AJP - Heart and Circulatory Physiology, Vol 256, Issue 1 41-H46, Copyright © 1989 by American Physiological Society
Characterization of adenosine receptors in human pulmonary arteries
D. G. McCormack, B. Clarke and P. J. Barnes
Department of Thoracic Medicine, Cardiothoracic Institute, London, United Kingdom.
We have characterized the effects of adenosine, the A1-receptor agonist
N6-(L-2-phenylisopropyl)-adenosine (PIA) and the A2-receptor agonist
5'-(N-ethyl)-carboxamido-adenosine (NECA), in isolated human pulmonary
vessels. Fresh human lung tissue was obtained from nine patients, and small
pulmonary arteries (200-400 micron ID) were dissected and mounted in an
organ bath. The effects of the adenosine antagonist 8-phenyltheophylline
(8-PT) and endothelial denudation were also studied. Adenosine, NECA, and
PIA (1-300 microM) all caused a dose-dependent vasodilation with log EC30
values of -4.31, -4.31, and -3.53, respectively. 8-PT (10 microM) caused a
rightward shift of the adenosine dose-response curve, significantly
decreasing the effect of adenosine (pKB = 6.3). Mechanical removal of
endothelial cells had no significant effect on adenosine-mediated
vasodilation. We also compared the effects of adenosine on eight large
(7-10 mm ID) and eight small (200-400 micron ID) arteries and found no
significant difference in the sensitivity to adenosine between these
vessels. Our findings suggest that the pulmonary vasodilator effects of
adenosine in humans are mediated through A2 receptors that are localized to
vascular smooth muscle. Adenosine may function as a regulator of pulmonary
vascular tone in humans and may have therapeutic potential.
