Involvement of hypothalamic nitric oxide signaling in the modulation of a rat's exercise capacity

The aim of this study was to explore the effect of nitric oxide (NO) in some regions of the hypothalamus on exercise capacity.

To assess the role of central NO in exercise capacity, L-arginine (L-Arg, a precursor of NO synthesis), NG-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor), or placebo saline was injected into the lateral cerebral ventricle of rats once a day for 4 consecutive days. Thereafter, an one-time exhaustive treadmill exercise was performed, and the levels of nitrate/nitrite, as a marker of NO production, in blood plasma and hypothalamus were assayed. Neuronal nitric oxide synthase (nNOS)-expressing cells were immunohistochemically stained and analyzed in the paraventricular nucleus (PVN), the dorsomedial hypothalamus (DMH), and the ventromedial hypothalamus. Exercise time to exhaustion and total workload were determined.

Compared with the rats in the saline group, the exercise time to exhaustion and total workload increased 50% in the L-Arg group and decreased 50% in the L-NAME group. The nitrate/nitrite level of hypothalamus in the L-Arg group increased 50% and decreased 29.4% in the L-NAME group. The number of nNOS-positive cells was significantly increased, 56.5%, in PVN and, 119%, in DMH, but not in ventromedial hypothalamus. No significant changes in nNOS-positive cells were found in L-NAME-treated rats.

These results show that the modulation of hypothalamic NO signaling can affect the rat's running performance during a treadmill exercise and that enhanced NO signaling by induction of nNOS in PVN and DMH plays a role in improving exercise capacity after central administration of L-Arg. NO signaling in PVN and DMH may be a useful target for the pharmacological intervention of exercise performance or capacity.