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

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

MATERIALS AND METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.