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 nitrogly cerin possesses, besides its peripheral vasodilator effect, additional, puz zling biological activities. This organic nitrate compound provokes reflex cardiovascular activities via its interaction with the central sympathetic system. Its cerebrovascular e ffect, on the other hand, is probably mediated by the local release of neur opeptides, 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 spe cific headache attack in patients suffering from migraine. Because of its t emporal pattern and clinical characteristics, nitroglycerin-induced headach e cannot be solely ascribed to the a drug-induced vasorelaxation, The demonstration that systemic nitroglycerin administration activates a wi despread set of vegetative, nociceptive and neuroendocrine structures in th e 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 pr ovided information on the putative neurotransmitters and neurochemical mech anisms involved in nitroglycerin-induced neuronal activation. (C) 1999 Else vier Science Ltd. All rights reserved.