Amelioration of the brainstem vascular imbalances in an spontaneously hypertensive rats with exercise

• Grant number: 16/22069-0
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2017
• End date: January 31, 2019
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Thiago dos Santos Moreira
• Grantee: Thiago dos Santos Moreira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The pathophysiology of systemic arterial hypertension is complex and in general poorly understood, but over the last 3 decades studies in animal models and patients with hypertension have provided significant evidence that activation of the sympathetic nervous system is linked to the development and maintenance of the condition. Vasomotor and cardiac activities of spinal sympathetic preganglionic neurons depend on tonic descending excitatory drive generated by sympathoexcitatory (presympathetic) neuronal networks residing in the hypothalamus and the brainstem: the rostral ventrolateral medulla (RVLM), rostral ventromedial and midline medulla, the A5 cell group of the pons, and the paraventricular hypothalamic nucleus. Bulbospinal neurons of the RVLM which belong to the catecholaminergic C1 group are believed to be of a prime importance for the maintenance of vasomotor sympathetic tone.One of the potential mechanisms which may be responsible for sympathetic activation in hypertension is based on the operation of a so-called Cushing response characterized by a triad of high blood pressure, irregular breathing, and bradycardia. Although originally described as an autoresuscitation mechanism recruited under extreme pathological conditions such as brain ischemia, it is currently viewed as a physiological compensatory response to compromised brain perfusion or brain hypoxia. Brainstem vasculature of patients with hypertension and of animal models of hypertension (eg, spontaneously hypertensive rat [SHR]) is considerably narrower (compared with the respective normotensive counterparts), resulting in high cerebral artery resistance. This is not a consequence of hypertension as it occurs prior to its development, at least in the SHR. Thus, the neuronal sympathoexcitatory networks that control the arterial blood pressure have been suggested to be hypoperfused/hypoxic. By increasing systemic arterial blood pressure in response to compromised brainstem perfusion, the Cushing mechanism would be expected to produce changes in the circulatory system to preserve oxygen delivery and maintain brain oxygenation at the expense of systemic hypertensionThe mechanisms underlying sympathetic activation associated with compromised brain tissue perfusion and hypoxia remain unknown. This project was designed to test the hypothesis that brainstem hypoperfused is associated with the pathogenesis of systemic arterial hypertension (AU)

Scientific publications

(14)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ZOCCAL, DANIEL B.; SILVA, JOSIANE N.; BARNETT, WILLIAM H.; LEMES, EDUARDO V.; FALQUETTO, BARBARA; COLOMBARI, EDUARDO; MOLKOV, YAROSLAV I.; MOREIRA, THIAGO S.; TAKAKURA, ANA C.. Interaction between the retrotrapezoid nucleus and the parafacial respiratory group to regulate active expiration and sympathetic activity in rats. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, v. 315, n. 5, p. L891-L909, NOV 2018. (14/22406-1, 13/17251-6, 15/23376-1, 16/23281-3, 09/54888-7, 16/22069-0)

DIAZ, HUGO S.; ANDRADE, DAVID C.; TOLEDO, CAMILO; PEREYRA, V, KATHERIN; SCHWARZ, KARLA G.; DIAZ-JARA, ESTEBAN; LUCERO, CLAUDIA; ARCE-ALVAREZ, ALEXIS; SCHULTZ, HAROLD D.; SILVA, JOSIANE N.; et al. Episodic stimulation of central chemoreceptor neurons elicits disordered breathing and autonomic dysfunction in volume overload heart failure. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, v. 318, n. 1, p. L27-L40, JAN 2020. (16/22069-0, 15/23376-1, 16/23281-3)

MALHEIROS-LIMA, MILENE R.; TOTOLA, LEONARDO T.; LANA, MARLOUS V. G.; STRAUSS, BRYAN E.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.. Breathing responses produced by optogenetic stimulation of adrenergic C1 neurons are dependent on the connection with preBotzinger complex in rats. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 470, n. 11, p. 1659-1672, NOV 2018. (14/07698-6, 15/23376-1, 16/23281-3, 16/22069-0)

SOBRINHO, CLEYTON R.; GONCALVES, CHRISTOPHER M.; TAKAKURA, ANA C.; MULKEY, DANIEL K.; MOREIRA, THIAGO S.. Fluorocitrate-mediated depolarization of astrocytes in the retrotrapezoid nucleus stimulates breathing. Journal of Neurophysiology, v. 118, n. 3, p. 1690-1697, SEP 2017. (14/22406-1, 11/13462-7, 15/23376-1, 15/12827-2, 16/22069-0)

HAWKINS, VIRGINIA E.; TAKAKURA, ANA C.; TRINH, ASHLEY; MALHEIROS-LIMA, MILENE R.; CLEARY, COLIN M.; WENKER, IAN C.; DUBREUIL, TODD; RODRIGUEZ, ELLIOT M.; NELSON, MARK T.; MOREIRA, THIAGO S.; et al. Purinergic regulation of vascular tone in the retrotrapezoid nucleus is specialized to support the drive to breathe. eLIFE, v. 6, APR 7 2017. (14/07698-6, 14/22406-1, 15/23376-1, 16/22069-0)

MOREIRA, THIAGO S.; ANTUNES, VAGNER R.; FALQUETTO, BARBARA; MARINA, NEPHTALI. Long-term stimulation of cardiac vagal preganglionic neurons reduces blood pressure in the spontaneously hypertensive rat. Journal of Hypertension, v. 36, n. 12, p. 2444-2452, DEC 2018. (15/23376-1, 16/21991-3, 16/22069-0)

MOREIRA, THIAGO; MOREIRA, T. S.; TAKAKURA, A. C.; MULKEY, D. K.. Purinergic regulation of vascular tone in the retrotrapezoid nucleus is specialized to support the drive to breathe. PURINERGIC SIGNALLING, v. 14, p. 1-pg., 2018-12-01. (16/22069-0)

CZEISLER, CATHERINE M.; SILVA, TALITA M.; FAIR, SUMMER R.; LIU, JILLIAN; TUPAL, SRINIVASAN; KAYA, BEHIYE; COWGILL, AARON; MAHAJAN, SALIL; SILVA, PHELIPE E.; WANG, YANGYANG; et al. The role of PHOX2B-derived astrocytes in chemosensory control of breathing and sleep homeostasis. JOURNAL OF PHYSIOLOGY-LONDON, v. 597, n. 8, p. 2225-2251, APR 15 2019. (15/23376-1, 16/23281-3, 16/22069-0)

LIMA, JANAYNA D.; SOBRINHO, CLEYTON R.; FALQUETTO, BARBARA; SANTOS, LEONARDO K.; TAKAKURA, ANA C.; MULKEY, DANIEL K.; MOREIRA, THIAGO S.. Cholinergic neurons in the pedunculopontine tegmental nucleus modulate breathing in rats by direct projections to the retrotrapezoid nucleus. JOURNAL OF PHYSIOLOGY-LONDON, v. 597, n. 7, p. 1919-1934, APR 2019. (15/23376-1, 16/23281-3, 15/12827-2, 16/22069-0, 17/01380-2)

OLIVEIRA, LUIZ M.; FALQUETTO, BARBARA; MOREIRA, THIAGO S.; TAKAKURA, ANA C.. Orexinergic neurons are involved in the chemosensory control of breathing during the dark phase in a Parkinson's disease model. Experimental Neurology, v. 309, p. 107-118, NOV 2018. (16/23281-3, 16/22069-0, 17/12266-6, 15/23376-1, 15/18842-3, 15/11268-0)

MALHEIROS-LIMA, MILENE R.; ANTUNES, VAGNER R.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.. Hypertension and sympathetic nervous system overactivity rely on the vascular tone of pial vessels of the rostral ventrolateral medulla in spontaneously hypertensive rats. Experimental Physiology, v. 105, n. 1, p. 65-74, JAN 2020. (15/23376-1, 16/23281-3, 16/21991-3, 16/22069-0, 17/08696-5)

FALQUETTO, BARBARA; OLIVEIRA, LUIZ M.; TAKAKURA, ANA C.; MULKEY, DANIEL K.; MOREIRA, THIAGO S.. Inhibition of the hypercapnic ventilatory response by adenosine in the retrotrapezoid nucleus in awake rats. Neuropharmacology, v. 138, p. 47-56, AUG 2018. (15/23376-1, 16/23281-3, 16/22069-0)

SILVA, TALITA M.; CHAAR, LAIALI J.; SILVA, REINALDO C.; TAKAKURA, ANA C.; CAMARA, NIELS O.; ANTUNES, VAGNER R.; MOREIRA, THIAGO S.. Minocycline alters expression of inflammatory markers in autonomic brain areas and ventilatory responses induced by acute hypoxia. Experimental Physiology, v. 103, n. 6, p. 884-895, JUN 1 2018. (15/23376-1, 16/23281-3, 16/22069-0, 16/21991-3, 13/00401-5)

JAMES, S. D.; HAWKINS, V. E.; FALQUETTO, B.; RUSKIN, D. N.; MASINO, S. A.; MOREIRA, T. S.; OLSEN, M. L.; MULKEY, D. K.. Adenosine Signaling through A1 Receptors Inhibits Chemosensitive Neurons in the Retrotrapezoid Nucleus. ENEURO, v. 5, n. 6, NOV-DEC 2018. (14/04866-5, 15/23376-1, 16/22069-0)