Effect of exercise training on the contribution of carotid chemoreceptors to autonomic, cardiac and pulmonary vascular dysfunction in Pulmonary Arterial Hypertension:a translational perspective

• Grant number: 19/27782-5
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): October 01, 2020
• Effective date (End): September 30, 2022
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal researcher: Kátia de Angelis Lobo D Avila
• Grantee: Marcelle de Paula Ribeiro
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Pulmonary Arterial Hypertension (PAH) is a rare and progressive disease, with multiple etiologies and poor prognosis. The cardiovascular autonomic dysfunction plays a role on PAH pathophysiology, contributing to clinical deterioration and disease progression. Recently, clinical studies have been shown that the exacerbation of carotid chemoreflex activity might be one potential mechanism involved on autonomic dysfunction in PAH. However, Exercise training (EXT) has been shown to abrogate/attenuate carotid chemoreflex hyperactivity in different cardiorespiratory diseases. The aforementioned evidences justify further investigation regarding the extent of carotid chemoreflex activity to pathophysiology of PAH, as well as the potential effect of EXT on carotid chemoreflex-mediated autonomic dysfunction in PAH. The hypotheses of the study are: 1) carotid chemoreflex hyperactivity contributes to autonomic, cardiac and pulmonary vascular dysfunction in PAH; 2) Combined EXT (aerobic followed by resistance training) is effective in partially normalize the carotid chemoreflex-mediated cardiovascular dysfunction in PAH. To test these hypotheses, a translational protocol will be developing at the Federal University of Sao Paulo (UNIFESP) in collaboration with the University of Sao Paulo (USP). In sedentary and trained rats (combined EXT, moderate intensity, 5 days/week; 5 weeks) with PAH induced by monocrotaline (n = 72), tonic carotid chemoreflex activity will be evaluated by bilateral carotid body ablation. In sedentary and trained (combined EXT, moderate intensity, 2 days/week; 12 weeks) patients with PAH (n = 30), tonic carotid chemoreflex activity will be evaluated following hyperoxic inhalation. The confirmation of the aforementioned hypotheses could demonstrate the carotid chemoreflex as a potential mechanism involved on the pathophysiology of PAH, and more importantly, the combined EXT as a non-pharmacologic strategy to attenuate the carotid chemoreflex-mediated cardiovascular abnormalities in this population. (AU)