Neuronal nitric oxide facilitates vagal chronotropic and dromotropic actions on the heart

Previous studies, using non-specific nitric oxide synthase (NOS) inhibitors , have shown that nitric oxide (NO) has a significant facilitatory effect o n the actions of the vagus nerve on several aspects of cardiac function. Th e present study aims to identify a potential neuronal site for the action o f NO by using the n-NOS inhibitor, 1-(2-trifluoromethylphenyl) imidazole (T RIM) in the Ferret and other mammals. The effects of TRIM on vagally evoked alterations in heart rate and atrio-ventricular (a-v) conduction in the an aesthetised ferret, rabbit and guinea pig are described. In ferrets with bo th vagi sectioned and repeated infusions of propranolol, the vagally evoked , frequency-dependent bradycardia was significantly attenuated by infusion of TRIM (10-30 mg kg(-1)). This effect was reversed by subsequent infusion of L-arginine (20-6 mg kg(-1)). TRIM also attenuated to a similar extent th e vagally evoked bradycardia in similarly prepared guinea pigs, but NOS inh ibition and the use of the NO donor, molsidimine, failed to alter the heart rate effects of vagal stimulation in the rabbit. In studies on a-v conduct ion (dromotropy) in the ferret, electrical stimulation of the left cervical vagus increased the a-v conduction time in a frequency-dependent manner. A dministration of TRIM (30 mg kg(-1)) significantly attenuated this response . Again, L-arginine (60 mg kg(-1)) reversed it. Since an alteration in hear t rate may have a concomitant action on a-v conduction time, the effects of vagal stimulation on a-v conduction were also carried out in ferrets with the heart paced at a constant rate electrically. There was no significant d ifference between the effects of vagal stimulation obtained from hearts whi ch were paced and those which were unpaced. This implies that vagal stimula tion had a direct effect on a-v delay and the changes were not secondary to alterations in cardiac rate. Based on other evidence that TRIM is a powerf ul reversible n-NOS inhibitor in vivo, our studies support strongly the hyp othesis chat NO liberated from neuronal sources has an important facilitato ry action on the vagal control of the heart. In relation to vagal heart rat e control, it has now been shown that, in line with other studies in the do e and the rat, NO exerts a powerful facilitatory action in the ferret and t he guinea pig but not in the rabbit. It is to be expected that these effect s of NO will also be demonstrable on other vagal cardiac actions. (C) 1999 Elsevier Science B.V. All rights reserved.