Altered Cardiopulmonary Reflexes Evoked by Irritants in Spontaneously Hypertensive Rats – Effect of Route of Administration and Anesthetics

Abstract

Inhalation of noxious substances such as allyl isothiocyanate (AITC) evoke reflex bradycardia in conscious, healthy animals following the activation of airway nociceptive afferents. These afferents are also activated by air pollutants including particulate matter and ozone. Nevertheless, in patients with cardiovascular disease such pollutants evoke sympathoexcitation (tachycardia, hypertension). We hypothesize that preexisting cardiovascular disease remodels the pulmonary‐cardiac reflexes stimulated by noxious airway stimuli. Here, we studied the cardiopulmonary responses to two separate administration methods of AITC (inhalation and intravenous (i.v.) injection) in conscious and anesthetized normotensive Wistar‐Kyoto rats (WKY) and Spontaneously Hypertensive rats (SH). Both methods of AITC administration evoked bradycardia with increased RR‐interval (RRi) and atrial‐ventricular (AV) block in conscious WKY rats. AITC i.v. evoked similar bradycardic responses in conscious SH rats, however, AITC inhalation evoked a complex brady‐tachycardia which alternated between increased and decreased RRi and both AV block and premature ventricular contractions (PVCs). AITC inhalation caused bradypnea with sporadic episodes of tachypnea in both strains, while only bradypnea was seen after AITC i.v. administration. These responses were shown to be vagally mediated as they were abolished by bilateral vagotomy in a decerebrate model. Anesthesia was also found to prevent the effect of AITC inhalation on HR in both strains, while the bradycardic response to AITC i.v. persisted in the WKY but not in the SH. Furthermore, anesthesia prevented breathing rate responses to inhaled AITC in the SH, but not in the WKY. Differences were also seen in the effects of anesthesia on breathing rate responses to AITC iv between the two strains as bradypnea persisted in the WKY, while the SH was found to have bouts of tachypnea in addition to the bradypnea seen in the conscious studies. The differential responses evoked by AITC in the SH along with the differences in effects of anesthesia on these responses lead us to conclude that multiple unique circuits work independently to control cardiopulmonary reflexes and that preexisting hypertension remodels nociceptive cardiopulmonary reflexes towards sympathoexcitation.Support or Funding InformationNIH SPARC AwardThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.