Endogenous nitroxyl (HNO) production in a normal biological system and its role in platelet function.

POZNER, ROBERTO G; DOCTOROVICH, Y; MACCAFERRO, M.C.; SUAREZ, SEBASTIAN; MARTI, MARCELO A.; DOCTOROVICH F; SCHATTNER, MIRTA

Londres

Congreso; ISTH 2022 Congress; 2022

ISTH

Background:Platelet inhibition is focus of numerous investigations. Although several inhibitors are widely used, HNO (a reduced form of NO) is raising a great clinical interest. HNO shares vasodilatory properties with NO, but also showed increased muscle contractility, acceleration of ventricular relaxation and decrease in cardiac load. These data come from the use of HNO-releasing drugs, however, it is unknown if this gasomediator can be synthesized endogenously by platelets.AIM:In this study, we evaluated the generation of HNO by platelets (PRP) and its impact on functional responses.Methods:HNO production was quantified in real-time by two experimental strategies: detection of spectral changes of a porphyrin of Mn(III), and current changes using a high sensitivity selective electrochemical sensor -based on a porphyrin of Co(II)-. The concentration of HNO was estimated from a calibration curve made with Angeli´s salt (Fig.1A).Fibrinogen binding and P-selectin expression were evaluated by cytofluorimetry.Results:Stimulation of platelets with classical agonist TRAP, ADP or arachidonic acid (AA) promoted the generation of HNO (Fig.1B, n=5, p