L‐Menthol Inhibits Cardiac Sympathoexcitation Caused by Inhaled Irritants in the Spontaneously Hypertensive Rat

Abstract

Inhalation of irritants (e.g. particulate matter and ozone) triggers various efferent responses through activation of transient receptor potential ankyrin 1 (TRPA1) and TRP vanilloid 1 (TRPV1) channels expressed on airway vagal afferent nerves. In the airways they cause cough and mucus secretion and in conscious, healthy animals parasympathetic‐mediated reflexes include bradycardia and atrioventricular block. However, inhalation of air pollutants including particulate matter and ozone evokes sympathoexcitation (tachycardia, hypertension) in patients with cardiovascular disease. Interestingly, selective activation of airway vagal afferent nerves in spontaneously hypertensive (SH) rats via inhalation of the TRPA1‐specific agonist allyl isothiocyanate (AITC) evoked sympathetic‐mediated tachycardia and premature ventricular contractions (PVCs) consistent with reflexes evoked by inhaled pollution in patients with cardiovascular disease.Airway reflexes such as cough have been shown to be inhibited by nasal stimulation with L‐menthol via activation of cold‐sensitive trigeminal pathways which regulate brainstem respiratory networks. Here, we investigated the cardiac reflexes evoked by inhalation of L‐menthol (150mg/ml) alone and in combination with AITC (4.7mg/ml) in conscious SH rats. L‐menthol inhalation alone had no effect on heart rate, but, when inhaled during AITC inhalation, L‐menthol selectively inhibited the AITC‐evoked tachyarrhythmia. Inhibition of the AITC‐evoked sympathoexcitatory reflexes was not seen in identical studies performed with inactive D‐menthol (150mg/ml). Therefore, we conclude that pulmonary‐cardiac reflex tachyarrhythmia are reduced by activation of nasal menthol‐sensitive pathways. This data supports the potential for prevention of aberrant irritant‐evoked pulmonary‐cardiac reflexes by nasal menthol treatment.Support or Funding InformationNIH r56