title: Decreased contractility of the left ventricle is induced by the neurotransmitter acetylcholine, but not by vagal stimulation in rats.
abstract: There is still controversy with respect to how an increase in vagal tone changes left ventricular (LV) contractility. It is possible that a difference in LV vagal innervation density may affect the inotropic effect. To test this, we examined the effects of vagal stimulation and acetylcholine (ACh) infusion on the rat ventricle, in which LV vagal innervation density is sparse and a negative force-frequency relationship is uniquely observed. To evaluate LV contractility, we developed an in situ Langendorff preparation, in which the effects of changes in afterload, preload, and coronary flow during an intervention were minimized. Both vagal stimulation and ACh infusion significantly increased LV systolic pressure (34 +/- 16%: 36 +/- 22%. respectively) and its maximum positive first derivative with slowing of heart rate (51 +/- 17%: 46 +/- 18%). These effects of vagal stimulation were abolished by pretreatment with atropine. During a fixed heart rate, LV systolic pressure was not changed by vagal stimulation, however, it was decreased slightly but significantly (11 +/- 8%) by ACh infusion. In conclusion, LV contractility changes due to ACh release during vagal stimulation were negligibly small, presumably due to a sparse vagal innervation density in rats, and therefore, a bradycardia-dependent indirect positive inotropic effect may be dominant compared to a direct negative inotropic action during vagal stimulation. Thus, the integrated effect of vagal nerve stimulation on LV contractility is different among species, because it is determined by a direct negative inotropic effect, which depends on the vagal innervation density in the left ventricle, as well as by bradycardia-dependent indirect inotropic changes.
authors.affiliation: First Department of Internal Medicine, Fukushima Medical University, Fukushima city, Fukushima, Japan.
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Kazuhira
authors.initials: K
authors.lastname: Maehara
authors.forename: Norio
authors.initials: N
authors.lastname: Onuki
authors.forename: Tomiyoshi
authors.initials: T
authors.lastname: Saito
authors.forename: Yukio
authors.initials: Y
authors.lastname: Maruyama
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D003864:Depression, Chemical; D004558:Electric Stimulation; D006339:Heart Rate / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects*; D010275:Parasympathetic Nervous System / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014630:Vagus Nerve / Q000502:physiology*; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D001285:Atropine; D000109:Acetylcholine