Angiotensin II attenuates myocardial interstitial acetylcholine release in response to vagal stimulation

Abstract

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 ϭ 6), vagal stimulation increased the ACh level from 0.85 Ϯ 0.03 to 10.7 Ϯ 1.0 (SE) nM. Intravenous administration of ANG II at 10 g ⅐ kg Ϫ1 ⅐ h Ϫ1 suppressed the stimulation-induced ACh release to 7.5 Ϯ 0.6 nM (P Ͻ 0.01). In a group with pretreatment of intravenous ANG II receptor subtype 1 (AT1 receptor) blocker losartan (10 mg/kg, n ϭ 6), ANG II was unable to inhibit the stimulation-induced ACh release (8.6 Ϯ 1.5 vs. 8.4 Ϯ 1.7 nM). In contrast, in a group with local administration of losartan (10 mM, n ϭ 6) through the dialysis probe, ANG II inhibited the stimulation-induced ACh release (8.0 Ϯ 0.8 vs. 5.8 Ϯ 1.0 nM, P Ͻ 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. cardiac microdialysis; cats; losartan ANG II HAS a variety of effects on the cardiovascular system (22): it acts on the vascular beds to increase peripheral vascular resistance and also on the adrenal cortex to cause volume retention. These direct effects of ANG II contribute to the maintenance of arterial pressure (AP). Aside from these direct effects, ANG II has been shown to modulate the sympathetic nervous system both centrally (7, 9) and peripherally (10). With respect to the sympathetic regulation in the heart, however, exogenous ANG II does not facilitate stimulation-and ischemia-induced norepinephrine release in the porcine left ventricle (18). Compared with a number of reports on the sympathetic system, only a few reports are available as to the effects of ANG II on the parasympathetic system. In 1982, Potter (23) demonstrated that ANG II (5-10 g iv, body wt not reported) inhibited bradycardia induced by vagal stimulation in dogs. In that study, administration of ACh reduced the heart rate to an identical degree in the presence or absence of ANG II, suggesting that the inhibition of bradycardia by ANG II was attributable to the inhibition of the ACh release from the vagal nerve terminals. In contrast, Andrews et al. (3) reported that ANG II (500 ng/kg iv) did not inhibit bradycardia induced by vagal stimulation in ferrets. In a rat heart failure model, ANG II receptor subtype 1 (AT 1 receptor) antagonist losartan enhanced the bradycardic response to vagal stimulation (5). In pithed rats, an angiotensin-converting enzyme (ACE) inhibitor...

A Potential Role of Alpha-7 Nicotinic Acetylcholine Receptor in Cardiac Angiogenesis in a Pressure-Overload Rat Model

“…Although it is generally accepted that the vagus nerve innervates only the sino-atrial node and atrioventricular node in the heart, Kakinuma et al demonstrated that acetylcholine released from vagal stimulation had a protective effect on ischemic myocardium in rats (32), suggesting that acetylcholine may diffuse throughout the left ventricle. Studies also showed that vagal stimulation increased the acetylcholine levels in the left ventricle in rats (33) and acetylcholinesterase-positive nerves were found to be distributed in the ventricle of human hearts (34), indicating that acetylcholine from the vagus nerve was able to act on myocardial cells in the left ventricle. Thus it seems possible that vagus nerve function may influence expression of α7nAChR of myocardial cells in the left ventricle through acetylcholine.…”

Evidence for impaired vagus nerve activity in heart failure

“…Specifically, it has been demonstrated that administration of angiotensin II by intravenous route inhibited the bradycardia induced by vagal stimulation [54,55]. Kawada et al [56] demonstrated that angiotensin II may mediate these effects by decreasing the release of acetylcholine in response to vagal stimulation.…”

Acetylcholine prevents angiotensin II-induced oxidative stress and apoptosis in H9c2 cells

“…Kawada T et al [19] reported that intravenous injection of Ang II reduced vagal nerve stimulation-induced ACh release in the left ventricle, an effect that can be abolished by the Ang II antagonist losartan. These results imply that the beneficial effects of ACE inhibitors and AT1 receptor antagonists for CVD may include not only sympathetic activity suppression, but also an enhanced vagal activity in the ventricle.…”