 3 mg of VY and a 100-ml placebo drink were prepared. The subjects were grouped as VY(16M/1F, 45.5 ± 3.2 years, 146.4 ± 2.3/90.5 ± 1.8 mm Hg) and the placebo (P) (11 M/1F, 48.8 ± 3.0 years, 145.5 ± 2.4/92.3 ± 1.8 mm Hg). At 3 weeks of the control (C) period, a VY- or P-drink was administered twice a day for 4 weeks in the experimental (E) period and during the 4-week recovery period, neither drink was given to either group. Blood pressure (BP) was measured every week in the morning in the sitting position. Blood specimens were taken on the last day of the C and E periods. In the VY-group, reduction in systolic (S) and diastolic (D) BP was 9.7 and 5.3 mm Hg (P < 0.001) at 1 week, and 9.3 and 5.2 mm hg (P < 0.001) at 4 weeks, following the start of the e period, respectively. neither sbp nor dbp changed in the p-group. bp in the vy-group increased gradually by the end of the recovery period. plasma angiotensin (ang) i and vy concentrations significantly increased while ang ii and aldosterone significantly decreased after vy administration in the vy-group. vy appeared to have a significant antihypertensive effect on mild hypertensive subjects via ang i-converting enzyme inhibition, as well as shr, but no adverse effects could be detected at all.

Ambulatory blood pressure in normotensive and hypertensive subjects: Results from an international database

Objective To delineate more precisely an operational threshold for making clinical decisions based on ambulatory blood pressure (ABP) measurement by studying the ABP in subjects who were diagnosed as either normotensive or hypertensive by conventional blood pressure (CBP) measurement. Subjects: Twenty-four research groups recruited 7069 subjects. Of these, 4577 were normotensive (CBP 140/90 mmHg), 719 were borderline hypertensive (systolic CBP 141–159 mmHg or diastolic CBP 91–94 mmHg) and 1773 were definitely hypertensive. Of the subjects in the last of these categories, 1324 had systolic hypertension (systolic CBP 21 60 mmHg) and 131 0 had diastolic hypertension (diastolic CBP 295 mmHg). Combined systolic and diastolic hypertension was present in 861 subjects. Hypertension had been diagnosed from the mean of two to nine (median two) CBP measurements obtained at one to three (median two) visits. Results The 95th centiles of the ABP distributions in the normotensive subjects were (systolic and diastolic, respectively) 133 and 82 mmHg for 24-h ABP, 140 and 88mmHg for daytime ABP and 125 and 76mmHg for night-time ABP, respectively. Of the subjects with systolic hypertension, 24% had 24-h systolic ABP 4 33 mmHg. Similarly, 30% of those with diastolic hypertension had 24-h diastolic ABP 432 mmHg. The probability that hypertensive subjects had 24-h ABP below these thresholds tended to increase with age and was two- to fourfold greater if the CBP of the subject had been measured at only one visit and if fewer than three CBP measurements had been averaged for establishing the diagnosis of hypertension. By contrast, for each 1 O-mmHg increment in systolic CBP, this probability decreased by 54% for 24-h systolic ABP and by 26% for 24-h diastolic ABP, and for each 5-mmHg increment in diastolic CBP it decreased by 6 and 9%, respectively. In comparison with 24-h ABP, the overlap in the daytime and night-time ABP between normotensive and hypertensive subjects was of similar magnitude and was influenced by the same factors. Conclusions The ABP distributions of the normotensive subjects included in the present international database were not materially different from those in previous reports in the literature. One-fifth to more than one-third of hypertensive subjects had an ABP which was below the 95th centile of the ABP of normotensive subjects, but this proportion decreased if the hypertensive subjects had shown a higher CBP upon repeated measurement. The prognostic implications of elevated CBP in the presence of normal ABP remain to be determined.

Short report: Ambulatory blood pressure in normotensive compared with hypertensive subjects

Objective: To delineate more precisely an operational threshold for making clinical decisions based on ambulatory blood pressure (ABP) measurement by studying the ABP in subjects who were diagnosed as either normotensive or hypertensive by conventional blood pressure (CBP) measurement. Subjects: Twenty-four research groups recruited 7069 subjects. Of these, 4577 were normotensive (CBP ≥140/90mmHg), 719 were borderline hypertensive (systolic CBP 141–159mmHg or diastolic CBP 91–94mmHg) and 1773 were definitely hypertensive. Of the subjects in the last of these categories, 1324 had systolic hypertension (systolic CBP ≤160 mmHg) and 1310 had diastolic hypertension (diastolic CBP ≤95 mmHg). Hypertension had been diagnosed from the mean of two to nine (median two) CBP measurements obtained at one to three (median two) visits. Results: The 95th centiles of the 24-h ABP distributions in the normotensive subjects were (systolic and diastolic, respectively) 133 and 82 mmHg. Of the subjects with systolic hypertension, 24% had 24-h systolic ABP <133 mmHg. Similarly, 30% of those with diastolic hypertension had 24-h diastolic ABP <82 mmHg. The probability that hypertensive subjects had 24-h ABP below these thresholds tended to increase with age and was two- to fourfold greater if the CBP of the subject had been measured at only one visit and if fewer than three CBP measurements had been averaged for establishing the diagnosis of hypertension. By contrast, for each 10-mmHg increment in systolic CBP, this probability decreased by 54% for 24-h systolic ABP and by 26% for 24-h diastolic ABP, and for each 5-mmHg increment in diastolic CBP it decreased by 6 and 9%, respectively. Conclusions: The ABP distributions of the normotensive subjects included in the present international database were not materially different from those in previous reports in the literature. One-fifth to more than one-third of hypertensive subjects had an ABP which was below the 95th centile of the ABP of normotensive subjects, but this proportion decreased if the hypertensive subjects had shown a higher CBP upon repeated measurement. The prognostic implications of elevated CBP in the presence of normal ABP remain to be determined.

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.

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.

Antihypertensive and Natriuretic Effects of Less-Sodium Soy Sauce Containing γ-Aminobutyric Acid in Spontaneously Hypertensive Rats

We investigated the mechanism of the antihypertensive effect of less-sodium soy sauce containing γ-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.

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).

Determination of angiotensin metabolites in human plasma by fluorimetric high-performance liquid chromatography using a heart-cut column-switching technique

Fluorimetric column-switching HPLC method with naphthalene-2,3-dialdehyde (NDA) was developed for the determination of endogenous angiotensin (ANG) metabolites in human plasma. After one-step extraction to clean up the ultrafiltered plasma sample on the reversed HPLC system, the zone of the retention time of each ANG analyte was subjected to the NDA-derivatization. After putting into a first Phe-ODS (for ANG (3-4) and (5-8) determinations) or ODS column (for ANG I and II determinations), the heart-cut of the retention time of the NDA-ANG was separated on a second ODS column with a mobile phase containing 5 mM ion-pair reagent. Complete separation and good detection were accomplished within 2 h. Good linearity of the regression equation for all ANG analytes with the correlation coefficient of >0.993 as well as good reproducibility (C.V.<4.0%). Good agreement of the range of ANG II plasma level between the present (25-47 fmol/ml in plasma) and the radioimmunoassay methods (28-52 fmol/ml in plasma) indicated that the column-switching method could be applicable for the determination of endogenous smaller ANGs as well as for ANG I or II in plasma.