[Perspectives of pharmacological correction of nitroxidergic vasorelaxation in subarachnoidal hemorrhage].
Subarachnoidal hemorrhage (SAH) causes cerebrovascular endothelial dysfunction that leads to impaired nitrosidergic vasorelaxation, delayed vasospasm, and cerebral ischemia. The purpose of the present review is to study the current potentialities of drug action on the system of generation of and the functional activity of nitric oxide (NO) in order to prevent and treat cerebral ischemic complications due to SAH. A scheme of the biosynthesis of NO and the mechanism of nitroxidergic vasorelaxation is presented. According to the direction of the action of a pharmacological agent (the biochemical target), the authors identified six groups of methods: 1) regulation of the level of a substrate; 2) activation of inhibition of NO-synthase enzymes; 3) action on the level of cofactors; 4) that on the metabolism of endogenous NO; 5) administration of exogenous NO; 6) action of the effector system of NO/cGMF. They show that not always an individual method is shown to be rather effective and safe for the treatment of patients after SAH. A concept of the combined use of methods from different groups for the synergism and potentiation of their impact on nitroxidergic vasorelaxation with a minimum of adverse effects is proposed.
Karpiuk
V B
VB
Shubich
M G
MG
D001120:Arginine / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology*
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP