Effect of inhibition of nitric oxide synthesis on the diaphragmatic
microvascular response to hypoxia.
Ward, Michael E.
Divisions of Critical Care and Pulmonary Medicine, Royal Victoria
Hospital, McGill University, Montreal, Quebec, Canada
APStracts 3:0280A, 1996.
The purpose of this study was to determine the effect of inhibition of
nitric oxide (NO) release on the diaphragmatic microvascular
responses to hypoxia. In [alpha]-chloralose anaesthetized mongrel
dogs, the microcirculation of the vascularly isolated, ex-vivo, left
hemidiaphragm was studied by intravital microscopy. The diaphragm was
pump perfused with blood diverted from the femoral artery through a
series of membrane oxygenators. The responses to supramaximal
concentrations of sodium nitroprusside (SNP), moderate hypoxia
(phrenic venous PO2=27 mmHg) and severe hypoxia (phrenic venous PO2 =
15 mmHg) were recorded before and after infusion of NG-nitro-L
-arginine (LNA, 6 x 10-4M) into the phrenic circulation for 20
minutes. Under control conditions diaphragmatic blood flow was 12.4
+/- 1.1 ml/min/100g. Diaphragmatic blood flows recorded during
moderate and severe hypoxia were 15.6 +/- 1.2 ml/min/100g and 24.3
+/- 1.5 ml/min/100g, respectively (p<0.05, for both, compared
with control). Treatment with LNA reduced diaphragmatic blood flow to
9.6 +/- 0.8 ml/min/100g (p<0.05) under control conditions and
caused arteriolar vasoconstriction to a degree which was dependent on
vessel size (ie: larger vessels constricted more than smaller
vessels). LNA eliminated the increase in blood flow during moderate
hypoxia and inhibited arteriolar dilation by an amount which was
related to vessel size (ie: dilation of larger vessels inhibited more
than smaller vessels). Inhibition of NO synthesis had no effect on
the increase in diaphragmatic blood flow (23.6 +/- 1.9 ml/min/100g,
p>0.05 compared with that during severe hypoxia before treatment
with LNA) or arteriolar diameters during severe hypoxia. Nitric oxide
release plays a role in the diaphragmatic vascular response to
hypoxia, but this role is limited to dilation of larger arterioles
during hypoxia of moderate severity.
Received 12 September 1995; accepted in final form 6 June 1996.
APS Manuscript Number A997-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96