Aspirin-stimulated nitric oxide production by neutrophils after acute myocardial ischemia in rabbits.
BACKGROUND
In recent studies, it has been hypothesized that the protective anti-ischemic effects of aspirin outweigh the effects of inhibition of platelet thromboxane A2 synthesis. Recently, we have found that the antiaggregating effects of aspirin significantly affect nitric oxide (NO) generation by neutrophils.


RESULTS
The present study used circulating neutrophils from myocardial ischemic rabbits to assess the effect of aspirin on the circulating neutrophil-derived NO production and, subsequently, on the modulation of platelet activation. Neutrophils were obtained after 60 minutes of coronary artery occlusion followed by 60 minutes of reperfusion. Sham-operated animals were used as controls. The results demonstrated that aspirin stimulated the production of NO by neutrophils obtained from both sham-operated rabbits and rabbits with myocardial ischemia. However, neutrophils isolated from animals with myocardial ischemia showed an enhanced ability to generate NO in the presence of aspirin. As a functional in vitro marker, we observed that neutrophils had a NO-dependent, platelet-antiactivating effect in the presence of aspirin. In the absence of aspirin, ischemic neutrophils did not modify platelet activation, even though they produced increased amounts of NO. An inhibitory role of superoxide anion on the neutrophil-related antiplatelet effect was suggested because superoxide dismutase induced significant platelet inhibition by myocardial ischemic neutrophils in the absence of aspirin.


CONCLUSIONS
Our results show that myocardial ischemia/reperfusion stimulates production of NO by circulating neutrophils, an effect that was enhanced in the presence of aspirin. These results suggest a novel interpretation of the protective effect of aspirin on myocardial ischemia damage.
López-Farré
A
A
Laboratorio de Nefrología-Hipertensión, Fundación Jiménez Díaz, Madrid, Spain.
Riesco
A
A
Digiuni
E
E
Mosquera
J R
JR
Caramelo
C
C
de Miguel
L S
LS
Millás
I
I
de Frutos
T
T
Cernadas
M R
MR
Montón
M
M
Alonso
J
J
Casado
S
S
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D009569:Nitric Oxide; D001241:Aspirin