Intermittent hypoxia modulates nNOS expression and heart rate response to sympathetic nerve stimulation.

Nitric oxide (NO) decreases norepinephrine (NE) release and the heart rate (HR) response to sympathetic nerve stimulation (SNS). We tested the hypothesis that the enhanced HR response to sympathetic activation following chronic intermittent hypoxia (IH) results from a peripheral modulation of pacemaking by NO. Isolated guinea pig double atrial/right stellate ganglion preparations were studied from animals that had been exposed to IH (n = 20) and control animals (n = 22). The HR response to SNS was significantly enhanced in the IH group compared with the controls. However, the increase in HR with cumulative doses (0.1--10 microM) of bath-applied NE was similar in both groups. Western blot analysis showed less neuronal NO synthase in the right atria from the IH group. In IH animals, the NO synthase inhibitor, N(omega)-nitro-L-arginine (L-NNA; 100 microM) did not alter the increased HR response to SNS, whereas in control animals L-NNA significantly increased the HR response to SNS; an effect that was reversed with excess L-arginine. In conclusion, the enhanced HR response to SNS after IH may be related to a decreased inhibitory action of NO on presynaptic NE release.