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Cited by 263

The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.

Peroxynitrite inhibits leukocyte-endothelial cell interactions and protects against ischemia-reperfusion injury in rats.

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Lefer, D J, Scalia, R, Campbell, B, Nossuli, T, Hayward, R, Salamon, M, Grayson, J, Lefer, A M·1997·Journal of Clinical Investigation

Abstract

Peroxynitrite (ONOO-) anion, formed by the interaction of superoxide with nitric oxide (NO), has previously been implicated as a cytotoxic agent. However, the effects of this free radical species on neutrophil (PMN)-endothelial cell interactions is largely unknown. We investigated the direct actions of ONOO- on PMN adhesion to endothelial cells in vitro and in vivo, as well as the effects of ONOO- on PMN-mediated myocardial ischemia-reperfusion injury. In vitro, peroxynitrite (100-1,000 nM) inhibited the adhesion of rat PMNs to the endothelium of isolated thrombin- or H2O2-stimulated rat mesenteric artery (P < 0.01 vs. thrombin or H2O2 alone). In vivo, in the rat mesentery, thrombin (0.5 U/ml) or N(G)-nitro-L-arginine-methyl ester (50 microM) significantly increased venular leukocyte rolling and adherence, which were also significantly (P < 0.01) attenuated by ONOO (800 nM) accompanied by reduced P-selectin expression on the endothelial cell surface. Isolated perfused rat hearts were subjected to global ischemia and reperfusion with rat PMNs (10(8) cells), which resulted in profound cardiac depression (i.e., a marked reduction in left ventricular developed pressure and maximal rate of development of left ventricular pressure). Infusion of ONOO- reversed the myocardial contractile dysfunction of ischemic-reperfused rat hearts to near baseline levels, and markedly attenuated the accumulation of PMNs in the postischemic heart. The present study provides strong evidence that nanomolar concentrations of ONOO- both inhibit leukocyte-endothelial cell interactions and exert cytoprotective effects in myocardial ischemia-reperfusion injury. Furthermore, our results suggest that the inhibition of P-selectin expression by peroxynitrite is a key mechanism of the modulatory actions of ONOO- on leukocyte-endothelial cell interactions.

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Metadata

Authors
Lefer, D. J., Scalia, R., Campbell, B., Nossuli, T., Hayward, R., Salamon, M., Grayson, J., & Lefer, A. M.
Venue
Journal of Clinical Investigation
Published
1997-02-15
Volume
99
Issue
4
Pages
684-691
ISSN
0021-9738 (ISSN-L)
OpenAlex
W2079043570
Cited by
263
References
50
FWCI
16.84
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Peroxynitrite inhibits leukocyte-endothelial cell interactions and protects against ischemia-reperfusion injury in rats. https://app.cochat.ai/papers/10.1172/jci119212
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Lefer, D. J., Scalia, R., Campbell, B., Nossuli, T., Hayward, R., Salamon, M., Grayson, J., & Lefer, A. M. (1997). Peroxynitrite inhibits leukocyte-endothelial cell interactions and protects against ischemia-reperfusion injury in rats. Journal of Clinical Investigation. https://doi.org/10.1172/jci119212

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