Neurochemical mechanisms of nitroglycerin-induced neuronal activation in rat brain: a pharmacological investigation.

Nitroglycerin is a nitric oxide donor which induces sustained expression of Fos protein, a marker of neuronal activation, in specific neuronal groups in the central nervous system. The mechanisms which underlie nitroglycerin-induced neuronal activation are elusive at this time, although a precise role has been suggested for the pool of neurons containing nitric oxide synthase as well as for catecholaminergic and peptidergic pathways. The aim of this study was to provide further details on the central effect of nitroglycerin by means of a pharmacological manipulation of nitroglycerin-induced neuronal activation with inhibitors of the nitric oxide synthase, modulators of the sympathetic drive and mediators of pain perception. Adult male Sprague-Dawley rats received L-NGnitro-arginine methyl ester, 7-nitro-indazole, ephedrine sulfate, indomethacin, capsaicin or vehicle before the subcutaneous injection of nitroglycerin (10 mg/kg b.w.). They were sacrificed 4 hr after nitroglycerin administration and brain sections were processed for immunocytochemical visualization of Fos. All the pharmacological treatments administered before injecting nitroglycerin selectively influenced Fos expression in the different brain nuclei. The data obtained suggest that nitroglycerin-induced neuronal activation is mediated by nociceptive and barosensitive mechanisms. Nitric oxide seems to represent the most important mediator of this phenomenon. The sympathetic system and prostaglandin synthesis are also likely to be involved.