Influence of stress on a syncope-like response to water immersion in rats.

Abstract

Cardiovascular changes during water immersion stress in humans and rats suggest it may be the ideal behavioral procedure to investigate vagal correlates of stress. The majority of <italic>in vivo</italic> behavioral stressors predominately generate an increase in sympathetic activity. Consequently, autonomic disturbances resulting in exaggerated cardiac vagal activity are poorly understood. The studies in this dissertation characterized the cardiac vagal effects of a two-hour water immersion (30 cm of 25&deg;C water) in rats. Additionally, the impact of pharmacological interventions affecting the hypothalamic-pituitary-adrenal (HPA) axis as well as prior social stress was evaluated on cardiac vagal activity. The first study identified ECG changes associated with water immersion and the interaction between the HPA axis and vagal activity. Fifty percent of vehicle-treated rats sank prior to the end of the two-hour immersion, and were rescued subsequently. Bradycardia occurred in all rats within 10 minutes of water immersion and the PR interval of the ECG wave (indicative of vagal activity) was elevated. Interestingly, rats that sank exhibited an exaggerated bradycardia and elongated PR interval compared with non-sinking rats. Methylatropine nitrate attenuated these effects, confirming the role of the vagus nerve in the cardiovascular changes. Antalarmin, a CRF-1 receptor antagonist, increased PR interval and produced robust bradycardia during water immersion, thereby facilitating sinking. Antalarmin-induced effects were also blocked by methylatropine. The second study evaluated individual differences in blood pressure (MAP) and heart rate variability (HRV; sympatho-vagal activity) during water immersion. Rats that sank had a tendency towards higher MAP in response to immersion; however 5-10 seconds before sinking, MAP decreased by 41(+/-7) mmHg below resting. HRV was also elevated in sinking vehicle-treated and antalarmin-treated rats, suggesting an augmented vagal response to immersion. These cardiovascular effects were also blocked by administration of methylatropine, thereby inhibiting sinking. The third study identified the contribution of prior social stress on elevated vagal activity during novel water immersion and its effects on isoproterenol-induced tachycardia and hypotension. Prior social defeat by a conspecific aggressive male facilitated the rise in vagal activity and the decrease in HR without compromising the chronotropic or depressor response to beta-adrenergic receptor stimulation. These studies have demonstrated clearly that cold water immersion produces vasovagal, syncope-like cardiovascular changes in some, but not all rats. Additionally, these studies indicate that prior stress as well as CRF-receptor dynamics may, in part, modulate these cardiovascular events.