Abstract
Background: Although sympathetic overactivity and vagal withdrawal aggravate heart diseases, the mechanism of the vagal withdrawal is not fully understood. We hypothesized that angiotensin II (ANGII) would attenuate the acetylcholine (ACh) release in the ventricle. Methods: We implanted a dialysis fiber into the left ventricular free wall and measured the ACh concentration in the dialysate during bilateral vagal stimulation (1 ms, 10 Hz, 10V) in anesthetized cats. Effects of intravenous ANGII at 10 μg/kg/h were examined (n=6). To examine the role of ANGII type 1 (AT1) receptors, an AT1 antagonist losartan was administered intravenously (10 mg/kg bolus, n=5) or locally through the dialysis probe (10 mM, n=6). Results: Vagal stimulation increased ACh from 0.85±0.08 to 10.7±2.4 nM (mean±SD). ANGII suppressed the ACh release to 7.5±1.4 (P<0.01). Local administration of losartan did not abolish the suppressive effect of ANGII on the stimulation-induced ACh release (from 8.0±2.0 to 5.8±2.4 nM, P<0.01) whereas the intravenous administration did (from 7.5±3.0 to 7.4±3.6 nM). Conclusion: ANGII suppressed the vagal stimulation-induced ACh release in the left ventricle. AT1 receptors at the postganglionic vagal nerve terminals were not involved in the site of this action. ANGII might act on the parasympathetic ganglia, thereby reducing the postganglionic vagal nerve activity and also contributing to the aggravation of heart diseases. [J Physiol Sci. 2007;57 Suppl:S81]
