Adenosine a1 and a2 receptors mediate tone-dependent responses in
the feline pulmonary vascular bed.
Cheng, David Y., Bracken J. Dewitt, Fumio Suzuki, Constance F. Neely,
and Philip J. Kadowitz.
Department of Pharmacology, Tulane University School of Medicine,
New Orleans, Louisiana 70112; Department of Anesthesiology,
University of Pennsylvania School of Medicine, Philadelphia,
Pennsylvania; Pharmaceutical Research Labs, Kyowa Hakko Co., Ltd.,
1188 Shimotogari, Nagaizumi-cho, Schizuoka 411 Japan
APStracts 2:0271H, 1995.
Adenosine produces tone-dependent responses in the feline pulmonary
vascular bed; however, the adenosine receptor subtype mediating
responses to the nucleoside has not been determined. The present
study was undertaken to investigate the adenosine receptor subtypes
mediating tone-dependent responses in the pulmonary vascular bed of
the intact-chest cat. Intralobar injections of adenosine, ATP, and
analogs under low resting-tone conditions caused dose-related
increases in lobar arterial pressure; and in terms of relative
vasoconstrictor activity, the order of potency was [alpha],[beta]
-methylene ATP ([alpha],[beta]-metATP) > N6-cyclopentyladenosine
(CPA) > ATP > adenosine. Increases in lobar arterial
pressure under low-tone conditions in response to adenosine, ATP, and
CPA, an adenosine A1 receptor agonist, were reduced by KW3902, an
adenosine A1 receptor antagonist, and; whereas, KW3902 and
meclofenamate had no effect on responses to [alpha],[beta]-metATP,
norepinephrine, serotonin, or angiotensin II. Under elevated-tone
conditions, intralobar injections of adenosine, ATP, and analogs
caused dose-related decreases in lobar arterial pressure; and in
terms of relative vasodilator activity, adenosine was 10-fold less
potent than 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), an A2
receptor agonist, and ATP. Following administration of KF17837, an A2
receptor antagonist, vasodilator responses to adenosine and CPCA were
reduced whereas responses to ATP, isoproterenol, DEA-NO, lemakalim,
and bradykinin were not changed. The decreases in lobar arterial
pressure in response to adenosine were not attenuated by Nw-nitro-L
-arginine benzyl ester, methylene blue, or U37883A. These results
suggest that vasoconstrictor responses to adenosine under low-tone
conditions are mediated by A1 receptors and the release of
vasoconstrictor prostanoids, and that under elevated-tone conditions
vasodilator responses are mediated by A2 receptors but do not involve
the release of nitric oxide, the activation of soluble guanylate
cyclase, or of K+ATP channels.
Received 17 November 1994; accepted in final form 8 June 1995.
APS Manuscript Number H1028-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 11 July 1995.