Chronic angiotensin-II treatment potentiates HR slowing in Sprague-Dawley rat during acute behavioral stress

Abstract

This study examined the effect of 2-week infusion of angiotensin-II (Ang-II; 175 ng/kg/min) via minipump in rats (n=7) upon the mean arterial blood pressure (mBP) and heart rate (HR) response to an acute stress as compared to rats infused with saline (n=7). The acute stress was produced by a classical aversive conditioning paradigm: a 15s tone (CS+) followed by a half second tail shock. Baseline mBP in Ang-II infused rats (167.7±21.3 mm Hg; mean±SD) significantly exceeded that of controls (127.6±13.5 mm Hg). Conversely, baseline HR in the Ang-II infused rats (348±33) was significantly lower than controls (384±19 bpm). The magnitude of the mBP increase during CS+ did not differ between groups, but the HR slowing during CS+ in the Ang-II infused rats (-13.2±8.9 bpm) was significantly greater than that seen in controls (-4.2±5.5 bpm). This augmented bradycardia may be inferentially attributed to an accentuated increase in cardiac parasympathetic activity during CS+ in the Ang-II infused rats. The mBP increased above baseline immediately post-shock delivery in controls, but fell in the Ang-II infused rats, perhaps because of a 'ceiling effect' in total vascular resistance. This classical conditioning model of 'acute stress' differs from most stress paradigms in rats in yielding a HR slowing concomitant with a pressor response, and this slowing is potentiated by Ang-II.

Figure 1

Group average change (Δ) vs. baseline in mean arterial blood pressure (mBP) and in heart rate (HR) during 30 sec. pulsed tone (CS+; dark bar on time scale) followed by half second tail shock (left panels) and during 30 sec. steady tone (CS−) never followed by shock (right panels) in rats infused with saline (S; thin lines) and those infused for 2 weeks with angiotensin-II (Ang-II; 175ng/kg/min; thick lines). Amplitude of changes in mBP during CS+ did not differ between groups (upper left panel), but HR slowed significantly more in the Ang-II vs. saline group (lower left). Mean BP dropped transiently post-shock in Ang-II infused rats while mBP was elevated in saline-infused group. The transient drop in pressure following the initial ‘on response’ for CS− (i.e., trough) was accentuated in the Ang-II infused rats.