From the Howard Hughes Medical Institute (J.S.S.) and Department of
Medicine (J.R.P., J.S.S.) and Division of Pulmonary and Cardiovascular
Medicine (R.V.S., J.S.S.), Duke University Medical Center, Durham, NC.
Correspondence to Jonathan S. Stamler, MD, Duke University Medical Center, Howard Hughes Medical Institute, Room 321 MSRB, Box 2612, Durham, NC 27710.
Background—Nitric oxide (NO) and
related molecules are thought to inhibit human platelet aggregation
by raising levels of cGMP.
Methods and Results—Both oxidative stress (reactive oxygen
species) and hemoglobin (Hb) seem to oppose NO effects. A major
fraction of NO in the blood is bound to thiols of Hb, forming
S-nitrosohemoglobin (SNO-Hb), which releases the NO
group on deoxygenation in the microcirculation. Here we
show that (1) both cell-free and intraerythrocytic SNO-Hb (SNO-RBC)
inhibit platelet aggregation, (2) the oxidation state of the hemes
in Hb influences the response—SNO-metHb (which is functionally similar
to SNO-deoxyHb) has greater platelet inhibitory effects
than SNO-oxyHb, and (3) the mechanism of platelet inhibition by
SNO-Hb is cGMP independent.
Conclusions—We suggest that the RBC has evolved a means to
counteract platelet activation in small vessels and the
proaggregatory effects of oxidative stress by forming SNO-Hb.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Cell-Free and Erythrocytic S-Nitrosohemoglobin Inhibits Human Platelet Aggregation
Key Words: S-nitrosohemoglobin • nitric oxide • platelets
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