Inhaled nitric oxide does not alter endotoxin-induced nitric oxide
synthase activity during rat lung perfusion.
Kurrek, Matt M., Leticia Castillo, Kenneth D. Bloch, Steven R.
Tannenbaum, and Warren M. Zapol.
Departments of Anaesthesia (WMZ), Pediatrics (LC) and the
Cardiovascular Research Center, General Medical Services (KDB),
Massachusetts General Hospital, the Department of Anesthesia (MMK),
Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts;
and the Department of Chemistry and Toxicology (SRT), Massachusetts
Institute of Technology, Cambridge, Massachusetts
APStracts 2:0316A, 1995.
Nitric oxide has been demonstrated to decrease its own synthesis in
tissue preparations. We tested the hypothesis that endogenous NO
synthesis induced by LPS would be decreased by exogenous NO during
isolated lung perfusion. Methods: Rats were pretreated with either
saline or LPS 48 hours prior to lung harvest. Endogenous NOS activity
was measured as L-[14C]arginine to L-[14C]citrulline conversion
during 90 minutes of perfusion. NO (100 ppm) was added to the
ventilating gas during perfusion of lungs from one group of control
or LPS-treated rats. A second group of control or LPS-treated rats
was exposed chronically to 100 ppm NO for the 48 h prior to lung
harvest, in addition to receiving NO 100 ppm added to the ventilating
gas during lung perfusion. Results and Conclusion: Conversion of L
-[14C]arginine to L-[14C]citrulline was minimal in control lungs and
increased in response to LPS-pretreatment. NO added to the
ventilating gas for the 90 min of ex-vivo perfusion did not alter the
rate of L-[14C]citrulline production. In-vivo exposure to 100 ppm NO
for 48h did not alter the induction of iNOS activity as measured
during ex-vivo lung perfusion. This indicates that inhaled NO does
not exert negative feedback inhibition on iNOS in the ex-vivo rat
lung.
Received 30 September 1994; accepted in final form 27 February
1995.
APS Manuscript Number A1013-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.