Abstract
KEY POINTS: We investigated the cardiovascular and respiratory responses of the normotensive Wistar-Kyoto (WKY) rat and the spontaneously hypertensive (SH) rat to inhalation and intravenous injection of the noxious stimuli allyl isothiocyanate (AITC). AITC inhalation evoked atropine-sensitive bradycardia in conscious WKY rats, and evoked atropine-sensitive bradycardia and atenolol-sensitive tachycardia with premature ventricular contractions (PVCs) in conscious SH rats. Intravenous injection of AITC evoked bradycardia but no tachycardia/PVCs in conscious SHs, while inhalation and injection of AITC caused similar bradypnoea in conscious SH and WKY rats. Anaesthesia (inhaled isoflurane) inhibited the cardiac reflexes evoked by inhaled AITC but not injected AITC. Data indicate the presence of a de novo nociceptive pulmonary-cardiac reflex triggering sympathoexcitation in SH rats, and this reflex is dependent on vagal afferents but is not due to steady state blood pressure or due to remodelling of vagal efferent function.
ABSTRACT: Inhalation of noxious irritants/pollutants activates airway nociceptive afferents resulting in reflex bradycardia in healthy animals. Nevertheless, noxious pollutants evoke sympathoexcitation (tachycardia, hypertension) in cardiovascular disease patients. We hypothesize that cardiovascular disease alters nociceptive pulmonary-cardiac reflexes. Here, we studied reflex responses to irritants in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive (SH) rats. Inhaled allyl isothiocyanate (AITC) evoked atropine-sensitive bradycardia with atrial-ventricular (AV) block in conscious WKY rats, thus indicating a parasympathetic reflex. Conversely, inhaled AITC in conscious SH rats evoked complex brady-tachycardia with both AV block and premature ventricular contractions (PVCs). Atropine abolished the bradycardia and AV block, but the atropine-insensitive tachycardia and PVCs were abolished by the β1 -adrenoceptor antagonist atenolol. The aberrant AITC-evoked reflex in SH rats was not reduced by acute blood pressure reduction by captopril. Surprisingly, intravenous AITC only evoked bradycardia in conscious SH and WKY rats. Furthermore, anaesthesia reduced the cardiac reflexes evoked by inhaled but not injected AITC. Nevertheless, anaesthesia had little effect on AITC-evoked respiratory reflexes. Such data suggest distinct differences in nociceptive reflex pathways dependent on cardiovascular disease, administration route and downstream effector. AITC-evoked tachycardia in decerebrate SH rats was abolished by vagotomy. Finally, there was no difference in the cardiac responses of WKY and SH rats to vagal efferent electrical stimulation. Our data suggest that AITC inhalation in SH rats evokes de novo adrenergic reflexes following vagal afferent activation. This aberrant reflex is independent of steady state hypertension and is not evoked by intravenous AITC. We conclude that pre-existing hypertension aberrantly shifts nociceptive pulmonary-cardiac reflexes towards sympathoexcitation.