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(Circulation. 2004;110:3573-3580.)
© 2004 American Heart Association, Inc.

Molecular Cardiology

Control of Plasma Nitric Oxide Bioactivity by Perfluorocarbons

Physiological Mechanisms and Clinical Implications

Olga Rafikova, MD; Elena Sokolova, MSc; Ruslan Rafikov, MSc; Evgeny Nudler, PhD

From the Department of Biochemistry, New York University Medical Center, New York, NY.

Correspondence to Dr Evgeny Nudler, New York University Medical Center, Department of Biochemistry, 550 First Ave, MSB #359, New York, NY 10016. E-mail evgeny.nudled{at}med.nyu.edu

Received May 21, 2004; revision received July 18, 2004; accepted August 2, 2004.

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).

Methods and 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 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, 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, 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.

Key Words: blood pressure • hemodynamics • nitric oxide • oxygen • fluorocarbons

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