Irritant Inhalation Evokes P Wave Morphological Changes in Spontaneously Hypertensive Rats via Reflex Modulation of the Autonomic Nervous System

Abstract

Irritant inhalation is associated with increased incidence of atrial fibrillation (AF) and stroke. Irritant inhalation acutely regulates cardiac function via autonomic reflexes. Increases in parasympathetic and sympathetic reflexes may increase atrial susceptibility to ectopic activity and the initiation of arrhythmia such as AF. Both age and hypertension are risk factors for AF. We have shown that irritant-evoked pulmonary–cardiac reflexes are remodeled in spontaneously hypertensive (SH) rats to include a sympathetic component in addition to the parasympathetic reflex observed in normotensive Wistar-Kyoto (WKY) rats. Here, we analyzed P wave morphology in 15-week old WKY and SH rats during inhalation of the transient receptor potential ankyrin 1 agonist allyl isothiocyanate (AITC). P Wave morphology was normal during vehicle inhalation but was variably modulated by AITC. AITC increased RR intervals (RRi), PR intervals, and the P Wave duration. In SH rats only, AITC inhalation increased the occurrence of negative P waves. The incidence of AITC-evoked negative P waves in SH rats was dependent on RRi, increasing during bradycardic and tachycardic cardiac cycles. Inhibition of both parasympathetic (using atropine) and sympathetic (using atenolol) components of the pulmonary–cardiac reflex decreased the incidence of negative P waves. Lastly, the probability of evoking a negative P Wave was increased by the occurrence of preceding negative P waves. We conclude that the remodeled irritant-evoked pulmonary–cardiac reflex in SH rats provides a substrate for altered P Wave morphologies. These are likely ectopic atrial beats that could provide a trigger for AF initiation in structurally remodeled atria.

Normal-Weight Abdominal Obesity: A Risk Factor for Hypertension and Cardiometabolic Dysregulation

“…Recent studies have pointed out that upregulation of the sympathetic nervous system is an important mechanism underlying obesity-related hypertension. [38,39,42,43] Also, leptin released by adipose tissue disturbs the hypothalamic neuronal systems, which can subsequently reduce food consumption, upregulate energy expenditure, and stimulate sympathetic activity.…”

“…Adipose tissue, once thought to be a simple energy warehouse, is now recognized to interact with systemic inflammatory responses, the sympathetic nervous system, and the renin-angiotensin system, facilitating obesity-related cardiometabolic dysregulation and contributing to the development of hypertension. Recent studies have pointed out that upregulation of the sympathetic nervous system is an important mechanism underlying obesity-related hypertension [38,39,42,43] . Also, leptin released by adipose tissue disturbs the hypothalamic neuronal systems, which can subsequently reduce food consumption, upregulate energy expenditure, and stimulate sympathetic activity.…”

Beneficial Health Effects of Glucosinolates-Derived Isothiocyanates on Cardiovascular and Neurodegenerative Diseases

“…The latter effect was explained as a brief hypertensive phase followed by a hypotensive phase occurring secondary to TRPA1 channel activation associated with stimulation of autonomic sensory neurons [ 213 ]. In SHRs alone, AITC caused abnormal electrocardiogram (ECG) pattern with increased occurrence of negative P and duration of P waves, and also increased PR and RR intervals than in controls [ 214 ].…”

“…However, caution is needed in clinical trials involving heart disease patients. Therefore, the inhalational route might not be a good gateway for AITC treatment for patients with background heart disease and hypertension [ 214 ].…”

A predictive model of response to metoprolol in children and adolescents with postural tachycardia syndrome

“…During sympathetic stimulation, the action potential of the atrial muscle cell is shortened; the slope of phase 0 increases; the refractory period is compressed; the automaticity is elevated; the triggering activity is enhanced, and the P wave voltage, P wave maximum time, and P wave dispersion can be significantly increased [ 12 , 33 ]. Hooper et al [ 34 ] observed a significant and positive increase in P wave duration when rats inhaled allyl isothiocyanate (AITC), an experimental agent exciting the sympathetic nerves. Cheema et al [ 12 ] observed that epinephrine infusion prolonged P wave duration in healthy volunteers.…”