Angiotensin II attenuates myocardial interstitial acetylcholine release in response to vagal stimulation.
Although 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 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 (SE) nM. Intravenous administration of ANG II at 10 microg x kg(-1) x 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 (AT(1) 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 AT(1) 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.
Kawada
Toru
T
Dept. of Cardiovascular Dynamics, Advance Medical Engineering Center, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. torukawa@res.ncvc.go.jp
Yamazaki
Toji
T
Akiyama
Tsuyoshi
T
Li
Meihua
M
Zheng
Can
C
Shishido
Toshiaki
T
Mori
Hidezo
H
Sugimachi
Masaru
M
D000109:Acetylcholine / Q000378:metabolism*; D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004558:Electric Stimulation; D005726:Ganglia, Parasympathetic / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D006352:Heart Ventricles / Q000294:innervation / Q000378:metabolism; D007262:Infusions, Intravenous; D019808:Losartan / Q000008:administration & dosage; D017551:Microdialysis; D009206:Myocardium / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D019808:Losartan; D000109:Acetylcholine