Blood, Vol. 93 No. 1 (January 1), 1999:
pp. 333-340
Nitric Oxide-Mediated Augmentation of Polymorphonuclear Free Radical
Generation After Hypoxia-Reoxygenation
Sonia Sethi,
Mahendra Pratap Singh, and
Madhu Dikshit
From the Pharmacology Division, Central Drug Research Institute,
Lucknow, India.
Polymorphonuclear leukocytes (PMNLs), nitric oxide (NO), calcium,
and free radicals play an important role in hypoxia/ischemia and
reoxygenation injury. In the present study, NO donors, sodium nitroprusside (SNP), and diethylamine-NO
(DEA-NO) at low concentrations (10 and 100 nmol/L)
potentiated, while higher (10 µmol/L to 10 mmol/L) concentrations
inhibited free radical generation response in the rat PMNLs. Free
radical generation response was found to be significantly augmented
when hypoxic PMNLs were reoxygenated (hypoxia-reoxygenation
[H-R]). This increase in free radical generation after
reoxygenation or SNP (10 nmol/L) was blocked in the absence of
extracellular calcium. SNP (10 nmol/L) or H-R-mediated increases in
the free radical generation were prevented by the pretreatment of PMNLs
with NO scavenger (hemoglobin), the polyadenine diphosphate (ADP)-ribosylation synthase inhibitor (benzamide) or the calcium channel antagonist (felodipine). A significant augmentation in the
nitrite and intracellular calcium levels was observed during hypoxia.
Hemoglobin pretreatment also blocked the increase in intracellular
calcium levels due to SNP (10 nmol/L) or hypoxia. Thus, increased
availability of NO during SNP treatment or H-R, may have led to an
ADP-ribosylation-mediated increase in intracellular calcium, thereby
increasing the free radical generation from the rat PMNLs.
