Characterization of cardiovascular reflexes evoked by airway stimulation with allylisothiocyanate, capsaicin, and ATP in Sprague-Dawley rats

Abstract

Acute inhalation of airborne pollutants alters cardiovascular function and evidence suggests that pollutant-induced activation of airway sensory nerves via the gating of ion channels is critical to these systemic responses. Here, we have investigated the effect of capsaicin [transient receptor potential (TRP) vanilloid 1 (TRPV1) agonist], AITC [TRP ankyrin 1 (TRPA1) agonist], and ATP (P2X2/3 agonist) on bronchopulmonary sensory activity and cardiovascular responses of conscious Sprague-Dawley (SD) rats. Single fiber recordings show that allyl isothiocyanate (AITC) and capsaicin selectively activate C fibers, whereas subpopulations of both A and C fibers are activated by stimulation of P2X2/3 receptors. Inhalation of the agonists by conscious rats caused significant bradycardia, atrioventricular (AV) block, and prolonged PR intervals, although ATP-induced responses were lesser than those evoked by AITC or capsaicin. Responses to AITC were inhibited by the TRP channel blocker ruthenium red and the muscarinic antagonist atropine. AITC inhalation also caused a biphasic blood pressure response: a brief hypertensive phase followed by a hypotensive phase. Atropine accentuated the hypertensive phase, while preventing the hypotension. AITC-evoked bradycardia was not abolished by terazosin, the α1-adrenoceptor inhibitor, which prevented the hypertensive response. Anesthetics had profound effects on AITC-evoked bradycardia and AV block, which was abolished by urethane, ketamine, and isoflurane. Nevertheless, AITC inhalation caused bradycardia and AV block in paralyzed and ventilated rats following precollicular decerebration. In conclusion, we provide evidence that activation of ion channels expressed on nociceptive airway sensory nerves causes significant cardiovascular effects in conscious SD rats via reflex modulation of the autonomic nervous system.

Sympatho-excitatory response to pulmonary chemosensitive spinal afferent activation in anesthetized, vagotomized rats

“…; Hooper et al. ), and the distribution of spinal afferent neurons within the lung is unknown. Early studies indicated that tracheal afferent nerve fibers originated in the C1 and T1–T4 DRG (Dalsgaard and Lundberg ; Kummer et al.…”

“…However, the exact role and function of spinal afferent neurons in the lung is still unknown. Previous studies have indicated pressor, depressor, and biphasic blood pressure responses to cardiopulmonary spinal afferent activation (Weaver 1977;Kostreva et al 1981;Wang et al 2003;Soukhova-O'Hare et al 2006;Hooper et al 2016). The differences in whether an excitatory or inhibitory blood pressure response was observed in these studies are likely due to the preparations and experimental protocols used.…”

“…; Hooper et al. ). The differences in whether an excitatory or inhibitory blood pressure response was observed in these studies are likely due to the preparations and experimental protocols used.…”

“…Stimulation of vagal sensory fibers has been shown to regulate rate and depth of breathing, basal tidal volume via the Herring-Breuer reflex (Carr and Undem 2003) (Paintal 1973) (Widdicombe and Lee 2001), cough (Canning and Chou 2009;Taylor-Clark 2015), and innervation of neuroepithelial bodies (Chang et al 2015). The bradycardia observed in response to lung inflation (Shepherd 1981) and to inhalation of noxious stimuli (Hazari et al 2011;Hooper et al 2016) is thought to be mediated by afferents of vagal origin.…”

Purinergic Signaling in the Cardiovascular System

“…148,149 Activation of P2X2/3 receptors expressed on nociceptive airway sensory nerves causes cardiovascular reflexes in conscious rats via reflex modulation of the autonomic nervous system. 150 The responses to adenosine of the transplanted human heart show supersensitivity. Donor pretreatment with AMP-activated PK activator protects cardiac grafts from cold ischemia/reperfusion injury.…”