Pharmacological probes for a1 and a2 adenosine receptors in vivo in
the feline pulmonary vascular bed.
Neely, Constance Fisher, Idit Matot.
Department of Anesthesia, University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania, 19104
APStracts 2:0381H, 1995.
Under conditions of controlled pulmonary blood flow and constant left
atrial pressure, adenosine produces dose-dependent, tone-dependent
responses in the pulmonary vascular (PV) bed of intact-chest,
spontaneously breathing cats. The potency profile for adenosine
receptor agonists to produce vasoconstriction at low, baseline PV
tone is NECA >/= CGS 21680 >/= 2-CADO>/= R-PIA >/= CPA >
adenosine >> CV-1808. Following an increase in PV tone with
the use of an intralobar infusion of a thromboxane mimic, U46619, the
potency profile for adenosine receptor agonists to produce
vasodilation at elevated PV tone is 2-CADO >/= CV-1808 >/= CGS 21680
> R-PIA >/= adenosine. Selective A1 adenosine receptor
antagonists, XAC and DPCPX, significantly antagonize the
vasoconstrictor responses of adenosine and R-PIA, at low, baseline PV
tone while having less effect on the vasodilator responses of
adenosine, 2-CADO, and R-PIA at elevated PV tone. DPCPX antagonizes
the vasoconstrictor responses of CGS 21680 at low, baseline PV tone.
The nonselective A1, A2 adenosine receptor antagonist, BW A1433U
significantly antagonizes vasoconstrictor responses of R-PIA and
vasodilator responses of adenosine, 2-CADO, and R-PIA. These data
support that adenosine produces vasoconstriction at low, baseline PV
tone and vasodilation at elevated PV tone in the feline PV bed by
acting on A1 and A2 adenosine receptors, respectively. Compared to
the adenosine receptor agonists tested in this in vivo model, R-PIA
and CV 1808 are the most selective adenosine receptor agonists for A1
and A2 adenosine receptors, respectively, in the feline PV bed. R
-PIA, CV 1808, DPCPX, and XAC may be used in this in vivo model to
define the roles of A1 and A2 adenosine receptors in acute lung
injury and pathophysiological changes in the pulmonary vasculature
associated with pulmonary hypertension and edema formation in the
same animal model.
Received 29 September 1994; accepted in final form 9 August 1995.
APS Manuscript Number H880-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 15 September 1995.