Chronic RAS Inhibition Prevents Aberrant Irritant-evoked Pulmonary-Cardiac Reflexes in the Spontaneously Hypertensive (SH) Rat

Abstract

Cardiopulmonary reflexes evoked by activation of airway vagal afferent nerves via irritant/pollution inhalation are remodeled from bradycardia in normal subjects to tachycardia and ventricular arrhythmia in patients with pre-existing cardiovascular disease (CVD). We have shown similar remodeling in the spontaneously hypertensive (SH) rat: selective activation of airway vagal afferent nerves via inhalation of the transient receptor potential ankyrin 1 (TRPA1)-specific agonist allyl isothiocyanate (AITC) evoked parasympathetic-mediated reflex bradycardia in normotensive wistar-kyoto rats but evoked sympathetically-mediated tachycardia and premature ventricular contractions (PVCs) in spontaneously hypertensive (SH) rats. Hypertension in the SH rat develops with age (~7 weeks) and this is accompanied by autonomic dysfunction.The renin-angiotensin system (RAS) is closely linked with blood pressure (BP), cardiac remodeling and autonomic dysfunction, with the main effector being angiotensin II (Ang II), produced downstream of angiotensin converting enzyme (ACE). Acute treatment with ACE inhibitors or antagonists of Ang II-sensitive receptor AT1R causes temporary BP normalization in SH rats. Chronic treatment with ACE inhibitors or AT1R inhibitors prevents the development of hypertension, baroreceptor dysfunction and cardiac remodeling in SH rats. Previously, we have shown that acute normalization of BP with the ACE inhibitor captopril had no effect on the AITC-evoked pulmonary-cardiac reflexes in the SH rat. Here, we investigated the impact of chronic ACE inhibitor treatment (captopril, 20mg/kg/ ad libitum) or chronic AT1R treatment (losartan, (15mg/kg/ ad libitum) from 6-15 weeks of age in SH rats on AITC-evoked pulmonary-cardiac reflexes. Both chronic captopril and losartan normalized BP and prevented AITC-evoked tachy-arrhythmia (% of tachycardic beats and PVCs) in SH rats at 15 weeks of age. As such, following antiRAS treatment, AITC only evoked reflex bradycardia in SH rats (similar to our previous studies of normotensive rats). These findings suggest that the remodeling of the irritant-evoked pulmonary-cardiac reflexes can be prevented by targeting the renin-angiotensin system. Reducing tachyarrhythmia evoked by the inhalation of irritants/pollution in susceptible individuals may reduce the risk of CVD exacerbations associated with air pollution. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.