Submitted on April 5, 2007
Accepted on July 19, 2007
Angiotensin II attenuates myocardial interstitial acetylcholine release
in response to vagal stimulation
Toru Kawada1*, Toji Yamazaki2, Tsuyoshi Akiyama2, Meihua Li3, Can Zheng4, Toshiaki Shishido1, Hidezo Mori2, and Masaru Sugimachi1
1 Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Osaka, Japan
2 Department of Cardiac Physiology, National Cardiovascular Center Research Institute, Osaka, Japan
3 Japan Association for the Advancement of Medical Equipment, Tokyo, Japan; Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Osaka, Japan
4 Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Osaka, Japan; Japan Association for the Advancement of Medical Equipment, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: torukawa{at}res.ncvc.go.jp.
Although angiotensin II (Ang II) exerts a variety of effects on the cardiovascular system, its effects on the peripheral parasympathetic neurotransmission have only been evaluated by changes in heart rate (an effect on the sinus node). To elucidate the effect of Ang II on the parasympathetic neurotransmission in the left ventricle, we measured myocardial interstitial acetylcholine (ACh) release in response to vagal stimulation (1 ms, 10 V, 20 Hz) using cardiac microdialysis in anesthetized cats. In a control group (n=6), vagal stimulation increased the ACh level from 0.85±0.03 to 10.7±1.0 nM (mean±SEM). Intravenous administration of Ang II at 10 µg·kg-1·h-1 suppressed the stimulation-induced ACh release to 7.5±0.6 nM (P<0.01). In a group with pretreatment of intravenous Ang II receptor subtype 1 (AT1 receptor) blocker losartan (10 mg/kg, n=6), Ang II was unable to inhibit the stimulation-induced ACh release (8.6±1.5 vs. 8.4±1.7 nM). In contrast, in a group with local administration of losartan (10 mM, n=6) through the dialysis probe, Ang II inhibited the stimulation-induced ACh release (8.0±0.8 vs. 5.8±1.0 nM, P<0.05). In conclusion, intravenous Ang II significantly inhibited the parasympathetic neurotransmission through AT1 receptors. The failure of local losartan administration to nullify the inhibitory effect of Ang II on the stimulation-induced ACh release indicates that the site of this inhibitory action is likely at parasympathetic ganglia rather than at postganglionic vagal nerve terminals.
