The influence of carotidy chemoreflex to cutaneous blood flow during exercise in humans: implications for pulmonary hypertension

• Grant number: 21/14278-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): March 14, 2022
• Effective date (End): March 13, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Kátia de Angelis Lobo D Avila
• Grantee: Marcelle de Paula Ribeiro
• Supervisor: David Andrew Low
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Research place: Liverpool John Moores University (LJMU), England
• Associated to the scholarship: 19/27782-5 - Effect of exercise training on the contribution of carotid chemoreceptors to autonomic, cardiac and pulmonary vascular dysfunction in Pulmonary Arterial Hypertension:a translational perspective, BP.PD

Abstract

Pulmonary Arterial Hypertension (PAH) is a rare and progressive disease with poor prognosis. In PAH, vascular impairment is not restricted to pulmonary circulation as systemic vascular dysfunction has been reported. Accumulating evidence from my PhD study and others have shown that an augmented carotid chemoreflex contributes to the sympathetic hyperactivity at rest and overall cardiovascular dysfunction in patients with PAH, suggesting that this reflex might play an important role in the pathophysiology of this population. In addition, preliminary data from our Postdoctoral study is suggesting that the carotid chemoreflex contribution might be extended to the pulmonary vasculature in an experimental model of PAH. Based on the evidences indicating the influence of the carotid chemoreflex on cardiovascular modulation in PAH, it is possible that when stimulated, this reflex could also modulates the peripheral microcirculation. In this sense, the evaluation of cutaneous circulation during dynamic exercise carries particular relevance since the adjustments in cutaneous blood flow (CBF) during exercise is crucial to the maintenance of cardiac output and thermal homeostasis. Previous evidence have demonstrated that a sensitized carotid chemoreflex during exercise contributes to the skeletal muscle vasoconstriction, reducing the blood flow in both health and clinical conditions; however, the skeletal muscle blood flow may not be representative of the whole circulatory system; thus it remains to be determined if the contribution of carotid chemoreflex during exercise in humans extends to cutaneous territory. Given its potential clinical relevance, understanding how chemoreflexes influence the healthy human circulation is needed to further understand its functioning in all forms of PH. The aim of this project is to test 2 hypotheses: 1) inhibition of carotid chemoreceptors with brief hyperoxia inhalation will increase the cutaneous vasodilation response (increase in CBF) to exercise. 2) stimulation of the carotid chemoreceptors with a transient hypoxic PH model in healthy humans will attenuate the cutaneous vasodilation (reduction in CBF) response to exercise. Eight males and 8 females will perform a protocol of resting followed by dynamic exercise (cycle ergometer) under 3 situations (random order): inhibition of carotid chemoreflex through hyperoxia, stimulation of carotid chemoreflex through hypoxia or a control condition through normoxia. Gases inhalation will be maintained during 3 minutes. Functional assessment of CBF will be performed via laser Doppler Flowmetry. Data will be expressed as mean ± standard deviation. CBF and other variables will be compared between conditions using paired Student's t test or one-way repeated measure ANOVA (P < 0.05). (AU)