Eiji Miyajima

Effects of Insufficient Sleep on Blood Pressure Monitored by a New Multibiomedical Recorder

Blood pressure varies in relation to factors such as physical activity, body position, ambient temperature, and autonomic nervous system activity. Therefore, we have developed a portable multibiomedical (PMB) recorder that monitors five parameters: indirect blood pressure, physical activity, body position, ambient temperature, and RR interval of the electrocardiogram. In the present study, we applied the PMB recorder over a 24-hour period to study the effect of insufficient sleep on blood pressure in subjects doing extensive overtime work. The parameters listed above were measured by the PMB recorder throughout a normal workday (mean period of sleep, 8 hours) and throughout a day with insufficient sleep (mean period of sleep, 3.6 hours) in 18 male technical workers aged 23 to 48 years old. Blood pressure (mean systolic/diastolic pressure +/- SD) significantly increased the day after a sleep-insufficient night (129 +/- 8/79 +/- 6 mm Hg) compared with the day after a normal night (123 +/- 8/76 +/- 7 mm Hg, P<.05). However, ambient temperature, mean number of steps per minute, and percentage of time spent in a standing position showed no significant difference between these days. Spectral analysis of RR intervals showed that the ratio of the low-frequency component on the RR power spectrum (0.05 to 0.15 Hz) to the high-frequency component (0.15 to 0.40 Hz) was higher on the sleep-insufficient day (2.17 +/- 0.37 versus 1.81 +/- 0.37), as was the urinary excretion of norepinephrine (P<.05). Heart rate was significantly higher on the sleep-insufficient day (81 +/- ll versus 76 +/- 8 beats per minute), after the data of two subjects with abnormal levels of physical activity were excluded (P<.Ol). These data suggest that lack of sleep may increase sympathetic nervous system activity on the following day, leading to increased blood pressure. The PMB recorder was useful for precisely evaluating the relationship between blood pressure and environmental factors.

Age-related changes in muscle sympathetic nerve activity in essential hypertension.

To investigate the pathophysiological role of the sympathetic nervous system in essential hypertension, this study recorded the muscle sympathetic nerve activity (MSNA) of the tibial nerve and examined the age-related changes in patients with essential hypertension and in normotensive persons. There were 43 normotensive subjects (16–69 years old) and 63 patients with essential hypertension (18–67 years old) in the study. The MSNA at rest, recorded by microneurography, was evaluated by burst rate (bursts/min), burst incidence (bursts/100 heart beats), and spike frequency (spikes/min). The MSNA recording showed a high reproducibility with a correlation coefficient of 0.86 (p < 0.0l) in repeated studies. The MSNA was significantly greater in the hypertensive patients than in the normotensive subjects, irrespective of activity units (p < 0.0l), and this finding was consistent in the young (30 years old or less), middle-aged (31–50 years old), and old groups (51 years old or more). Furthermore, MSNA showed a significant positive correlation with age both in the normotensive subjects (r = 0.43, p < 0.01 for burst rate; r = 0.49, p < 0.01 for burst incidence; and r = 0.50, p < 0.01 for spike frequency) and in the hypertensive patients (r = 0.40, p < 0.01 for burst rate; r = 0.44, p < 0.01 for burst incidence; and r = 0.40, p < 0.01 for spike frequency). Although there was a significant positive correlation between plasma norepinephrine concentration and MSNA in the hypertensive patients and the normotensive subjects, the difference in plasma norepinephrine concentration between the two groups was not significant at any age level. These results indicate that sympathetic nerve activity is increased in patients with essential hypertension at any age level and plays a long-term role in the development and maintenance of blood pressure elevation.

Muscle sympathetic nerve activity in renovascular hypertension and primary aldosteronism.

Previous studies, including our own, have demonstrated that muscle sympathetic nerve activity (MSNA) is increased in patients with essential hypertension compared with normotensive subjects. However, the features of sympathetic nerve activity are still unknown in secondary hypertension. We examined MSNA in eight patients with renovascular hypertension and in 11 patients with primary aldosteronism. Twenty patients with essential hypertension and 20 normotensive subjects who were age-matched to the patients with renovascular hypertension and those with primary aldosteronism were also studied. The MSNA of a bundle of the tibial nerve was recorded by microneurography in supine subjects and expressed as both burst rate (bursts/min) and burst incidence (bursts/100 heart beats). Plasma renin activity and the plasma concentration of angiotensin II and aldosterone were also measured. MSNA was increased in the patients with renovascular hypertension compared with the patients with primary aldosteronism and those with essential hypertension and the normotensive subjects (p<0.01 for each). MSNA was decreased in the patients with primary aldosteronism compared with those with essential hypertension (p<0.01), and it was smaller than in the normotensive subjects (p<0.l). Furthermore, MSNA, plasma renin activity, and the plasma concentration of angiotensin II decreased significantly in five patients with renovascular hypertension 4–10 days after successful percutaneous renal angioplasty. Thus, the changes in MSNA seem to characterize the patbophysiology of renovascular hypertension and primary aldosteronism. Activation of the renin-angiotensin system may be involved in the increase in the central outflow of sympathetic nerve activity, thus exacerbating hypertension in patients with renovascular hypertension.

Circadian variation of haemodynamics in patients with essential hypertension: comparison between early morning and evening

Objective An increased incidence of cardiovascular accidents in the morning has been reported, but the reason why is not clear. We measured 24-h haemodynamics and focused on its change in the morning. Design To study the circadian variation of haemodynamics, we recorded 24-h direct blood pressure and electrocardiogram using a telemetry method, in 21 untreated inpatients with essential hypertension, and measured cardiac output using the dye-dilution method in the morning, in the evening and during sleep. We also determined the beat-to-beat cardiac output (using the pulse-contour method), the total peripheral resistance and the ratio of low- to high-frequency components (using power spectral analysis of the R-R interval during 24 h), and made comparisons between morning and evening values. Results Both systolic and diastolic blood pressure increased rapidly in the early morning. Although the comparison of blood pressure between morning and evening showed no difference, total peripheral resistance and low- to high-frequency ratio were significantly higher in the morning than in the evening, but cardiac output was lower in the morning. Conclusions Sympathetic nervous activity and vascular resistance seem to be higher in the morning than in the evening, and these haemodynamic changes may stress the cardiovascular system.

Impaired baroreflex changes in muscle sympathetic nerve activity in adolescents who have a family history of essential hypertension

To evaluate the baroreflex changes and basal sympathetic vasomotor tone among three groups of adolescent normotensives or borderline hypertensives with and normotensives without a family history of hypertension, we continuously recorded muscle sympathetic nerve activity, arterial pressure and heart interval. Baroreflex slopes were calculated either by plotting the heart interval against the preceding peak systolic arterial pressure, or by relating the percentage changes in muscle sympathetic nerve activity to the mean changes in systolic arterial pressure produced by intravenous phenylephrine. The baroreflex slopes for the heart interval were significantly smaller in borderline hypertensive offspring (14 ± 2 ms/mmHg) than in control normotensives (23 ± 2 ms/mmHg) or normotensive offspring (19 ± 3 ms/mmHg), whereas those for muscle sympathetic nerve activity were significantly smaller both in normotensive offspring (-8.3 ± 1.0%/mmHg) and borderline hypertensive offspring (-7.9 ± 0.5%/mmHg) than in control normotensives (-16.3 ± 1.4%/mmHg). Baseline muscle sympathetic nerve activity was higher in borderline hypertensive offspring (20.1 ± 3.0 bursts/min) than in control normotensives (10.1 ± 1.2 bursts/min) or normotensive offspring (12.8 ± 1.4 bursts/min), and also the depressor responses to trimethaphan were significantly enhanced in borderline hypertensive offspring [-19.2 ± 2 versus 14 ± 1 (normotensive offspring) or 12 ± 2 (control normotensives)]. These results indicate that baroreflex inhibition of muscle sympathetic nerve activity was reduced in adolescents with a family history of hypertension even when they were normotensive. This reduced reflex sympatho-inhibition could lead to the development of hypertension by increasing sympathetic vasomotor tone.

Statistical base value of 24-hour blood pressure distribution in patients with essential hypertension.

The purpose of this study was to calculate statistically the minimum (base) blood pressure (BP) of nighttime (sleep-time) BP values obtained by ambulatory BP monitoring (ABPM) and to investigate its clinical significance. Twenty-four-hour recording of ECG with ABPM was performed directly (n=89) or indirectly (n=117) in 206 patients with essential hypertension. A telemeter was used for the direct method and a multi-biomedical recorder (TM2425) was used for indirect measurement. First, minimum heart rate (HR0=60/RR0) was determined from sleep-time ECG. The mean product of sleep-time diastolic BP (DBP) and pulse interval (RR) was divided by RR0 to obtain DBP0 [DBP0=(DBPxRR)s/RR0]. The correlation between systolic BP (SBP) and DBP was used to determine SBP0 corresponding to DBP0. Statistical base mean BP (MBP0) was calculated from these values, and its reproducibility and relation to hypertension severity were investigated. MBP0 values were similar to true base values of sleep-time MBP obtained by the direct method (mean+/-SD difference, 2.0+/-4.2 mm Hg). Direct MBP0 criteria predicted hypertension severity (mild, moderate, or severe target organ damage) more accurately (predictive accuracy, 89%) than daytime MBP criteria (53%, P<0.01). Almost the same results were obtained using indirect MBP0 criteria. Day-to-day indirect MBP0 variation (mean absolute difference) was smaller (2.4+/-1.8 mm Hg) than day-to-day daytime and nighttime MBP variation (6.3+/-5.3 and 5.4+/-3.4 mm Hg, respectively; n=61, P<0.01), and the correlation coefficient between day-to-day variations of daytime MBP and physical activity (measured by an acceleration sensor) was 0.38 (P<0.05). In conclusion, statistical base BP was almost equal to true base (minimum) BP of sleep-time BP distribution. It was closely related to the severity of hypertensive organ damage, was highly reproducible, and is considered likely to serve stochastically and physiologically as a representative BP value in an individual subject.

ANGIOTENSIN II BLUNTS, WHILE AN ANGIOTENSIN-CONVERTING ENZYME INHIBITOR AUGMENTS, REFLEX SYMPATHETIC INHIBITION IN HUMANS*

1. The role of angiotensin (Ang)II in and the effects of angiotensin‐converting enzyme (ACE) inhibitors on the regulation of sympathetic neural activity were examined in humans.

Blood pressure during sleep: Antihypertensive medication

To investigate whether excessive reduction of blood pressure (BP) by antihypertensive medications correlates with myocardial infarction, especially during sleep in elderly patients, we used telemetry and cuvette dye-dilution methods to assess the direct BP and the hemodynamics of 68 inpatients with essential hypertension during wakefulness and sleep. There were 25 patients greater than or equal to 60 years old (OH-group) and 43 were less than or equal to 59 years old (YH-group). Of the OH-group, 36% showed high BP during the day, with marked decreases (minimum BP less than 110/70 mm Hg) during sleep. Average cardiac index (CI) of the OH-group was low during wakefulness and extremely low during slow-wave sleep. Changes of mean BP in the OH-group correlated with changes in total peripheral vascular resistance index (TPRI) during sleep, but this correlation was not observed in the YH-group. The antihypertensive effects on nocturnal BP of the various medications was: central adrenergic inhibitors less than or equal to beta blockers with intrinsic sympathomimetic activity less than or equal to alpha (alpha beta) blockers less than or equal to angiotensin-converting enzyme inhibitors less than or equal to calcium antagonists. Because BP and CI were found to be very low and TPRI seems to play an important role in BP regulation in sleeping elderly patients, excessive antihypertensive medication may be harmful to this subgroup. However, because the effects on nocturnal BP differ among various antihypertensive treatments, further research is required on the relation between antihypertensive medication and the hemodynamics of sleeping elderly hypertensive patients.

Antihypertensive effects and pharmacokinetics of single and consecutive administration of doxazosin in patients with mild to moderate essential hypertension.

A single dose of doxazosin, a long-acting postsynaptic α1-adrenoceptor antagonist, was administered to seven patients with essential hypertension. Following administration of a single dose, all the patients except one who was forced to be discharged from the hospital for work, continuously received doxazosin once daily (o.d.) for evaluation of its consecutive dosing effect. The antihypertensive effect, pharmacokinetics, and effects on the plasma renin activity (PRA) of doxazosin were investigated. Following a 2-mg single dose of doxazosin, the systolic blood pressure (SBP) decreased significantly up to 12 h. whereas consecutive dosing produced a significant decrease in the SBP up to 24 h and a significant decrease in the mean blood pressure up to 24 h as compared with placebo. The pharmacokinetic parameters of doxazosin in both single- and consecutive-dose study were 18.9 and 25.8 ng/ml in Cmax, 11.1 and 12.9 h in half life (t1/2), and 182.0 and 273.0 ng h/ml in area under the curve (AUC)240, respectively. No significant changes were observed in PRA and plasma concentration of catecholamines. Neither were there any observable changes in endogenous creatinine clearance and in the urinary excretion rates of Na, K. and Cl. Doxazosin was well tolerated by all patients, and no untoward effects were observed. Doxazosin effectively reduces blood pressure and, because of its long t1/2 and minimal effects on PRA catecholamines. and electrolytes, seems to be a useful antihypertensive agent in patients with essential hypertension.

Reduced sympathetic inhibition in salt-sensitive Japanese young adults

The purpose of our study was to investigate the sympathetic response to excess salt loading of 54 normotensive young adults with and without a family history of hypertension. We examined muscle sympathetic nerve activity, plasma concentration and urinary excretion of catecholamines, and ambulatory blood pressures during low (4 g NaCl) and high (16 g NaCl) salt diet intake. Ambulatory blood pressure and urinary excretion of catecholamines are known to be reduced during sleep. These parameters were therefore calculated during waking and sleeping periods. The subject was defined as salt-sensitive when mean ambulatory systolic pressure during the waking period was > or =3 mm Hg higher during high salt intake than during low salt intake (n = 26: 21.4+/-0.3 years old). When mean systolic pressure was either lower or equal during high salt intake than during low salt intake, the subject was defined as salt-resistant (n = 24: 21.3+/-0.3 years old). Muscle sympathetic nerve activity, plasma concentration and urinary excretion of norepinephrine in salt-resistant subjects were significantly reduced (P<.05) by salt intake, whereas plasma concentration of epinephrine was unchanged and urinary excretion of epinephrine was reduced. In contrast, urinary excretion of epinephrine in salt-sensitive subjects was significantly elevated (P<.05) during high salt intake, whereas muscle sympathetic nerve activity and urinary excretion of norepinephrine remained unchanged despite a significant increase (P<.01) of ambulatory blood pressure. Of the salt-sensitive subjects, 73% (19 of 26) had a positive family history of hypertension, whereas only 5 of 24 salt-resistant subjects had a positive family history. These data indicate that the inhibition of sympathetic activity during a high salt intake did not occur in salt-sensitive young adults, and this may be linked with a hereditary predisposition to hypertension.