Altered Orcadian Rhythms of Blood Pressure and Heart Rate in Non-Hemodialysis Chronic Renal Failure

The extended use of ambulatory monitoring has permitted the identification of many conditions in which the circadian rhythm of blood pressure is altered. The common denominator seems to be an impairment of the autonomic nervous system function. We examined whether the circadian blood pressure rhythm is altered in chronic renal failure (where autonomic dysfunction is usually present) by using a standardized chronobiological inferential statistical method in hospitalized subjects. For this purpose, a group of 30 non-hemodialysis hypertensive patients with chronic renal failure was compared with a second group of 30 patients affected by uncomplicated mild-to-moderate essential hypertension. The two groups were matched by age, sex and circadian mesors of blood pressure. Diet, meal times, sleep and activity logs were standardized. Blood pressure and heart rate recordings were obtained by using an automatic oscillometric recorder and subsequently analyzed according to the cosinor method. A mean circadian rhythm of blood pressure was documented in both groups, but while the mean acrophases occurred between 2 and 3 p.m. in essential hypertension, in renal failure they were between 11 p.m. and midnight for blood pressure and around 7 p.m. for heart rate. In addition, the mean circadian amplitudes were significantly lower in renal failure, while the mean circadian mesor of heart rate was significantly higher. Our data demonstrate that the circadian rhythms of blood pressure and heart rate are altered also in hypertension due to chronic renal failure.     

应用植入式遥测技术观察自发性高血压大鼠血压的昼夜波动

目的应用植入式遥测技术观察自发性高血压大鼠在清醒无束缚状态下血压昼夜波动变化。方法取8只SPF级3月龄雄性SHR大鼠,进行C50-PXT植入子植入手术,恢复7 d后,用遥测系统进行24 h连续清醒无束缚的血压监测,并用EMKA分析软件对动态血压心率均值、24 h血压心率趋势等指标进行分析。结果 3月龄的SHR大鼠血压和心律呈昼夜节律性变化,白昼阶段血压明显低于夜间阶段(P<0.01),血压在1∶30～2∶30和20∶30～21∶30时出现两个高峰期,14∶00～14∶30时出现一低谷期。其中夜间阶段平均收缩压为166.02 mmHg,两个收缩压峰值分别为172.13 mmHg和171.38 mmHg;白昼平均收缩压是162.73 mmHg,收缩压谷底值为155.73mmHg。而心率两个高峰期出现在1∶30～2∶00和20∶00～21∶00,高峰值分别为375.00次/分和373.26次/分;心率低谷出现在11∶00左右,谷底值为310.91次/分,白昼和夜间的平均心率分别为328.85次/分和346.05次/分。结论 3月龄的SHR大鼠血压和心律呈昼夜节律性变化,血压和心率在夜间出现两个高峰,白昼出现一个低谷,且夜间的平均血压和心率要高于白昼,SHR大鼠的血压和心率的节律变化与其活动有关。植入式遥测技术可准确反映SHR大鼠血压昼夜的节律性变化,有助于正确评价抗高血压药物的作用和高血压的生理机制研究。     

Atrial Natriuretic Peptide and Circadian Blood Pressure Regulation: Clues from a Chronobiological Approach

A critical review of the data available in the literature today permits a better understanding of the multiple actions of atrial natriuretic peptide (ANP) on the cardiovascular system. Moreover, the results of chronobiological studies suggest a role for this peptide in the determination of the circadian rhythm of blood pressure (BP). ANP can affect BP by several mechanisms, including modification of renal function and vascular tone, counteraction of the renin-angiotensin-al-dosterone system, and action on brain regulatory sites. A series of interrelated events may follow from very small changes in the plasma levels of ANP. The endpoints are blood volume and BP reduction, but they are rapidly offset (mainly by reactive sympathetic activation) as soon as blood volume or pressure is thredtened. The circadian rhythms of BP and ANP are antiphasic under normal conditions and in essential hypertension. The loss in the nocturnal decrease of BP is accompanied by a comparable loss in the nocturnal surge of ANP in hypertensive renal failure and hypotensive heart failure. In the latter condition, BP and ANP variabilities correlate significantly both before and after therapy-induced functional recovery, independently of the mean BP levels. Autonomic function modulates the secretion of ANP, which seems more apt to determine only transient changes in BP levels, as suggested by the short half-life of the peptide and the buffering role of its clearance receptors. There is now sufficient evidence that ANP contributes to short-term control over BP and electrolyte balance, in contrast and in opposition to the renin-angiotensin-aldosterone system, which is involved primarily in long-term BP control. By interfering with other well-established neu-rohormonal factors, ANP appears to be an additional modulator of the circadian rhythm of BP.     

Endothelin-1 in chronic renal failure and hypertension

Investigation into the role of endothelin-1 (ET-1) in renal function has revealed two major direct actions leading to the control of extracellular volume and blood pressure. These are the regulation of renal hemodynamics and glomerular filtration rate and the modulation of sodium and water excretion. In the rat remnant kidney model of chronic renal failure, ET-1 production is increased in blood vessels and renal tissues. These changes are related to an increase in preproET-1 expression and correlate with the rise in blood pressure, the development of cardiovascular hypertrophy, and the degree of renal insufficiency and injury. Selective ETA receptor blockade prevents the progression of hypertension and the vascular and renal damage, supporting a role for ET-1 in chronic renal failure progression. The increase in ET-1 production can be associated with other local mediators, including angiotensin II, transforming growth factor-beta1 and nitric oxide, the local production of which is also altered in chronic renal failure. In human patients with essential hypertension, atherosclerosis, and nephrosclerosis, plasma ET-1 levels are increased compared with patients with uncomplicated essential hypertension. Similarly, plasma ET-1 concentrations are markedly increased in patients with end-stage renal disease undergoing dialysis, and this correlates with blood pressure, suggesting that ET-1 may contribute to hypertension in these patients. The treatment of anemia in patients with renal failure with human recombinant erythropoietin increases blood pressure by accentuating the underlying endothelial dysfunction and the elevated vascular ET-1 production. Overall, these results support a role for ET-1 in hypertension and the end-organ damage associated with chronic renal failure. ETA receptor blockade may then represent a potential target for the management of hypertension and cardiovascular and renal protection.     

基于遥测技术对巴马小型猪部分生理指标的观测

目的：应用遥测技术观察巴马小型猪在清醒自由状态下心电、血压、呼吸、活动等指标昼夜波动变化。方法取雄性6月龄巴马小型猪6只,行浅表股动脉VAP血管通路植入手术,恢复7 d后,用EMAK遥测系统进行24 h连续清醒自由状态下心电、血压、呼吸、活动指标监测,并用EMAK分析软件对上述指标进行分析。结果6月龄巴马小型猪心电、血压、呼吸、活动都有昼夜节律变化,白昼心率显著高于黑夜心率（ P ＜0.01）,且白昼PR间期、QRS间期与QT间期均显著低于黑夜（P ＜0.05,P ＜0.01）,白昼平均心率为76.22次/分,黑夜平均心率为67.03次/分,白昼平均PR间期、QRS间期和QT间期分别为109.97 ms、42.72 ms、380.37 ms,黑夜平均PR间期、QRS间期和QT间期为112.32 ms、44.01 ms、389.24 ms。巴马小型猪白昼收缩压、舒张压、平均压都显著高于夜间（ P ＜0.01）,白昼平均收缩压、舒张压、平均压分别为129.57 mmHg、96.75 mmHg、111.73 mmHg,夜间平均收缩压、舒张压、平均压分别为122.81 mmHg、92.65 mmHg、106.19 mmHg,且黑夜收缩压、舒张压、平均压下降率分别为19.89％、19.05％、19.35％。另外,巴马小型猪在白昼的活动情况与呼吸频率都要显著高于夜间（ P ＜0.01）。结论利用遥测技术可以对清醒自由状态下巴马小型猪心电、血压、呼吸、活动等进行连续监测,能真实的反应小型猪在24 h内上述生理指标的变化规律,为巴马小型猪在药理毒理研究中的应用提供参考。     

原发性高血压患者血压昼夜节律与靶器官损害的关系研究

目的:研究原发性高血压患者血压昼夜节律异常是否与靶器官损害存在关联。方法:将2015年2~11月份在我院治疗的94例原发性高血压病人按照血压昼夜节律是否正常分为节律正常组52例和异常组42例。比较两组患者的24h、白天、夜间的收缩压(SBP)与舒张压(DBP)及血压负荷,并且比较两组患者心脏、脑、肾损伤相关指标。结果:异常组全天24h、白天、夜间SBP及DBP,血压负荷均高于正常组,差异具有统计学意义(P0.05)。异常组患者左室重量(LVM)和左室重量指数(LVMI)、发生心肌缺血次数及持续时间、发生脑梗死几率均明显高于正常组,差异有统计学意义(P0.05)。异常组尿微量白蛋白(MAU)、尿酸(UA)水平均高于正常组,差异有统计学意义(P0.05)。结论:原发性高血压患者出现昼夜节律异常,可能对相关靶器官造成损伤。     

Chronophysiology of the cardiovascular system

The development of ambulatory blood pressure monitoring devices and the beat-by-beat measurement of heart rate have enabled it to be established that there are circadian rhythms in heart rate and blood pressure in subjects living normally. Investigations of these variables have led to quantification of their fall at night, and rapid rise on awakening and becoming active in the morning. These changes are of particular interest insofar as abnormalities in them are associated with cardiovascular problems and morbidity in patients and also act as risk factors in otherwise healthy individuals. It has also been shown that there are many other variables of the cardiovascular system. The causes of the circadian rhythms in heart rate and blood pressure are outlined, with particular stress upon the role of the autonomic nervous system, as assessed from low- and high-frequency components of the variation in heart rate measured beat-by-beat. Activity increases blood pressure, but there is evidence that this “reactivity” varies with time of day, and this also might be related to cardiovascular morbidity. Based upon data from several sources, including night work, resting subjects and bed-ridden patients, it is concluded that the contribution of the “body clock” to producing the circadian rhythm in heart rate and blood pressure is relatively small. A bias towards an exogenous cause applies also to most other circadian rhythms in the cardiovascular system. Knowledge of circadian rhythmicity in cardiovascular system, together with an understanding of its causes, provides a rationale for advice to reduce cardiovascular risk and to assess the efficacy of therapies.     

24-hour profiles of blood pressure and heart rate in Cushing's syndrome: relationship between cortisol and cardiovascular rhythmicities

We monitored the circadian profiles of cortisol, systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) in 33 matched normotensive subjects, 32 patients with essential hypertension and 16 patients with Cushing's Syndrome (8 pituitary adenomas, 6 adrenal adenomas and 2 adrenal carcinomas). Each subject underwent serial blood drawings at 4-hr intervals along the 24-hr cycle. BP and HR were automatically recorded every 30 min. Data were analyzed by conventional statistics and by chronobiological procedures (cosinor rhythmometry). Both the control subjects and essential hypertensives showed a circadian profile of BP and HR characterized by a peak in the early afternoon and a clear nocturnal fall (rhythm detection: P less than 0.001). The rhythmicity of BP was disrupted in patients affected by Cushing's Syndrome, whereas the 24-hr oscillation of HR was preserved (P less than 0.001). Our data are compatible with the view that glucocorticoids are involved in the control of BP circadian rhythm, whereas HR is not under their control.     

Nighttime Blood Pressure and White Matter Hyperintensities in Patients With Parkinson Disease

Increasing evidence indicates that nocturnal blood pressure level and/or loss of nocturnal blood pressure dips are sensitive markers of cardiovascular morbidity and mortality. Several studies have suggested that blunted heart rate variability and nocturnal decline in heart rate are also associated with target organ damage. These phenomena occur relatively commonly in patients with Parkinson disease (PD); however, few studies have assessed the consequences of these abnormalities in patients with PD. We investigated the influence of circadian changes in blood pressure and heart rate on white matter hyperintensities (WMHs) in patients with PD. The presence of nocturnal hypertension was associated with increased WMH score, and nighttime systolic pressure was closely related with white matter changes. Blunted heart rate variability and nocturnal decline in heart rate were also related to increasing WMH scores. The non-dipping phenomenon did not influence WMHs. These findings suggest that white matter changes are related to circadian autonomic dysfunction, particularly nocturnal hypertension in patients with PD. Therefore, it is important to monitor nocturnal blood pressure status, because modifying these circadian regulatory disturbances can be beneficial to protect against vascular brain damage in patients with PD. (Author correspondence: neuronet@catholic.ac.kr)     

Effects of obstructive sleep apnea on endogenous circadian rhythms assessed during relaxed wakefulness; an exploratory analysis

ABSTRACT

Obstructive sleep apnea (OSA) is associated with hypertension, cardiovascular disease, and a change in the 24 h pattern of adverse cardiovascular events and mortality. Adverse cardiovascular events occur more frequently in the middle of the night in people with OSA, earlier than the morning prevalence of these events in the general population. It is unknown if these changes are associated with a change in the underlying circadian rhythms, independent of behaviors such as sleep, physical activity, and meal intake. In this exploratory analysis, we studied the endogenous circadian rhythms of blood pressure, heart rate, melatonin and cortisol in 11 participants (48 ± 4 years; seven with OSA) throughout a 5 day study that was originally designed to examine circadian characteristics of obstructive apnea events. After a baseline night, participants completed 10 recurring 5 h 20 min behavioral cycles divided evenly into standardized sleep and wake periods. Blood pressure and heart rate were recorded in a relaxed semirecumbent posture 15 minutes after each scheduled wake time. Salivary melatonin and cortisol concentrations were measured at 1–1.5 h intervals during wakefulness. Mixed-model cosinor analyses were performed to determine the rhythmicity of all variables with respect to external time and separately to circadian phases (aligned to the dim light melatonin onset, DLMO). The circadian rhythm of blood pressure peaked much later in OSA compared to control participants (group × circadian phase, p < .05); there was also a trend toward a slightly delayed cortisol rhythm in the OSA group. Rhythms of heart rate and melatonin did not differ between the groups. In this exploratory analysis, OSA appears to be associated with a phase change (relative to DLMO) in the endogenous circadian rhythm of blood pressure during relaxed wakefulness, independent of common daily behaviors.     

Circadian rhythm of blood pressure in congestive heart failure and effects of ACE inhibitors.

In 33 patients with heart failure (NYHA II-III), the 24-h blood pressure rhythm was examined before and after the titration period of two ACE inhibitors. Blood pressure was measured by the oscillometric method using the blood pressure monitor 90202 from SpaceLabs, Inc. The measurements were taken from 06:00 to 22:00 h every 20 min and from 22:00 to 06:00 h every hour. Patients were randomized to therapy with either captopril (group 1, n = 17) or enalapril (group 2, n = 16). The average daily dosage of captopril was 41 +/- 3 mg given in three divided doses (08:00, 12:00, and 17:00 h). The mean dose of enalapril was 8 +/- 1 mg once daily (08:00 h). Serum electrolytes, serum creatinine, and plasma renin activity were measured before and during therapy with both ACE inhibitors. Twenty-four-hour blood pressure measurements were taken before and on the fifth day of treatment with ACE inhibitors. Both groups were not different with respect to the degree of heart failure, the concomitant medication, and the 24-h profiles of blood pressure and heart rate before initiation of ACE inhibition. The 24-h blood pressure values on day 5 were consistently below the pretreatment values (p less than 0.005) in both groups. Both groups did not differ significantly during ACE inhibition in their 24-h blood pressure and heart rate profiles. In both groups, the mesor of the systolic and diastolic blood pressure decreased significantly by the same degree (by 4.7/5.1 mmg Hg in group 1 and 6.4/4.1 mm Hg in group 2). The systolic/diastolic blood pressure amplitude decreased slightly in both groups. Before treatment, serum sodium, potassium, and creatinine were within the normal range. The increase in potassium (0.5 +/- 0.1 mmol/L) reached statistical significance (p less than 0.01) only in the captopril group, whereas it was not significant in the enalapril group (0.1 +/- 0.1 mmol/L). Serum creatinine was not significantly altered by both ACE inhibitors. No relationship could be found between the changes in serum potassium or creatinine and the mean of the 24-h blood pressure values during ACE inhibition. Captopril and enalapril showed comparable blood pressure profiles and similar effects on renal function at the end of the titration on day 5. It can therefore be concluded that the effects on blood pressure rhythm and renal function are similar with a single daily dose of enalapril compared to captopril given three times daily.     

24-Hour Profiles of Blood Pressure and Heart Rate in Cushing's Syndrome: Relationship Between Cortisol and Cardiovascular Rhythmicities

We monitored the circadian profiles of Cortisol, systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) in 33 matched normotensive subjects, 32 patients with essential hypertension and 16 patients with Cushing's Syndrome (8 pituitary adenomas, 6 adrenal adenomas and 2 adrenal carcinomas). Each subject underwent serial blood drawings at 4-hr intervals along the 24-hr cycle. BP and HR were automatically recorded every 30 min. Data were analyzed by conventional statistics and by chronobiological procedures (cosinor rhythmometry). Both the control subjects and essential hypertensives showed a circadian profile of BP and HR characterized by a peak in the early afternoon and a clear nocturnal fall (rhythm detection: P< 0.001). The rhythmicity of BP was disrupted in patients affected by Cushing's Syndrome, whereas the 24-hr oscillation of HR was preserved (P < 0.001). Our data are compatible with the view that glucocorticoids are involved in the control of BP circadian rhythm, whereas HR is not under their control.     

Circadian variations of catecholamines and blood pressure in patients with pseudohypoparathyroidism and hypertension

The relationship between 24-h recumbent blood pressure levels and secretory patterns of catecholamines was investigated in 4 patients with pseudohypoparathyroidism (PsHP) and hypertension and in 9 patients with essential hypertension. A clear circadian rhythm of blood pressure and catecholamines was documented in both groups with lowest levels of blood pressures and catecholamines occurring during sleep. During the 24-h period of recumbency mean arterial blood pressure (MAP) was correlated (r = 0.63, p less than or equal to 0.01) with plasma norepinephrine (N) in the patients with essential hypertension, but this correlation was weaker in patients with PsHP (r = 0.38, p less than or equal to 0.05). MAP was more closely related to plasma epinephrine (E) (r = 0.62, p less than or equal to 0.01) than to plasma NE in patients with PsHP. Plasma NE and E levels were considerably lower in patients with PsHP than in patients with essential hypertension throughout the 24-h recumbent period. The sleep-related decline in blood pressure and NE was less than in patients with essential hypertension. These results suggest that while the sympathetic nervous system may have a role in hour-to-hour maintenance of blood pressure in patients with PsHP and hypertension, it does not appear to be responsible for the elevated arterial pressure in these patients. Factors other than those investigated, such as obesity, alterations in sodium homeostasis of refractoriness of the vascular smooth muscle to the vasodilatory effect of PTH may be involved in the pathogenesis of hypertension in PsHP.     

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 08:00 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 II, and 81.5 +/- 12 pmol/L in the group of 10 patients in class III-IV. In normal subjects, plasma ANP concentration was highest at 04:00 h (21.5 +/- 2.7 pmol/L) and lowest at 16:00 h (8.8 +/- 2.4 pmol/L; p less than 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.     

Blood level of free serotonin, catecholamines and the renin-angiotensin-aldosterone system in patients with primary hypertension]

Two subgroups of patients were selected out of those dialysed for chronic renal failure. Group A included patients without arterial hypertension before dialysis, and group B patients with arterial hypertension before dialysis. Blood endogenous digoxin-like substance (DLS) has been assayed. Its blood levels were not increased in hypertensive patients either before or after dialysis. No correlation was found between DLS and mean arterial pressure in the whole group of patients with chronic renal failure. The obtained results do not suggest that arterial blood pressure in patients with chronic renal failure is related to the presence of DLS in the blood.     

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 and Short-Term Regulation of Blood Pressure and Heart Rate in Transgenic Mice with Cardiac Overexpression of The β1-Adrenoceptor

Congestive heart failure is associated with a loss of circadian and short-term variability in blood pressure and heart rate. In order to assess the contribution of elevated cardiac sympathetic activity to the disturbed cardiovascular regulation, we monitored blood pressure and heart rate in mice with cardiac overexpression of the β₁-adrenoceptor prior to the development of overt heart failure. Telemetry transmitters for continuous monitoring of blood pressure and heart rate were implanted in 8 to 9-week-old wildtype and transgenic mice, derived from crosses of heterozygous transgenic (line β₁TG4) and wildtype mice. Cardiovascular circadian patterns were analyzed under baseline conditions and during treatment with propranolol (500 mg/L in drinking water). Short-term variability was assessed by spectral analysis of beat-to-beat data sampled for 30 min at four circadian times. Transgenic β₁TG4 mice showed an increase in 24 h heart rate, while blood pressure was not different from wildtype controls. Circadian patterns in blood pressure and heart were preserved in β₁TG4 mice. Addition of propranolol to the animals’ drinking water led to a reduction in heart rate and its 24 h variation in both strains of mice. Short-term variability in blood pressure was not different between wildtype and β₁TG4 mice, but heart rate variability in the transgenic animals showed a rightward shift of the high-frequency component in the nocturnal activity period, suggesting an increase in respiratory frequency. In conclusion, the present study shows that both the circadian and the short-term regulation of blood pressure and heart rate are largely preserved in young, nonfailing β₁-transgenic mice. This finding suggests that the loss of blood pressure and heart rate variability observed in human congestive heart failure cannot be attributed solely to sympathetic overactivity but reflects the loss of adrenergic responsiveness to changes in the activity of the autonomic nervous system.     

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 Rhythm of Blood Pressure in Congestive Heart Failure and Effects of ACE Inhibitors

In 33 patients with heart failure (NYHA 11-III), the 24-h blood pressure rhythm was examined before and after the titration period of two ACE inhibitors. Blood pressure was measured by the oscillometric method using the blood pressure monitor 90202 from SpaceLabs, Inc. The measurements were taken from 06:OO to 22:OO h every 20 min and from 22:00 to 06:00 h every hour. Patients were randomized to therapy with either captopril (group 1, n = 17) or enalapril (group 2, n = 16). The average daily dosage of captopril was 41 ± 3 mg given in three divided doses (08:00, 12:00, and 17:00 h). The mean dose of enalapril was 8 ± 1 mg once daily (08:00 h). Serum electrolytes, serum creatinine, and plasma renin activity were measured before and during therapy with both ACE inhibitors. Twenty-four-hour blood pressure measurements were taken before and on the fifth day of treatment with ACE inhibitors. Both groups were not different with respect to the degree of heart failure, the concomitant medication, and the 24-h profiles of blood pressure and heart rate before initiation of ACE inhibition. The 24-h blood pressure values on day 5 were consistently below the pretreatment values (p < 0.005) in both groups. Both groups did not differ significantly during ACE inhibition in their 24-h blood pressure and heart rate profiles. In both groups, the mesor of the systolic and diastolic blood pressure decreased significantly by the same degree (by 4.7/5.1 mmg Hg in group 1 and 6.4/4.1 mm Hg in group 2). The systolic/diastolic blood pressure amplitude decreased slightly in both groups. Before treatment, serum sodium, potassium, and creatinine were within the normal range. The increase in potassium (0.5 ± 0.1 mmol/L) reached statistical significance (p < 0.01) only in the captopril group, whereas it was not significant in the enalapril group (0.1 ± 0.1 mmol/L). Serum creatinine was not significantly altered by both ACE inhibitors. No relationship could be found between the changes in serum potassium or creatinine and the mean of the 24-h blood pressure values during ACE inhibition. Captopril and enalapril showed comparable blood pressure profiles and similar effects on renal function at the end of the titration on day 5. It can therefore be concluded that the effects on blood pressure rhythm and renal function are similar with a single daily dose of enalapril compared to captopril given three times daily.     

Circadian and short-term regulation of blood pressure and heart rate in transgenic mice with cardiac overexpression of the beta1-adrenoceptor

Congestive heart failure is associated with a loss of circadian and short-term variability in blood pressure and heart rate. In order to assess the contribution of elevated cardiac sympathetic activity to the disturbed cardiovascular regulation, we monitored blood pressure and heart rate in mice with cardiac overexpression of the β₁-adrenoceptor prior to the development of overt heart failure. Telemetry transmitters for continuous monitoring of blood pressure and heart rate were implanted in 8 to 9-week-old wildtype and transgenic mice, derived from crosses of heterozygous transgenic (line β₁TG4) and wildtype mice. Cardiovascular circadian patterns were analyzed under baseline conditions and during treatment with propranolol (500 mg/L in drinking water). Short-term variability was assessed by spectral analysis of beat-to-beat data sampled for 30 min at four circadian times. Transgenic β₁TG4 mice showed an increase in 24 h heart rate, while blood pressure was not different from wildtype controls. Circadian patterns in blood pressure and heart were preserved in β₁TG4 mice. Addition of propranolol to the animals' drinking water led to a reduction in heart rate and its 24 h variation in both strains of mice. Short-term variability in blood pressure was not different between wildtype and β₁TG4 mice, but heart rate variability in the transgenic animals showed a rightward shift of the high-frequency component in the nocturnal activity period, suggesting an increase in respiratory frequency. In conclusion, the present study shows that both the circadian and the short-term regulation of blood pressure and heart rate are largely preserved in young, nonfailing β₁-transgenic mice. This finding suggests that the loss of blood pressure and heart rate variability observed in human congestive heart failure cannot be attributed solely to sympathetic overactivity but reflects the loss of adrenergic responsiveness to changes in the activity of the autonomic nervous system.