Circadian variations in the effects of cardiovascular active drugs
It is now well established that all functions of the cardiovascular system display significant circadian variations (for review see [13–15]). Actually, biological rhythms in heart rate and blood pressure were described at the end of the 18th and the begin
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Zentrum der Pharmakologie, J. W. Goethe-Universitat, Frankfurt, FRG
Introduction It is now well established that all functions of the cardiovascular system display
significant circadian variations (for review see [13 - 15]). Actually, biological rhythms in heart rate and blood pressure were described at the end of the 18 th and the beginning of the 19 th centuries. Falconer in 1797 described periodicities in pulse rate and mentioned that "the pulse, even in the state of perfect health, varies considerably at different times of day" [8]. Similarly, in 180 I, Autenrieth described in his "Handbuch der empirischen menschlichen Physiologie" that the pulse was slower in the morning than in the evening and that daily changes occurred also in body temperature [4]. A daily variability in blood pressure was reported by Zadek in 1881 [35] and by Hill in 1898 [10]. Following these early reports, numerous more sophisticated studies have provided additional convincing evidence for circadian rhythms in heart rate and in systolic and diastolic blood pressure, both in healthy subjects and in patients suffering from cardiovascular diseases (for review see [1317]). Though the rhythms in heart rate and blood pressure are the most well known periodic functions within the cardiovascular system other parameters have been shown to exhibit circadian variations as well (Fig. 1), e.g., in blood flow, stroke volume, capillary resistance, parameters of ECG recordings, in the plasma concentrations of noradrenaline, cAMP (Fig. 2), renin, angiotensin, aldosterone and atrial natriuretic hormone, in blood viscosity and aggregability, etc. (see [13-15]). These findings clearly demonstrate a pronounced rhythmic circadian organization of the cardiovascular system as well as of the mechanisms involved in its regulation. Aside from circadian rhythms in physiological functions of the cardiovascular system, various clinical reports also indicate the onset of cardiovascular diseases, and symptoms exhibit a pronounced temporal dependency (for review see [13-17]). Some representative data are summarized in Fig. 3. It is interesting to note that in patients suffering from angina pectoris ST -segment elevations occur more frequentlyat night ([I], see also Fig. 3), whereas ST-Segment depressions are registered more often during daytime hours [2], indicating differences in etiology. Taking all these data together it is not surprising to note that the effects, as well as the pharmacokinetics of drugs used in the treatment of cardiovascular disorders, were shown to display circadian variations. This will be demonstrated in some representative examples.
T. v. Arnim et al. (eds.), Predisposing Conditions for Acute Ischemic Syndromes © Springer-Verlag Berlin Heidelberg 1989
Variable Heart Morbidity
1229
Heart Mortality
576
Heart Rate
213
PEPI
10
LVETI
10
Cardiac Output
4
Stroke Volume
3
Blood Flow
8
•
.
7
Cap. Resistance Systolic BP
332
Diastolic BP
169
Blood Volume
Fig. 1 Acrophase (time of peak value of rhythm) map in cardiovascular fun
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