Role of Nitric Oxide in the Autonomic Modulation of Atrioventricular Nodal Conduction in Dogs

Introduction. Nitric oxide (NO), synthesized from L-arginine, is involved in the modulation of autonomic neurotransmission. Recent in vitro and in vivo studies have shown that the negative chronotropic effect of carbachol or vagal stimulation was partially blocked by an L-arginine analog, NG-monomethyl-L-arginine (L-NMMA), that competetively inhibits NO synthase (NOS). The purpose of the present study was to assess in an open chest canine model whether the L-arginine-NO pathway may also play role in the autonomic modulation of AV nodal conduction, and if so, whether this is prejunctional or postjunctional. Methods and Results. To test for prejunctional actions, we assessed the dromotropic response to cervical vagal stimulation (VS: 2 Hz, 4.0 V, 4 ms) and VS during ansae subclaviae stimulation (SS: 2 Hz, 3.0 V, 4 ms, N = 5). To test for postjunctional actions, we determined the dromotropic response to intravenous isoproterenol infusion (5 mcg/min) before and during vagal stimulation (VS + ISO, N = 5). VS, SS and ISO were repeated during selective infusion of L-NMM retrogradely into the AV node artery (AVNA) and following reversal of NOS inhibition with L-arginine (100 mg/kg). Shown is the change in AV nodal conduction time (AH, msec) produced by VS before and during SS or isoproterenol at control state (saline infusion into AVNA, 1 ml/min), during L-NMM infusion (4 mg/min) into AVNA, and after IV injection of L-arginine (100 mg/kg). Conclusion. The negative dromotropic effect of VS, VS during SS and ISO is attenuated by L-NMM and restored toward baseline by L-arginine, suggesting that NO plays partial role at both prejunctional and postjunctional sites in the vagal modulation of AV nodal conduction.