Angiotensin ii modifies cardiomyocyte function via extracardiac and intracardiac neurons: in situ and in vitro studies. Horackova, Magda, and J. Andrew Armour. Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
APStracts 3:0335R, 1996.
To determine whether angiotensin II affects cardiac performance via neurons in intrathoracic cardiac ganglia studies were performed on anesthetized dogs. To exclude possible vascular regulatory effects of angiotensin II, experiments were also performed using long-term cultures of adult guinea-pig ventricular cardiomyocytes with or without intrathoracic neurons. (1) In situ experiments: In 10 anesthetized dogs, cardiac augmentation occurred when Ang II (10 [mu]l or 0.1 ml; 10-100 [mu]M) was administered into limited loci within acutely decentralized stellate or middle cervical ganglia which were neurally connected to, but not those disconnected from the heart. In other 18 dogs Ang II increased intrinsic cardiac neuronal activity when administered adjacent to such neurons or into their local arterial blood supply. Ventricular ionotropic effects elicited by Ang II were eliminated by timolol while increases in intrinsic cardiac neuronal activity were not affected. Effects elicited by Ang II were eliminated by administration of a selective AT1 receptor antagonist (losartan) but not by a selective AT2 receptor antagonist (PD-123319). (2) In vitro experiments: Ang II (100 nM) induced positive chronotropic effects on cultured adult guinea-pig cardiomyocytes innervated with adult extrinsic or intrinsic cardiac neurons, but not those cultured without neurons. The frequency of Cai transients (recorded by Fura-2 fluorescence) increased in innervated cocultures but not in the noninnervated cardiomyocyte cultures; however, the amplitude of Cai transients was not affected by Ang II in cultures or in freshly isolated adult guinea pig cardiomyocytes. Ang II-induced effects in cocultures were blocked by losartan but not PD-123319 or timolol. Thus (1) Ang II-sensitive neurons exist in intrathoracic extracardiac and intrinsic cardiac ganglia; (2) these neurons possess AT1 receptors; and (3) these neurons appear to act directly and indirectly via adrenergic neurons to enhance cardiomyocyte function. 

Received 20 May 1996; accepted in final form 13 August 1996.
APS Manuscript Number R279-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996