title: 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.
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: J S
authors.initials: JS
authors.lastname: Hooper
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: S H
authors.initials: SH
authors.lastname: Hadley
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: K F
authors.initials: KF
authors.lastname: Morris
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: J W
authors.initials: JW
authors.lastname: Breslin
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: J B
authors.initials: JB
authors.lastname: Dean
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida ttaylorc@health.usf.edu.
authors.forename: T E
authors.initials: TE
authors.lastname: Taylor-Clark
mesh_terms: D000255:Adenosine Triphosphate / Q000009:adverse effects / Q000494:pharmacology*; D000393:Air Pollutants / Q000009:adverse effects; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000378:metabolism; D001919:Bradycardia / Q000139:chemically induced / Q000378:metabolism; D002211:Capsaicin / Q000009:adverse effects / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism; D017879:Isothiocyanates / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D012137:Respiratory System / Q000187:drug effects* / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects; D050052:TRPC Cation Channels / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D017879:Isothiocyanates; D050052:TRPC Cation Channels; D000255:Adenosine Triphosphate; C004471:allyl isothiocyanate; D002211:Capsaicin
keywords: TRPA1; airways; autonomic nervous system; cardiovascular response; nociceptive sensory nerves