Control of plasma nitric oxide bioactivity by perfluorocarbons: physiological mechanisms and clinical implications.
BACKGROUND
Perfluorocarbons (PFCs) are promising blood substitutes because of their chemical inertness and unparalleled ability to transport and upload O2 and CO2. Here, we report that PFC emulsions also efficiently absorb and transport nitric oxide (NO).


RESULTS
Accumulation of NO and O2 in PFC micelles results in rapid NO oxidation and generation of reactive NO(x) 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 approximately 1% (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, approximately 1% 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, approximately 7% 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.
Rafikova
Olga
O
Department of Biochemistry, New York University Medical Center,New York, NY 10016, USA.
Sokolova
Elena
E
Rafikov
Ruslan
R
Nudler
Evgeny
E
D000818:Animals; D001692:Biological Transport; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004563:Electrochemistry; D005466:Fluorocarbons / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D008823:Micelles; D009569:Nitric Oxide / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011921:Rats, Inbred WKY; D026403:S-Nitrosothiols / Q000097:blood / Q000737:chemistry
D001802:Blood Substitutes; D005466:Fluorocarbons; D008823:Micelles; D026403:S-Nitrosothiols; D009569:Nitric Oxide