A reversal of fate : unravelling the role of central 5-HT in cardiorespiratory control in neonatal and adult rodents

Abstract

We seek to address the extent to which a specific loss of 5-hydroxytryptamine (5-HT) affects the control of respiration, arterial blood pressure (ABP) and heart rate (HR) across vigilance-states based on existing evidence suggesting that 5-HT defects increase the risk for Sudden Infant Death Syndrome (SIDS) and neurogenic hypertension. SIDS is the leading cause of infant mortality between 1 month and 1 year of age, occurs during sleep, and up to 70% of all SIDS cases have at least one 5-HT system abnormality. Neonatal rodents lacking central 5-HT exhibit severe apneas, and a reduced ABP and HR. Central 5-HT has been implicated in the etiology of neurogenic hypertension, presumably due to projections of 5-HT neurons within the midline raphe to vagal and presympathetic regions of the brain. However, data from studies examining the specific role of central 5-HT function is conflicting or inconclusive. Neurogenic hypertension accounts for more than 90% of all hypertensive cases and the normal fall in ABP that occurs during non-rapid eye movement sleep is absent in some patients with hypertension. Understanding the mechanisms associated with the development of hypertension is critical not only to lower blood pressure, but to lower its associated cardiovascular events. The purpose of this dissertation is to examine the role of central 5-HT in the control of ABP during sleep and reveal, mechanistically, the physiological role of 5-HT in the autonomic control of ABP in neonatal and adult rodents. The overarching hypothesis for this dissertation is that central 5-HT is required for the maintenance of ABP and autonomic tone at rest in both neonatal and adult rodents.