The role of nitric oxide in the neural control of the heart
The role of nitric oxide in the neural control of heart function was investigated in vivo in a variety of animal species. Inhibition of nitric oxide synthase using specific and non specific inhibitors significantly attenuated chronotropic, dromotropic and inotropic responses to vagal stimulation in the anaesthetised ferret, rat and guinea pig. The nNOS inhibitor TRIM had no effect on vagally induced bradycardia in the anaesthetised rabbit. Nitric oxide donors enhanced vagally induced actions on heart rate in the ferret and the rat. Donors also enhanced the dromotropic actions of the vagus in the ferret. The NO donor molsidomine had no effect on heart rate responses to vagal stimulation in the rabbit. In the ferret, NOS inhibitors enhanced the heart rate response to sympathetic nerve stimulation. The nitric oxide donor sodium nitroprusside attenuated this response in a dose dependent manner. The NOS inhibitor L-NAME attenuated the inotropic response to vagal stimulation in the ferret. These effects were reversed with L-arginine. A study of the interaction between vagal and sympathetic influences on heart rate in the ferret demonstrated the principle of accentuated antagonism under control conditions. A study on the interaction after NOS inhibition revealed a dominant role for NO in vagal actions on heart rate when the two divisions of the autonomic nervous system are active. The results strongly suggest a role for nitric oxide in the neural control of heart function in a variety of animal species. Species differences do occur. In addition, the results have implications for the modulation of vagal tone, both during normal physiology and during patterns of abnormal cardiac autonomic drive.