Angiotensin II disproportionally attenuates dynamic vagal and sympathetic heart rate controls

Abstract

To better understand the pathophysiological role of angiotensin II (ANG II) in the dynamic autonomic regulation of heart rate (HR), we examined the effects of intravenous administration of ANG II (10 microg.kg(-1).h(-1)) on the transfer function from vagal or sympathetic nerve stimulation to HR in anesthetized rabbits with sinoaortic denervation and vagotomy. In the vagal stimulation group (n = 7), we stimulated the right vagal nerve for 10 min using binary white noise (0-10 Hz). The transfer function from vagal stimulation to HR approximated a first-order low-pass filter with pure delay. ANG II attenuated the dynamic gain from 7.6 +/- 0.9 to 5.8 +/- 0.9 beats.min(-1).Hz(-1) (means +/- SD; P < 0.01) without affecting the corner frequency or pure delay. In the sympathetic stimulation group (n = 7), we stimulated the right postganglionic cardiac sympathetic nerve for 20 min using binary white noise (0-5 Hz). The transfer function from sympathetic stimulation to HR approximated a second-order low-pass filter with pure delay. ANG II slightly attenuated the dynamic gain from 10.8 +/- 2.6 to 10.2 +/- 3.1 beats.min(-1).Hz(-1) (P = 0.049) without affecting the natural frequency, damping ratio, or pure delay. The disproportional suppression of the dynamic vagal and sympathetic regulation of HR would result in a relative sympathetic predominance in the presence of ANG II. The reduced high-frequency component of HR variability in patients with cardiovascular diseases, such as myocardial infarction and heart failure, may be explained in part by the peripheral effects of ANG II on the dynamic autonomic regulation of HR.

Dynamic characteristics of heart rate control by the autonomic nervous system in rats

“…Nevertheless, the sympathetic transfer function approximated a second‐order delay system (Fig. 2) and its parameters were similar to those estimated between postganglionic sympathetic stimulation and HR response in rabbits (natural frequency, 0.06–0.07 Hz; damping coefficient, 1.34–1.53; and lag time, 0.51–0.65 s; Kawada et al 2009). If we calculate the corner frequency (frequency at which gain decreased by 3 dB from steady‐state gain; 0.04 ± 0.01 Hz) instead of natural frequency, our results are comparable to the corner frequency (0.01–0.02 Hz) found by Berger et al .…”

“…As preliminary results suggested that the transfer function from sympathetic stimulation to HR response in rats approximated a second‐order low‐pass filter with pure delay, as in the case of rabbits (Kawada et al 1996, 2009), we determined the parameters of the sympathetic transfer function using the following equation: where K is dynamic gain (in beats per minute per herz), f N is the natural frequency (in herz), ζ is the damping ratio, L is lag time (in seconds), and f and j represent frequency and imaginary units, respectively. The dynamic gain ( K , in beats per minute per herz) represents the asymptotic value of transfer gain as the frequency approaches zero, and corresponds to the steady‐state response in the step response.…”

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

“…Conversely, Ang-II pressor responses were associated with a fall in vagal discharge (three fibers), little change (4 fibers) or an increase, but an increase smaller than occurred in response to PE (1 fiber). In a recent and elegant study in anesthetized rabbits with SAD and vagotomy, Kawada, et al (2009) stimulated the peripheral end of the right vagus with vs. without background iv Ang-II administration (10 ng/kg/min). They reported that the gain of the transfer function from vagal stimulation to HR slowing decreased significantly with concomitant Ang-II administration vs. control (i.e., no Ang-II).…”

High‐frequency dominant depression of peripheral vagal control of heart rate in rats with chronic heart failure

“…) and reduces the dynamic gain of the transfer function from VNS to HR (Kawada et al . ). Du et al .…”