Control of plasma nitric oxide bioactivity by perfluorocarbons - Physiological mechanisms and clinical implications

Article

关键词: S-NITROSOTHIOLS;    BLOOD;    OXYGEN;    NITROSOHEMOGLOBIN;    NITROSYLATION;    NITROSATION;    HEMOGLOBIN;    REDUCTION;    KINETICS;    EMULSION;   

DOI  :  10.1161/01.CIR.0000148782.37563.F8

来源: SCIE

【 摘 要 】

Background - Perfluorocarbons (PFCs) are promising blood substitutes because of their chemical inertness and unparalleled ability to transport and upload O-2 and CO2. Here, we report that PFC emulsions also efficiently absorb and transport nitric oxide (NO). Methods and Results - Accumulation of NO and O-2 in PFC micelles results in rapid NO oxidation and generation of reactive NOx species. Such micellar catalysis of NO oxidation leads to formation of vasoactive S-nitrosothiols (RSNO) in vitro and in vivo as detected electrochemically. The efficiency of PFC-mediated S-nitrosation depends on the amount of PFC in aqueous solution. The optimal PFC concentration that produced the maximum level of RSNO was approximate to1% (vol/vol). Larger PFC amounts were progressively less efficient in generating RSNO and functioned simply as NO sink. These results explain the characteristic hemodynamic effects of PFCs. Intravenous bolus application of PFC (0.14 g/kg, approximate to1% vol/vol) to Wistar-Kyoto rats decreased mean arterial pressure significantly (-10 mm Hg over 40 minutes). PFC-induced hypotension could be further stimulated (-17 mm Hg over 140 minutes) by exogenous thiols (cysteine and glutathione). In contrast, a larger amount of PFC (1 g/kg, approximate to7% vol/vol) exhibited a strong hypertensive effect (11 mm Hg over 40 minutes). Conclusions - The present study reveals a physiologically significant pool of endogenous plasma NO and underscores the crucial role of the circulating hydrophobic phase in modulating its bioactivity. The results also establish PFC as a conceptually new pharmacological tool for various cardiovascular complications associated with NO imbalance.

【 授权许可】

Free