Molecular Mechanisms Underlying the Circadian Rhythm of Blood Pressure in Normotensive Subjects
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BLOOD PRESSURE MONITORING AND MANAGEMENT (J COCKCROFT, SECTION EDITOR)
Molecular Mechanisms Underlying the Circadian Rhythm of Blood Pressure in Normotensive Subjects Yves Lecarpentier 1 & Olivier Schussler 2,3 & Jean-Louis Hébert 4 & Alexandre Vallée 5
# The Author(s) 2020
Abstract Purpose of Review Blood pressure (BP) follows a circadian rhythm (CR) in normotensive subjects. BP increases in the morning and decreases at night. This review aims at providing an up-to-date overview regarding the molecular mechanisms underlying the circadian regulation of BP. Recent Findings The suprachiasmatic nucleus (SCN) is the regulatory center for CRs. In SCN astrocytes, the phosphorylated glycogen synthase kinase-3β (pGSK-3β) also follows a CR and its expression reaches a maximum in the morning and decreases at night. pGSK-3β induces the β-catenin migration to the nucleus. During the daytime, the nuclear β-catenin increases the expression of the glutamate excitatory amino acid transporter 2 (EAAT2) and glutamine synthetase (GS). In SCN, EAAT2 removes glutamate from the synaptic cleft of glutamatergic neurons and transfers it to the astrocyte cytoplasm where GS converts glutamate into glutamine. Thus, glutamate decreases in the synaptic cleft. This decreases the stimulation of the glutamate receptors AMPA-R and NMDA-R located on glutamatergic post-synaptic neurons. Consequently, activation of NTS is decreased and BP increases. The opposite occurs at night. Summary Despite several studies resulting from animal studies, the circadian regulation of BP appears largely controlled in normotensive subjects by the canonical WNT/β-catenin pathway involving the SCN, astrocytes, and glutamatergic neurons. Keywords Arterial blood pressure . Canonical WNT/β-catenin pathway . Glycogen synthase kinase . Astrocyte . Circadian rhythm . Suprachiasmatic nucleus . Glutamine synthetase, nucleus tractus solitarius
Introduction Numerous physiological regulations vary rhythmically over the course of a 24-h day. Circadian rhythms (CRs) such as This article is part of the Topical Collection on Blood Pressure Monitoring and Management * Yves Lecarpentier [email protected] 1
Centre de Recherche Clinique, Grand Hôpital de l’Est Francilien, 77104 Meaux, France
2
Department of Thoracic surgery, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
3
Department of Cardiovascular Surgery, Research Laboratory, Geneva University Hospital, Geneva, Switzerland
4
Cardiology Institute, Pitié-Salpétrière Hospital, AP-HP, Paris, France
5
Diagnosis and Therapeutic Center, Hypertension and Cardiovascular Prevention Unit, Paris-Descartes University, Hôtel-Dieu Hospital, AP-HP, Paris, France
body temperature, sleep-wake cycles, metabolism, and blood pressure (BP) represent various examples of CRs. Although BP is relatively stable over time in normotensive subjects [1], it varies throughout the day, according to a CR [2–4]. Thus, BP starts to rise during the morning (morning surge), about 1 h prior to awakening and decreas
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