Submitted on September 29, 2008
Revised on February 6, 2009
Accepted on February 25, 2009
Angiotensin II disproportionally attenuates dynamic vagal and sympathetic heart rate controls
Toru Kawada1*, Masaki Mizuno2, Shuji Shimizu, Kazunori Uemura1, Atsunori Kamiya1, and Masaru Sugimachi3
1 National Cardiovascular Center Research Institute
2 National Cardiovascular Centre Research Institute
3 National Cardiovascular Center
* To whom correspondence should be addressed. E-mail: torukawa{at}res.ncvc.go.jp.
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 µg•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 (mean ± 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.
