Sodium nitroprusside increases pacemaker rhythm of sinoatrial nodes via nitric oxide-cGMP pathway

Effects of sodium nitroprusside (SNP), a nitric oxide donor, on the action potential in isolated guinea-pig sinoatrial nodes and ventricular papillary muscles were investigated. In the driven ventricular papillary muscle, SNP (10 ^-10 -10 ^-3 M) decreased the twitch tension in a concentration-dependent manner without significantly changing the configuration of action potential and the maximal velocity of depolarizing upstroke. In isolated sinoatrial nodes, SNP (10 ^-8 -10 ^-3 M) increased the pacemaker rhythm in a concentration-dependent manner. At 10 ^-5 M SNP, the pacemaker activity increased from 197.2± 6.1 to 221.4±9.7 bpm. Changes of configuration of the action potential included a decrease of the duration of repolarization, i.e., from peak to the maximal diastolic potential (MDP), from 141.4±6.4 to 130.0±7.0 nis and an increase of the slope of the diastolic membrane potential from 101.6±5.3 to 116.5± 7.3 mV/s (n=6, p<0.05). However, MDP and threshold potential were not significantly changed. Methylene blue (MB, 10 ^-5 M), a guanylate cyclase inhibitor, significantly decreased the pacemaker activity of the sinoatrial node by increasing the durations of repolarization and diastolic depolarization. After pretreatment with 10 ^-5 M MB, the effect of SNP was inhibited. The results indicate that nitric oxide, released from SNP, increases the pacemaker activity by enhancing the rates of repolarization and diastolic depolarization. These effects are possibly due to increases in delayed-rectifier K ⁺ and diastolic slow inward currents, which are involved in a mechanism associated with the NO-cGMP pathway.