The role of neuronal nitric oxide in the vagal control of cardiac interval of the rat heart in vitro

The aim of this study was to examine the role of neuronal nitric oxide (NO) on vagal regulation of the rat heart in vitro using the neuronal nitric oxide synthase (nNOS) inhibitor 1-(2-trifluoromethylphenyl) imidazole (TRIM). All experiments were carried out in the presence of the β-adrenoreceptor antagonist atenolol (4 μM). Right thoracic vagus, or its cardiac branch, was stimulated at frequencies of 2, 4, 8, 16 and 32 Hz (pulse duration 1 ms, 20 V, for 20 s) before and after addition of TRIM (0.14 mM) and cardiac interval (ms) assessed. There was a significant positive linear correlation between cardiac interval and vagal frequency giving a slope of 2.76±0.8 ms/Hz (slope±S.E. slope; data pooled from eight rats) which was significantly attenuated following TRIM to 0.4±0.6 ms/Hz (P<0.05 ANOVA; n=8 rats). Nicotine applied in cumulative concentrations (0.03, 0.1, 0.3, 0.5, 1 mM) caused a linear concentration-dependent increase in cardiac interval, with a slope of 403±72 ms/mM (n=10 rats) which was significantly attenuated after treatment with hexamethonium (28 μM), to 190±36 ms/mM (n=10 rats, P<0.05 ANOVA), and atropine (3 μM) 100±31 ms/mM (n=9 rats, P<0.05 ANOVA) but not following TRIM (0.14 mM) 262±48 ms/mM (n=9 rats, P<0.05 ANOVA). These results suggest that NO facilitates vagal effects on the rat heart in vitro by an action at the pre-ganglionic/post-ganglionic synapse.