Atp: the erythrocyte link to no and local control of the pulmonary
circulation.
Sprague, Randy S., Mary L. Ellsworth, Alan H. Stephenson, and Andrew
J. Lonigro.
Departments of Medicine and Pharmacological and Physiological
Science, Saint Louis University School of Medicine, St. Louis, MO
63104
APStracts 3:0414H, 1996.
Recently, we reported that rabbit red blood cells (RBCs) were required
for the expression of nitric oxide (NO) activity on pulmonary
vascular resistance (PVR) in rabbit lungs. Here, we investigate the
hypothesis that RBCs participate in the regulation of PVR via release
of adenosine triphosphate (ATP) in response to mechanical deformation
which, in turn, evokes vascular NO synthesis. We found that rabbit
and human RBCs, but not dog RBCs, release ATP in response to
mechanical deformation. To determine the contribution of this ATP to
NO synthesis and PVR, we compared the effects of human and dog RBCs
on pressure-flow relationships in isolated rabbit lungs. In the
presence of human RBCs, NG-nitro-L-arginine methyl ester (L-NAME, 100
[mu]M) produced a shift in the pressure-flow relationship consistent
with a reduction in vascular caliber. L-NAME had no effect in lungs
perfused with dog RBCs. These results suggest a unique mechanism for
control of PVR in rabbits and humans, whereby, release of ATP by RBCs
in response to mechanical deformation leads to stimulation of NO
synthesis which, in turn, modulates PVR.
Received 13 August 1996; accepted in final form 20 September
1996.
APS Manuscript Number H743-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996