Cited by 237Blood Pressure and Hypertension StudiesCircadian rhythm and melatoninHeart Rate Variability and Autonomic Control

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Circadian mechanisms of 24-hour blood pressure regulation and patterning

Smolensky, Michael H., Hermida, Ramón C., Portaluppi, Francesco·2017·Sleep Medicine Reviews

DOI 10.1016/j.smrv.2016.02.003

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Abstract

In most persons, blood pressure (BP) rises slowly during late sleep, increases rapidly upon morning awakening and commencement of diurnal activity, exhibits two - morning and afternoon/early evening - daytime peaks, shows a minor midday nadir, and undergoes a decline during nighttime sleep by 10-20% in systolic BP and somewhat lesser amount in diastolic BP relative to wake-time means. Nyctohemeral cycles of ambient temperature, light, noise and behaviorally driven temporal patterns in food, liquid, salt, and stimulant consumption, mental/emotional stress, posture, and physical activity intensity plus circadian rhythms of wake/sleep, pineal gland melatonin synthesis, autonomic and central nervous, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, renin-angiotensin-aldosterone, renal hemodynamic, endothelial, vasoactive peptide, and opioid systems constitute the key regulators and determinants of the BP 24 h profile. Environmental and behavioral cycles are believed to be far more influential than circadian ones. However, the facts that the: i) BP 24 h pattern of secondary hypertension, e.g., diabetes and renal disease, is characterized by absence of BP fall during sleep, and ii) scheduling of conventional long-acting medications at bedtime, rather than morning, results in much better hypertension control and vascular risk reduction, presumably because highest drug concentration coincides closely with the peak of most key circadian determinants of the BP 24 h profile, indicate endogenous rhythmic influences are of greater importance than previously appreciated.

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Valsartan chronotherapy reverts the non-dipper pattern and improves blood pressure control through mediation of circadian rhythms of the renin-angiotensin system in spontaneous hypertension rats
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“A number of studies have shown components of the RAS system exhibit variations in circadian rhythm (Naito et al. 2014, 2009; Smolensky et al. 2017).”
Background
Prenatal hypoxia increases blood pressure in male rat offspring and affects their response to artificial light at night
Šutovská, H. M., Molčan, Ľ., Koprdová, R., Piešová, M., Mach, M., & Zeman, M. (2020) · Journal of Developmental Origins of Health and Disease · doi:10.1017/s2040174420000963 · Cited by 18
Circadian rhythm in prostate cancer: time to take notice of the clock
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Bedtime Chronotherapy with Conventional Hypertension Medications to Target Increased Asleep Blood Pressure Results in Markedly Better Chronoprevention of Cardiovascular and Other Risks than Customary On-awakening Therapy
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Aging and circadian dysfunction increase alcohol sensitivity and exacerbate mortality in Drosophila melanogaster
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The human circadian clock from health to economics
Koritala, B. S. C., & Çakmaklı, S. (2018) · PsyCh Journal · doi:10.1002/pchj.252 · Cited by 16
Does Timing of Antihypertensive Medication Dosing Matter?
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New perspectives on the definition, diagnosis, and treatment of true arterial hypertension
Hermida, R. C., Smolensky, M. H., Mojón, A., Crespo, J. J., Ríos, M. T. P., Domínguez-Sardiña, M., Otero, A., & Fernández, J. R. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2020.1746274 · Cited by 17
“[9,12,13,15,17,18]; (ii) elevation of atrial natriuretic and calcitonin gene-related vasoactive peptides and nitric oxide as vasodilators [18,87]; and (iii) cardiac remodeling [88–90].”
BackgroundSelf-citation
Blood pressure dipping during REM and non-REM sleep in patients with moderate to severe obstructive sleep apnea
BaHammam, A. S., Alshahrani, M. M., Aleissi, S. A., Olaish, A. H., Alhassoon, M. H., & Shukr, A. (2021) · Scientific Reports · doi:10.1038/s41598-021-87200-3 · Cited by 16
The Correlation Between ABPM Parameters and Left Ventricular Hypertrophy in Pediatric Essential Hypertension
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“● While in some HD patients BP follows this pattern in the interdialytic period, a high proportion of non-dipping (decreased night-time dip) has been reported.”
Background
Circadian rhythm of plasminogen activator inhibitor-1 and cardiovascular complications in type 2 diabetes
Yu, Y., Li, W., Xu, L., & Wang, Y. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1124353 · Cited by 16
“Almost all variables related to the cardiovascular system have a day/night pattern or circadian rhythms (32, 33), including the heart rate (34), blood pressure (34, 35), circulating catecholamines (36, 37), and vascular endothelial function (38).”
Background
Ethnic Differences in Nighttime Melatonin and Nighttime Blood Pressure: A Study in European Americans and African Americans
Jeong, J., Zhu, H., Harris, R. A., Dong, Y., Su, S., Tingen, M. S., Kapuku, G. K., Pollock, J. S., Pollock, D. M., Harshfield, G. A., et al. (2019) · American Journal of Hypertension · doi:10.1093/ajh/hpz083 · Cited by 16
Neurobiology of the circadian clock and its role in cardiovascular disease: Mechanisms, biomarkers, and chronotherapy
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“For instance, blood pressure typically dips during sleep and rises in the early morning, a pattern regulated by the interplay between the SCN and peripheral clocks in the cardiovascular system (CVS) (Douma and Gumz, 2018; Smolensky et al., 2017; Faraci and Scheer, 2024; Hermida et al., 2011).”
Elevated asleep blood pressure and non-dipper 24h patterning best predict risk for heart failure that can be averted by bedtime hypertension chronotherapy: A review of the published literature
Hermida, R. C., Mojón, A., Fernández, J. R., Hermida‐Ayala, R. G., Crespo, J. J., Ríos, M. T. P., Domínguez-Sardiña, M., Otero, A., & Smolensky, M. H. (2021) · Chronobiology International · doi:10.1080/07420528.2021.1939367 · Cited by 15
“…in enhanced protection against the deleterious cardiac, endothelial, and other tissue remodeling, pathology, and injury, which at this specific circadian time is considered to be of greatest risk (Fabbian et al. 2013; Hermida et al. 2017; Portaluppi et al. 2012; Smolensky et al. 2007, 2017).”
BackgroundInfluentialSelf-citation
Circadian desynchronization in pregnancy of Golden hamster following long time light exposure: Involvement of Akt/FoxO1 pathway
Das, M., Mohanty, S. R., Minocha, T., Mishra, N. K., Yadav, S. K., & Haldar, C. (2022) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2022.112508 · Cited by 15
Do night and around-the-clock firefighters’ shift schedules induce deviation in tau from 24 hours of systolic and diastolic blood pressure circadian rhythms?
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“…to the low-amplitude first harmonic contribution to the 24h fundamental τ that comprises the usual multiplecomponent (12h + 24h) waveform of the circadian SBP and DBP pattern of healthy diurnally active persons (but not abnormal sleep-time non-dipper or riser types: see Smolensky et al., 2017).”
BackgroundInfluentialSelf-citation
Night-Time Non-dipping Blood Pressure and Heart Rate: An Association With the Risk of Silent Small Vessel Disease in Patients Presenting With Acute Ischemic Stroke
Akhtar, N., Al-Jerdi, S., Kamran, S., Singh, R., Babu, B. M., Abdelmoneim, M. S., Morgan, D., Joseph, S., Francis, R., & Shuaib, A. M. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.719311 · Cited by 15
“A similar methodology has been used in previous studies (2).”
BackgroundMethodInfluential
The Circadian Rhythm of Thermoregulation Modulates both the Sleep/Wake Cycle and 24 h Pattern of Arterial Blood Pressure
Haghayegh, S., Smolensky, M. H., Khoshnevis, S., Hermida, R. C., Castriotta, R. J., & Diller, K. R. (2021) · Comprehensive physiology · doi:10.1002/cphy.c210008 · Cited by 16
“…other pathologies associated with abnormal asleep ABP (60, 62, 63, 70–72, The ABP 24 h pattern is perceived as the cumulative effects not only of behavioral and environmental cycles but several high-amplitude circadian rhythms, with those of the RAAS and ANS being the most impactful (37, 97, 117).”
InfluentialSelf-citation
Circadian rhythm disruptions: A possible link of bipolar disorder and endocrine comorbidities
Xiu, Y., Xu, P., & Sun, X. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.1065754 · Cited by 14
Circadian rhythm in cardiovascular diseases: a bibliometric analysis of the past, present, and future
Chai, R., Ye, Z., Wu, Q., Xue, W., Shi, S., Du, Y., Wu, H., Yi, W., & Hu, Y. (2023) · European journal of medical research · doi:10.1186/s40001-023-01158-8 · Cited by 15
“In addition, the circadian rhythm is recognized to affect several cardiovascular events, including endothelial function [21–23], thrombus formation [24, 25], blood pressure [26, 27], and heart rate [28].”
Background
Influence of acute dietary nitrate supplementation timing on nitrate metabolism, central and peripheral blood pressure and exercise tolerance in young men
Rowland, S. N., James, L. J., O’Donnell, E., & Bailey, S. J. (2023) · European Journal of Applied Physiology · doi:10.1007/s00421-023-05369-z · Cited by 15
“The factors that regulate BP across the day are multifaceted (including but not limited to renal haemo-dynamics, the nervous system and mental/emotional stress) and highly complex (Smolensky et al. 2017), and as such it is unclear why reductions in brachial BP were not observed in the present study.”
Background
Evening versus morning dosing regimen drug therapy for hypertension
Wu, C., Zhao, P., Xu, P., Wan, C., Singh, S., Varthya, S. B., & Luo, S. (2024) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004184.pub3 · Cited by 14
Association Between Na, K, and Lipid Intake in Each Meal and Blood Pressure
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The influence of external stressors on physiological testing: Implication for return-to-play protocols
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Microsurgical Performance After Sleep Interruption: A NeuroTouch Simulator Study
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Systematic review and quality evaluation of published human ingestion-time trials of blood pressure-lowering medications and their combinations
Hermida, R. C., Hermida‐Ayala, R. G., Mojón, A., Smolensky, M. H., & Fernández, J. R. (2021) · Chronobiology International · doi:10.1080/07420528.2021.1931280 · Cited by 14
“…circadian mechanisms of BP regulation is linked to the state or specific stages of sleep, especially those of the RAAS and ANS (associated with rapid eyeball movement) (Smolensky et al. 2017) that coincide in time with the greatest cardiac remodeling (Martino et al. 2011; Sole and Martino 2009).”
BackgroundInfluentialSelf-citation
Sleep and Circadian Regulation of the Autonomic Nervous System
de Zambotti, M., & Baker, F. C. (2021) · Springer eBooks · doi:10.1007/978-3-030-62263-3_7 · Cited by 13
Dosing time optimization of antihypertensive medications by including the circadian rhythm in pharmacokinetic-pharmacodynamic models
Cortés‐Ríos, J., Hermida, R. C., & Rodriguez-Fernández, M. (2022) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1010711 · Cited by 13
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Understanding the dosing-time-dependent antihypertensive effect of valsartan and aspirin through mathematical modeling
Cortés‐Ríos, J., & Rodriguez-Fernández, M. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1110459 · Cited by 13
“On the other hand, pharmacodynamic changes are due to circadian changes in physiological regulation mechanisms of BP, such as components of the renin-angiotensin-aldosterone system, norepinephrine, epinephrine, Na+ transporters, among others (13, 14), and changes in variables related to routine, such as physical activ…”
Background
A Potential Nontraditional Approach To Combat tmexCD1-toprJ1- Mediated Tigecycline Resistance: Melatonin as a Synergistic Adjuvant of Tigecycline
Wang, X., Liu, T., Lv, X., Sun, N., Li, F., Luo, L., Zhuge, X., Huang, J., & Wang, L. (2023) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00047-23 · Cited by 13
Chronotherapy of hypertension: advantages of 48-h ambulatory blood pressure monitoring assessments in MAPEC and Hygia Chronotherapy Trial
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Self-citation
Bedtime hypertension chronotherapy best reduces cardiovascular disease risk as documented by MAPEC and Hygia Chronotherapy outcomes trials
Hermida, R. C., Mojón, A., & Fernández, J. R. (2020) · Chronobiology International · doi:10.1080/07420528.2020.1771354 · Cited by 13
Self-citation
Circadian rhythm disorder: a potential inducer of vascular calcification?
Huang, H., Li, Z., Ruan, Y., Feng, W., Chen, J., Li, X., Ouyang, L., & Huang, H. (2020) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-020-00767-9 · Cited by 13
Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension—Pro Side of the Argument
Hermida, R. C., Mojón, A., Smolensky, M. H., & Fernández, J. R. (2021) · Hypertension · doi:10.1161/hypertensionaha.120.16500 · Cited by 15
Self-citation
Preclinical evaluation of circadian rhythm in ischemic stroke outcomes.
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Sleep and Cardiovascular Health
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“15 – 17 The autonomic nervous system plays a pivotal role in orchestrating cardiovascular functions during sleep.”
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Chrono‐nutrition for hypertension
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“39 In addition, inappropriate regulation of renal sodium transporters and channels by the circadian clock also results in abnormal sodium handling and BP 47,48 (Figure 3).”
Background
Prognostic utility of rhythmic components in 24-h ambulatory blood pressure monitoring for the risk stratification of chronic kidney disease patients with cardiovascular co-morbidity
Jamal, N. E., Brooks, T. G., Cohen, J. B., Townsend, R. R., Sosa, N., Shah, V. O., Nelson, R. G., Drawz, P. E., Rao, P. S., Bhat, Z. Y., et al. (2024) · Journal of Human Hypertension · doi:10.1038/s41371-023-00884-0 · Cited by 10
“This was neither seen in 24 h blood pressure control (17.20 [13.07 – 22.63] per 1000 person years in uncontrolled BP, 9.85 [5.83 – 22.63] per 1000 person years in controlled BP, p = 057) nor in dipping category (16.11 [12.03 – 21.58] per 1000 person years in non-dippers, 12.55 [8.10 – 19.45] per…”
BackgroundInfluential
Effects of aerobic exercise on ambulatory blood pressure responses to acute partial sleep deprivation: impact of chronotype and sleep quality
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Cycles, Arrows and Turbulence: Time Patterns in Renal Disease, a Path from Epidemiology to Personalized Medicine?
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Assessment of cardiovascular functioning following sport-related concussion: A physiological perspective
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“Furthermore, the ANS exhibits rhythmic circadian changes throughout the day (Smolensky et al., 2017), highlighting the importance of conducting subsequent assessments at the same time of day.”
Background

Authors: Smolensky, M. H., Hermida, R. C., & Portaluppi, F.
Affiliations: The University of Texas at Austin (US)
Universidade de Vigo (ES)
University of Ferrara (IT)
Corresponding author: Smolensky, Michael H.
ORCID: Smolensky, Michael H.
Hermida, Ramón C.
Portaluppi, Francesco
Venue: Sleep Medicine Reviews
Publisher: Elsevier BV
Published: 2017-06
Volume: 33
Pages: 4-16
ISSN: 1087-0792 (ISSN-L)
DOI: 10.1016/j.smrv.2016.02.003
OpenAlex: W2290785732
Cited by: 237
References: 221
Citations by year: 2026: 18 · 2025: 20 · 2024: 33 · 2023: 33 · 2022: 36 · 2021: 32 · 2020: 24 · 2019: 11 · 2018: 12 · 2017: 12
FWCI: 2.42
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Sleep Medicine Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Keywords: circadian rhythm, blood pressure regulation, secondary hypertension, melatonin, renin-angiotensin-aldosterone system, hypothalamic-pituitary-adrenal axis, renal hemodynamics, vasoactive peptides, opioid system, hypertension control
MeSH terms: Antihypertensive Agents, Autonomic Nervous System, Blood Pressure, Circadian Rhythm, Humans, Hypertension, Renin-Angiotensin System, Sleep, Time Factors, Blood Pressure Monitoring, Ambulatory

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Circadian mechanisms of 24-hour blood pressure regulation and patterning

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