Circadian Rhythm of Blood Pressure: Internal and External Time Triggers

Diurnal blood pressure (BP) fluctuations are superimposed by a 24-h rhythm with usually lower levels during the night and higher levels during the day. In contrast to other rhythmic bioparameters, the diurnal BP rhythm is largely dependent on activity and sleep rather than on clock time. This has been demonstrated by the BP characteristics after shifted sleeping and working phases, during transition from sleep to wakefulness, and by the influence of sleep and activities on the 24-h BP curve during normal daily routines. Whereas the circadian rhythm of BP is predominantly governed by external time triggers, endogenous rhythmicity can only be detected by time microscopic analysis or in conditions where effects of external time triggers are almost excluded.     

Circadian Rhythm of Blood Pressure: Internal and External Time Triggers

Diurnal blood pressure (BP) fluctuations are superimposed by a 24-h rhythm with usually lower levels during the night and higher levels during the day. In contrast to other rhythmic bioparameters, the diurnal BP rhythm is largely dependent on activity and sleep rather than on clock time. This has been demonstrated by the BP characteristics after shifted sleeping and working phases, during transition from sleep to wakefulness, and by the influence of sleep and activities on the 24-h BP curve during normal daily routines. Whereas the circadian rhythm of BP is predominantly governed by external time triggers, endogenous rhythmic-ity can only be detected by time microscopic analysis or in conditions where effects of external time triggers are almost excluded.     

Consistent Changes in the Circadian Rhythms of Blood Pressure and Atrial Natriuretic Peptide in Congestive Heart Failure

We demonstrated in previous works that the circadian rhythms of blood pressure (BP) and atrial natriuretic peptide (ANP) are antiphasic in normal subjects and in essential hypertension. The aim of the present study was to assess the circadian rhythms of BP and ANP in 20 patients with stable congestive heart failure (CHF), divided into two groups of 10 according to their New York Heart Association functional class. A matched control group of 10 normal volunteers was also studied. Noninvasive BP monitoring at 15-min intervals was performed for 24 h. Peripheral blood samples were also obtained at 4-h intervals starting from 08:OO h. The mean (±SEM) circadian mesors of ANP plasma levels were 13.4 ± 1.7 pmol/L in the control group, 28.6 ± 2.4 pmol/L in the group of 10 patients in class 11, and 81.5 ± 12 pmol/L in the group of 10 patients in class 111-IV. In normal subjects, plasma ANP concentration was highest at 04:OO h (21.5 ± 2.7 pmol/L) and lowest at 16:OO h (8.8 ± 2.4 pmol/L; p < 0.01). Both groups of patients with CHF showed no significant circadian change in the plasma levels of ANP and also a significantly blunted circadian rhythm of BP. Cosinor analysis confirmed the loss of the circadian rhythms of ANP and BP in CHF patients. Our findings support the existence of a causal relationship between the circadian rhythms of ANP and BP.     

Circadian Rhythm of Blood Pressure and Heart Rate in Cardiopathic Patients Before and After Heart Transplantation

The aim of this study was to investigate the natural history of the circadian rhythm of blood pressure (BP) and heart rate (HR) in 10 patients with heart failure (class IV of the New York Heart Association), who underwent heart transplantation because of primary congestive cardiomyopathy. The control group was 10 age-matched clinically healthy subjects. The BP and HR monitor-ings were performed before and after transplantation. Preoperatively, analysis of variance and cosinor methods validated the occurrence of a statistically significant BP and HR circadian rhythm in cardiopathic patients. Over the 4 days after surgery, both the cosinor method and serial section analysis were unable to validate a 24-h periodicity for BP and HR in patients with heart transplants. Six months after surgery, the BP and HR circadian rhythm was not detected as well. One year after transplantation. the BP and HR circadian rhythm was statistically validated. The recovery of the BP and HR circadian rhythm 1 year after heart transplantation can be regarded as a clinical sign of a reacquired susceptibility to neurovegetative chronoregulation.     

Circadian Blood Pressure Rhythm in Primary and Secondary Hypertension

Circadian blood pressure variability was recorded in patients with primary hypertension and with different forms of secondary hypertension using ambulatory 24-h blood pressure measurement. A group of 20 patients with different forms of secondary hypertension was compared with a matched group of patients with primary hypertension. Although the mean 24-h blood pressure was not different between the two groups, the patients with secondary hypertension had significantly higher systolic blood pressure during sleep and higher systolic and diastolic blood pressure in the early morning, compared with the primary hypertension group. This nocturnal blood pressure fall was then investigated in various groups of patients with different forms of secondary hypertension and compared with normotensives and patients with primary hypertension. Patients with mild primary hypertension (n = 152) and with severe primary hypertension (n = 30) had the same blood pressure fall (14–16 mm Hg systolic and diastolic) during the night (23:OO–05:OO h) as normotensives (n = 20). However, in patients with renoparenchymal hypertension (n = 29), renovascular hypertension (n = 20), hyperaldosteronism (n = 6), and hyperthyroidism (n = 14), the nocturnal blood pressure fall was significantly (p < 0.01) reduced. One patient with coarctation ofthe aorta and nine patients with primary hyperparathyroidism and elevated blood pressure had a normal circadian blood pressure profile with a normal nocturnal blood pressure fall. The heart rate decrease during the night was equal in all patient groups. Ambulatory blood pressure measurement allows blood pressure recording under everyday conditions, including nighttime. In primary hypertension the blood pressure variability exhibits the same circadian variation as in normotension, showing a marked nocturnal fall. However, in different forms of secondary hypertension, blood pressure shows a blunted circadian curve. This could have important diagnostic and therapeutic implications.     

Circadian Rhythm of Blood Pressure and Heart Rate in Healthy Persons and Kidney Transplant Patients: Correlations with Activity

Fourteen diurnally active (07: 00–22: 39 h) normotensive healthy control subjects and 14 kidney transplant patients were studied by ambulatory blood pressure monitoring and wrist actigraphy simultaneously during one 24-h period. In the control group, circadian rhythms in systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressure, heart rate (HR), and wrist activity were documented by cosinor analysis with comparable afternoon peak times. In contrast, circadian rhythms with afternoon acrophases were detected only in HR and wrist activity in the patient group. The correlation of wrist activity with HR in controls and patients was comparable. Wrist activity and blood pressure were associated (r = 0.65 DBP and 0.54 SBP; p < 0.05) in controls, while in patients the relationship was weak or absent (r ranging from 0.02 SBP to 0.22 DBP). In 6 of 14 patients, BP and wrist activity were negatively correlated, reflecting the existence of nocturnal hypertension. In eight others, the correlation was small but positive. The 24-h pattern in BP and wrist activity in controls was comparably phased; however, this was not the case for the transplant patients, indicating the day-night pattern in blood pressure in this group is strongly dependent on pathologic phenomena rather than activity level and pattern.     

急性心力衰竭患者就诊时血压心率及血浆BNP水平与心功能的关系分析

目的:探讨急性心力衰竭(AHF)患者就诊时血压心率及血浆脑钠肽(BNP)水平与心功能的关系。方法:选取2013年4月-2014年12月于本院治疗的AHF患者134例,于就诊时测量患者血压、心率、BNP及心脏超声相关指标,分析血压心率及血浆BNP水平与心功能的关系。结果:就诊时SBP水平与左心室舒张末期直径及每搏输出量呈现正相关性(r=0.134、0.238,均P0.05);心率与每搏输出量、左室缩短率以及射血分数呈现负相关性(r=-0.177,-0.231,-0.197,均P0.05);BNP水平与左心室舒张末直径成正相关性,与左室缩短率以及射血分数呈负相关性(r=0.150、-0.247、-0.271,均P0.05)。结论:血压、心率以及BNP是临床诊断、评估AHF的重要指标。     

瑞舒伐他汀治疗慢性心力衰竭80例疗效观察

目的：评价瑞舒伐他汀治疗慢性心力衰竭的疗效。方法：选取2009年6月-2010年9月住院的心力衰竭患者80例,随机分为瑞舒伐他汀治疗组和对照组,对照组采用常规内科治疗。瑞舒伐他汀治疗组在常规内科治疗的基础上加用瑞舒伐他汀治疗。观察两组患者左心室舒张末期内径（LVEDD）,左心室射血分数（LVEF及临床疗效。结果：两组治疗前LVEDD及LVEF水平比较无差异（P〉0.05）,治疗后两组LVEDD水平明显下降,LVEF水平明显升高（P〈0.05）,瑞舒伐他汀治疗后LVEDD及LVEF水平改善均明显优于对照组（P〈0.05）。瑞舒伐他汀组临床疗效高于对照组（P〈0.05）。结论：瑞舒伐他汀可以改善慢性心力衰竭患者的心脏功能。     

ANP在大鼠高血压进展为心力衰竭中的作用

目的：探讨心房钠尿钛ANP 在高血压心力衰竭发展过程中的变化和氨氯地平保护心肌细胞的作用。方法：对大鼠行腹主动脉结扎术,术后随机选择40 只大鼠分为氨氯地平（中、高、低剂量）组以及模型组,另外选取10 只健康雄性SD 大鼠作为假手术组。采用ELISA 方法检测各组血清ANP 浓度变化。结果：随着心功能不全加重,ANP 水平逐渐上升。氨氯地平用药组大鼠的心功能改善明显优于模型组,ANP 明显降低,且随着氨氯地平用药量上升,心功能不断改善,ANP显著下降,P<0.05。结论：对血清ANP浓度进行测定能够反映出高血压大鼠模型心室功能不全及充血性心力衰竭严重程度。而氨氯地平能够影响机体的ANP 分泌对心肌细胞起到保护作用,从而有效抑制心室重构,延缓高血压心力衰竭疾病进展。     

快速心室起搏制备扩张型心肌病心力衰竭犬模型的方法学探讨

目的　应用快速心室起搏的方法制备扩张型心肌病心力衰竭犬模型 ,并对其方法学进行改进。方法　 6只成年健康杂种犬麻醉后先通过射频消融希氏束致Ⅲ度房室传导阻滞 ,再经静脉植入心内膜起搏电极 ,脉冲发射器为技术处理后的人用永久起搏器。起搏频率为 2 5 0次 min ,起搏时间持续 (2 3 6± 2 5 7)d。结果　除有相应症状、体征外 ,所有动物均成功制备为扩张型心肌病心力衰竭模型 ;B超和病理解剖检查证实有心脏扩大、心室壁变薄以及肝瘀血、肺瘀血 ;病理切片显示心肌细胞空泡变性、肝窦扩张充血、肺泡内含铁血黄素沉积。结论　改进后的快速心室起搏制备充血性心力衰竭动物模型的方法更为安全、可靠、实用。     

侧脑室注射硫化氢对大鼠血压和呼吸的调节作用

目的 探讨中枢硫化氢（H2S）对正常大鼠平均动脉血压的调节及其机制.方法 将微量H2S饱和盐溶液一次性和连续注射入麻醉大鼠侧脑室（ICV）,观察注药后血压、心率和呼吸的变化.结果 ICV一次性注射不同剂量的H2S饱和盐溶液后可引起血压先急剧降低而后迅速升高,心率减慢,呼吸幅度增加和呼吸频率减慢,并存在显著的剂量和时间依赖关系.ICV连续注射H2S可显著升高血压,但对心率和呼吸没有影响.ICV注射一次性注射K＋-ATP通道开放剂Pinacidil可显著的降低血压,但心率和呼吸没有显著变化;ICV一次性注射K＋-ATP通道阻断剂glibenclamide对血压、心率和呼吸没有显著的影响;但预先ICV注射glibenclamide可阻断H2S的降低血压和减慢心率的作用,对呼吸没有影响.预先静脉注射酚妥拉明对血压没有明显的影响,却显著抑制ICV给予H2S产生的升高血压减慢心率效应.结论 本工作提示H2S是调节心血管活动的一个重要的中枢活性因子,其降低血压的效应是通过K＋-ATP通道和影响呼吸有关系,而升压效应是通过激活交感神经的活性.     

Twenty-Four-Hour Blood Pressure Control: An Intraarterial Review

Intraarterial blood pressure monitoring has shown the circadian rhythm of blood pressure control. Blood pressures tend to be highest in the morning before falling gradually during the day to a nadir at 3:00 a.m. There is a slight rise in the late afternoon that may correspond to patients' attendance at hospital for calibration of the equipment. There is a small rise in the blood pressure before awakening, and after arousal there is a rise in blood pressure to the peak level of the morning. In this article, we examine the effect of a variety of antihypertensive agents on this rhythm. In general, β-adrenoceptor blockers appear to have less effect on nocturnal blood pressure and surge in pressure after arousal, while vasodilators, particularly α-adrenoceptor blockers, have a pronounced effect. These findings indicate that the rise in blood pressure before awakening and the rapid rise upon arousal appear to be due to increased α-adrenoceptor activity.     

电磁脉冲对清醒大鼠尾动脉血压的影响

目的:观察电磁脉冲(electromagnetic pulses,EMP)对清醒大鼠动脉血压和心率的影响。方法:适应性血压测量1周后的14只健康成年雄性SD大鼠按体重随机分为假辐照组和辐照组,每组7只,在锥形平板GTEM小室内接受EMP辐照,EMP辐照参数为:场强200 kV/m,脉冲前沿3.5 ns,脉宽14 ns,重复频率1 Hz,辐照后用无创性尾套式血压测量仪测量2 hr至1 wk内大鼠动脉血压和心率变化规律。结果:照后3 d大鼠动脉血压(收缩压、舒张压和平均动脉压)与假辐照组相比下降显著(P0.05),12 h有下降趋势,其他时间未见显著性差异(P0.05);辐照对大鼠心率也无明显影响(P0.05)。结论:EMP辐照可以引起大鼠血压一过性降低;对大鼠心率无明显影响。     

琥珀酸美托洛尔与美托洛尔对慢性充血性心衰患者心功能的影响

目的：探讨琥珀酸美托洛尔缓释片与美托洛尔片对慢性心力衰竭患者的心功能的影响。方法：选取慢性充血性心衰患者182例临床患者资料,排除67例不符合入选标准病例后,按照服用美托洛尔剂型（缓释片、平片）分为两组,两组均为常规利尿剂ACEI等治疗。美托洛尔组患者服用每日服用25mg-50mg的美托洛尔治疗,均分2次服用。琥珀酸美托洛尔组每日服用23．75-95mg琥珀酸美托洛尔缓释片进行治疗。评价治疗前和治疗12个月后的相关指标,包括：一日5次的平均心率（晨起前,8时,12时,16时,夜间休息前共5次平均心率）、LVDd、EF、BUN、Crea。结果：治疗12个月后,两组患者心率均下降．琥珀酸美托洛尔组与美托洛尔组相比下降更明显（64．0±5．4VS69．5±7．6,P〈0．05）、LVDd、EF、BUN、Crea等指标在两组之间没有差别。结论：慢性充血性心衰患者应用琥珀酸美托洛尔较美托洛尔平片相比可明显降低平均心率。但对于心功能肾功能的影响。琥珀酸关托洛尔较美托洛尔平片相比无明显差异。     

Circadian Pattern of Ambulatory Blood Pressure in Hypertensive Patients With and Without Type 2 Diabetes

There is strong association between diabetes and increased risk of end-organ damage, stroke, and cardiovascular disease (CVD) morbidity and mortality. Non-dipping (<10% decline in the asleep relative to awake blood pressure [BP] mean), as determined by ambulatory BP monitoring (ABPM), is frequent in diabetes and consistently associated with increased CVD risk. The reported prevalence of non-dipping in diabetes is highly variable, probably due to differences in the study groups (normotensive subjects, untreated hypertensives, treated hypertensives), relatively small sample sizes, reliance only on a single, low-reproducibility, 24-h ABPM evaluation per participant, and definition of daytime and nighttime periods by arbitrary selected fixed clock-hour spans. Accordingly, we evaluated the influence of diabetes on the circadian BP pattern by 48-h ABPM (rather than for 24?h to increase reproducibility of results) during which participants maintained a diary listing times of going to bed at night and awakening in the morning. This cross-sectional study involved 12 765 hypertensive patients (6797 men/5968 women), 58.1?±?14.1 (mean?±?SD) yrs of age, enrolled in the Hygia Project, designed to evaluate prospectively CVD risk by ABPM in primary care centers of northwest Spain. Among the participants, 2954 (1799 men/1155 women) had type 2 diabetes. At the time of study, 525/3314 patients with/without diabetes were untreated for hypertension, and the remaining 2429/6497 patients with/without diabetes were treated. Hypertension was defined as awake systolic (SBP)/diastolic (DBP) BP mean ≥135/85?mm Hg, or asleep SBP/DBP mean ≥120/70?mm Hg, or BP-lowering treatment. Hypertensive patients with than without diabetes were more likely to be men and of older age, have diagnoses of microalbuminuria, proteinuria, chronic kidney disease, obstructive sleep apnea, metabolic syndrome, and/or obesity, plus higher glucose, creatinine, uric acid, and triglycerides, but lower cholesterol and estimated glomerular filtration rate. In patients with diabetes, ambulatory SBP was significantly elevated (p?<?.001), mainly during the hours of nighttime sleep and initial hours after morning awakening, independent of presence/absence of BP-lowering treatment. Ambulatory DBP, however, was significantly higher (p?<?.001) in patients without diabetes, mainly during the daytime. Differing trends for SBP and DBP between groups resulted in large differences in ambulatory pulse pressure (PP), it being significantly greater (p?<?.001) throughout the entire 24?h in patients with diabetes, even after correcting for age. Prevalence of non-dipping was significantly higher in patients with than without diabetes (62.1% vs. 45.9%; p?<?.001). Largest difference between groups was in the prevalence of the riser BP pattern, i.e., asleep SBP mean greater than awake SBP mean (19.9% vs. 8.1% in patients with and without diabetes, respectively; p?<?.001). Elevated asleep SBP mean was the major basis for the diagnosis of hypertension and/or inadequate BP control among patients with diabetes; thus, among the uncontrolled hypertensive patients with diabetes, 89.2% had nocturnal hypertension. Our findings document significantly elevated prevalence of a blunted nocturnal BP decline in hypertensive patients with diabetes. Most important, prevalence of the riser BP pattern, associated with highest CVD risk among all possible BP patterns, was more than twice as prevalent in diabetes. Patients with diabetes also presented significantly elevated ambulatory PP, reflecting increased arterial stiffness and enhanced CVD risk. These collective findings indicate that diabetes should be included among the clinical conditions for which ABPM is recommended for proper CVD risk assessment. (Author correspondence: rhermida@uvigo.es)     

改良大鼠左心室插管术及心衰大鼠左心功能指标的测定

目的完善大鼠左心室插管技术并确定充血性心力衰竭（CHF）大鼠心功能指标参数。方法将80只成年雄性SD大鼠随机分为2组：假手术组（SH）,腹主动脉缩窄模型组（CAA）。采用腹主动脉部分缩窄法制作CHF大鼠模型,BL-420E＋生物信号采集系统测定心功能参数。观察比较2组大鼠第6周后测定的心功能的各项指标。结果（1）经进一步完善大鼠左心室插管技术,成功率明显提高。（2）CAA组大鼠心功能明显减低,左室重量指数（LVMI）、左室舒张末压（LVEDP）升高,左心室内压上升、下降的最大变化速率（±dp/dtmax）下降（P〈0.01）。结论改良大鼠左心室插管术提高成功率,心衰大鼠的心功能指标明显改变。     

Temporal (Circadian) and Functional Relationship Between Atrial Natriuretic Peptides and Blood Pressure

Long-acting natriuretic peptide, vessel dilator, and atrial natriuretic factor consisting of amino acids (a.a.) 1 to 30, 31 to 67, and 99 to 126 of the 126-a.a. atrial natriuretic factor (ANF) prohormone, respectively, circulate in humans and have potent vasodilatory properties. To determine if these atrial natriuretic peptides are directly related to blood pressure in clinically healthy normotensive humans, we obtained 24-h profiles of vessel dilator, long-acting natriuretic peptide, ANF, and blood pressure in 10 men in 1988 and 11 men in 1993 (seven men were studied twice) to compare circulating concentrations of atrial natriuretic peptides with naturally occurring changes in blood pressure. Overall, vessel dilator, long-acting natriuretic peptide, and ANF each had significant (p > 0.001) circadian rhythms, with peak concentrations late during sleep (at 04:00 h) being nearly twice their concentrations in the afternoon and evening. This high-amplitude circadian change allowed for the refinement of normal limits for ANF peptides by computing 3-hourly tolerance intervals (chronodesms) against which to compare time-specified single samples for normality. Systolic, diastolic, and mean arterial blood pressure also had significant circadian rhythms (p > 0.001) with peaks and troughs that were exactly opposite those of the ANF peptides. In addition to this inverse temporal relationship, there was a significant inverse correlation between absolute values for blood pressure and each ANF peptide (p > 0.001), implying a functional relationship. These data suggest that in addition to other well-established neurochemical factors, the ANF peptides (vessel dilator, long-acting natriuretic peptide, and ANF) are important for the maintenance of blood pressure and modulation of its circadian rhythm.     

Circadian Time-Qualified Tolerance Intervals for Ambulatory Blood Pressure Monitoring in the Diagnosis of Hypertension

The large-amplitude circadian pattern in blood pressure of healthy subjects of both genders suggests that the constant threshold currently used to diagnose hypertension should be replaced by a time-specified reference limit reflecting the mostly predictable blood pressure variability during the 24 h. Accordingly, we derived circadian time-specified reference standards for blood pressure as a function of gender. We studied 743 normotensive Caucasian volunteers (400 men and 343 women), 45.7 ± 16.5 (mean ± SD) years of age. Blood pressure was measured by ambulatory monitoring at 20-min intervals during the day and at 30-min intervals at night for 48 consecutive hours. Data from each blood pressure series were synchronized according to the rest-activity cycle of each individual in order to avoid differences among subjects in actual times of daily activity. Data were then used to compute 90% circadian tolerance intervals for each gender separately. The method, derived on the basis of bootstrap techniques, does not need to assume normality or symmetry in the data and, therefore, it is highly appropriate to describe the circadian pattern of blood pressure variability. Results reflect expected changes in the tolerance limits as a function of gender and circadian sampling time, as well as upper blood pressure limits below the thresholds currently used for diagnosing hypertension, especially for women. The use of these time-dependent tolerance limits for the computation of a hyperbaric index as a measure of blood pressure excess has already been shown to provide a reproducible and high-sensitivity test for the diagnosis of hypertension, which can also be used to evaluate treatment efficacy.     

Blood Pressure Circadian Rhythm and Variability in Essential Hypertensives without End-organ Damage

The aim of the study was to evaluate the 24-hour Blood Pressure (BP) profile in essential hypertensives without end-organ damage using a two-step method proposed by Staessen and his group: the existence of a circadian rhythm is first tested using Siegel’s Runs-Test, then a Fourier multiple harmonic analysis allows an adequate parametrical representation of the 24-hour BP profile. Sixty-five newly diagnosed, untreated mild-to-moderate essential hypertensives without end-organ damage (HYP) were compared to 29 normal control subjects (NORM). No significant differences have been found between the two groups when considering the existence of a BP circadian rhythm and acrophase parameters, as distinct from amplitudes (p&lt;0.01). Furthermore, as expected, BP mean values were found higher in the HYP group as compared with the NORM group. In conclusion, according to our results, essential hypertensives without end-organ damage present a preserved BP profile, showing a circadian rhythm, but, as compared to normal subjects, increased BP variability (BPV) as expressed by amplitude values. The present study is consistent with the hypothesis that BPV, even though related, is not a consequence of end-organ damage.     

Synchronization of the Circadian Activity Rhythm in Hamsters Following Intermittent Schedule Shifts

The time course of resynchronization of the circadian activity rhythm of hamsters was observed following a 10-hr advance or delay in the light-dark cycle (LD 12:12). Twenty-six shift patterns of the lighting schedule were studied; they consisted of continuous (daily), three-step, two-step and one-step shifting. So long as the daily shift of the lighting schedule was 1 hr or less, the locomotor rhythm followed the continuous shift perfectly. As the amount of daily shift increased, the time course of activity onset deviated more from the time of lights off; the tendency was more marked in advancing than in delaying shifts. Responses of the activity rhythm to stepwise shifting were essentially the same as those to a continuous shift. They were, however, characterized by larger individual variations, and it took additional days before entrainment was achieved. By fitting the time course of entrainment to an exponential model with a constant term, estimates of time constant and shift error were derived. The time constant became shorter with increasing amounts of daily shifts up to 2 hr per day, increasing the number of shift steps, and/or reducing the amount of the initial shift of the seies. The shift error estimated was 0.51 ± 0.12 hr, indicating precise resynchronization. Accordingly, a quicker resynchronization may be expected when a multiple step shift with a moderate initial shift are employed. In the case of a 10-hr shift, for example, a shift of 3 hr followed by another 7 hr may be recommended.