K. Conlon et C. Kidd, Neuronal nitric oxide facilitates vagal chronotropic and dromotropic actions on the heart, J AUTON NER, 75(2-3), 1999, pp. 136-146
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.