The effect of hypoxia on nitric oxide production in the neonatal
pig lung.
Nelin, Leif D, Carol J Thomas, and Christopher A Dawson.
Department of Pediatrics and Physiology, Medical College of
Wisconsin, Milwaukee, WI and Research Service, Zablocki VAMC,
Milwaukee, WI
APStracts 2:0528H, 1995.
Nitric oxide (NO) synthase inhibitors are known to potentiate hypoxic
vasoconstriction suggesting that NO production during hypoxia
normally acts to attenuate the hypoxic response, and that hypoxia
might be associated with an alteration in NO production. To begin to
examine this hypothesis we studied four groups of isolated neonatal
pig lungs. In three groups of lungs, the accumulation of
nitrite/nitrate (NOx_) was measured in the recirculating perfusate.
One group (Cont) was ventilated with a control gas mixture (PO2 116
+/- 2 Torr), another group (Hypo) was ventilated with a hypoxic gas
mixture (PO2 52 +/- 2 Torr), and a third group was ventilated with
the control gas mixture but with N_-nitro-L-arginine methylester
(NAME) added to the perfusate (270 mg added to 250 ml perfusate).
Cont lungs had a stable perfusion pressure (Pa - Pv) during the
entire perfusion period, and both hypoxia and NAME significantly
increased Pa - Pv. NOx_ accumulated in the perfusate at an average
rate of 9.1 +/- 2.3 (SE) nmol/min in Cont, 3.7 +/- 0.8 nmol/min
(p<0.05 compared to control) in Hypo and 3.7 +/- 0.6 nmol/min
(p<0.05 compared to control) in NAME. In six lungs from the Cont
or Hypo groups, at the end of the 180 minute experimental period, the
response to hypoxia was measured before and after the addition of
NAME. Before NAME, hypoxia resulted in a 19 +/- 5% increase in Pa -
Pv, after NAME hypoxia resulted in a 95 +/- 18% increase in Pa - Pv
(p<0.02). In the fourth group of lungs, exhaled NO production
was measured during ventilation with the control gas mixture, with
the hypoxic gas mixture, and with the control gas mixture with NAME
added to the perfusate. The Pa - Pv also increased significantly with
both hypoxia and NAME in these lungs. The exhaled NO production also
decreased significantly with both hypoxia and NAME. These results
suggest that in this preparation there was continuous production of
NO, that was decreased by hypoxia or NAME. We conclude that hypoxia
decreases NO production in isolated neonatal pig lungs, but the
decrease in NO production is not the cause of hypoxic pulmonary
vasoconstriction. Also, it is not clear how the potentiation of the
hypoxic response by NO inhibitors and inhibition of NO production are
linked.
Received 8 August 1995; accepted in final form 9 November 1995.
APS Manuscript Number H744-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95