The effects on the central nervous system of nitroglycerin--putative mechanisms and mediators

Nitroglycerin is an organic nitrate that has been used as a vasodilator in the treatment of cardiac diseases for over a century. Only recently it has been demonstrated that the vasodilator effect of this drug depends upon the formation of nitric oxide in the blood vessel wall. However, clinical and research data gathered during the last decades have suggested that nitroglycerin possesses, besides its peripheral vasodilator effect, additional, puzzling biological activities. This organic nitrate compound provokes reflex cardiovascular activities via its interaction with the central sympathetic system. Its cerebrovascular effect, on the other hand, is probably mediated by the local release of neuropeptides. The direct application of nitroglycerin onto brain nuclei causes a prompt increase in the neuronal discharge rate. From a neurological point of view, nitroglycerin consistently induces a specific headache attack in patients suffering from migraine. Because of its temporal pattern and clinical characteristics, nitroglycerin-induced headache cannot be solely ascribed to the a drug-induced vasorelaxation. The demonstration that systemic nitroglycerin administration activates a widespread set of vegetative, nociceptive and neuroendocrine structures in the central nervous system seems to further support the occurrence of central mechanisms in the biological activity of nitroglycerin. Double labeling immunocytochemical and neuropharmacological studies have provided information on the putative neurotransmitters and neurochemical mechanisms involved in nitroglycerin-induced neuronal activation.