Control of respiratory rhythm by purinergic mechanisms in spontaneously hypertensive animals

• Grant number: 24/22604-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2025
• End date: October 31, 2029
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Daniel Breseghello Zoccal
• Grantee: Beatriz Nunes Vieira
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 22/05717-0 - Analyzing breathing irregularities during the post-natal period in spontaneously hypertensive rats, AP.R

Abstract

Arterial hypertension (AH) is a relevant cardiovascular disease with high prevalence in the Brazilian and global population, and its etiology is not fully understood. Evidence indicates that the development of essential AH is associated with alterations in the central nervous system (CNS), leading to sympathetic hyperactivity and increased vascular resistance. One of the factors that can modify the functioning of the sympathetic nervous system is the reduced supply of oxygen to the CNS during the postnatal period. Exposure to hypoxia during the early days of postnatal life is a significant risk factor for the onset of sympathetic nervous system dysfunctions and hypertension in adulthood. Recent studies from our research group show that the elevated blood pressure levels in adult spontaneously hypertensive rats (SHR), an experimental model for essential AH, are correlated with the presence of spontaneous respiratory irregularities, hypoventilation, and hypoxemia during postnatal life. The respiratory dysfunctions in SHR animals are observed from birth, indicating innate modifications in the central mechanisms controlling respiration. In vitro studies from our group confirm this possibility and show that neonatal SHR rats exhibit alterations in the functioning of the respiratory generator located on the ventral surface of the medulla - the preBötzinger complex (preBötC). In the present project, we will study modifications in the modulatory mechanisms of the preBötC in SHR animals that may influence the control of respiratory rhythm and lead to post-natal hypoxemia. We will explore the hypothesis that respiratory alterations in neonatal SHR animals result from sensitization of the respiratory rhythm-generating neurons to purinergic signaling derived from preBötC astrocytes. To reach this goal, we will perform electrophysiological recordings, pharmacological manipulations, and Ca2+ imaging in in vitro preparations (rhythmic slices), allowing us to isolate and explore the rhythm-generating mechanisms of the preBötC and its connections with motor nuclei. Thus, studying the mechanisms related to the onset of respiratory irregularities in SHR animals may bring new perspectives on the etiology of essential AH. (AU)