Cardioprotection with inorganic nitrites
Végh Ágnes, Demeter-Haludka Vivien, Kovács Mária, Miskolczi Gottfried
Szegedi Tudományegyetem, Farmakológiai és Farmakoterápiai Intézet, Szeged
Organic nitrites and nitrates have been used for a long time in the treatment of coronary artery diseases. More recently it has turned out that these compounds not only improve the ischaemic changes, but they can also suppress the generation of ventricular arrhythmias, resulting from ischaemia and reperfusion. For example, we have evidence that increasing nitric oxide (NO) bioavailability by the administration of organic nitrites and nitrates, which are thought to act as NO donors, reduces the severity of arrhythmias that results from acute ischaemia and reperfusion in anaesthetized dogs. Although the precise mechanism of this antiarrhythmic effect of organic nitrites is not fully elucidated, it is almost certain that the protective effect can be associated with an increased nitric oxide bioavailability during ischaemia and reperfusion, and with the subsequent widespread regulative influence of nitric oxide on the various biological functions.
In the past decade it has become evident that the inorganic nitrite and nitrate, the natural metabolites of NO, which have been considered for a long time as inert molecules without further biological activity, may play an important physiological role in mediating the biological effects of nitric oxide. It has been recognised that these molecules can readily reduce back to NO, especially under reductive conditions, such as hypoxia or ischaemia, thus providing nitric oxide to the NO depleted tissues. This enzyme-independent NO formation might be particular important during ischaemia, when in the absence of oxygen, the NO production by nitric oxide synthase (NOS) enzymes becomes limited. Thus nitrite can serve as a fundamental natural store of NO that serves to maintain cardiac function under ischaemic conditions.
Our research group at the Department of Pharmacology and Pharmacotherapy of the Szeged University has a long interest in the exploration of the cardioprotective effects of nitric oxide. We are particularly interested in to examine the effects and the underlying mechanisms of nitric oxide on the ischaemia and reperfusion induced acute arrhythmias. Since Professor Julius Papp, a member of the Hungarian Academy of Sciences, during his chairmanship of our Department has been involved and mentored this research; we should like to tribute him on his 80th birthday by providing a summary of our current achievements, relating to the cardioprotective effects of inorganic nitrates.