Dipyridamole, a cgmp phosphosdiesterase inhibitor, causes pulmonary
vasodilation in the ovine fetus .
Ziegler, James W., D. Dunbar Ivy, Jonathan J. Fox, John P. Kinsella,
William R. Clarke, Steven H. Abman.
Departments of Pediatrics, Sections of Cardiology, Neonatology, and
Pulmonary Medicine, The Children's Hospital and the University of
Colorado School of Medicine, Denver, CO 80262; and the Departments of
Anesthesiology and Pediatrics, University of Washington School of
Medicine, Seattle, WA 98195
APStracts 2:0165H, 1995.
Endogenous nitric oxide (NO) modulates fetal pulmonary vascular tone
by stimulating cyclic guanosine monophosphate (cGMP) production in
vascular smooth muscle. Since cGMP is hydrolyzed and inactivated by
phosphodiesterase enzymes, we evaluated the hemodynamic effects of 2
cGMP-specific phosphodiesterase (PDE5) inhibitors, dipyridamole and
zaprinast, in the near-term, chronically-prepared ovine fetus. Brief
(10 minute) intrapulmonary infusions of dipyridamole caused dose
-dependent increases in left pulmonary artery flow (Qp) and decreases
in left pulmonary arterial resistance (PVR) which persisted for more
than 40 minutes after termination of the infusion. Prolonged (2 hour)
infusions of dipyridamole caused sustained pulmonary vasodilation
throughout the infusion period. To compare the hemodynamic effects of
dipyridamole with another PDE5 antagonist, zaprinast, we studied the
responses to equimolar doses of both agents in 4 fetuses. Zaprinast
caused dose-dependent pulmonary vasodilation that was equivalent to
that noted with equimolar doses of dipyridamole. To determine whether
adenosine is involved with dipyridamole-induced pulmonary
vasodilation, we compared the hemodynamic response to dipyridamole
before and after administration of the potent adenosine receptor (P1)
antagonist, 8-phenyltheophylline (8-PT). Pretreatment with 8-PT
markedly attenuated adenosine-induced pulmonary vasodilation but had
no effect on the hemodynamic response to dipyridamole. We conclude
that cGMP-specific phosphodiesterase activity is important in
regulating fetal pulmonary vascular tone. In addition, dipyridamole
administration causes dose-dependent pulmonary vasodilation which is
equivalent to zaprinast and not primarily due to its effects on
adenosine. We speculate that dipyridamole may be useful as a
pulmonary vasodilator, either alone or in combination with cGMP
-dependent dilators such as inhaled NO.
Received 6 December 1994; accepted in final form 22 February
1995.
APS Manuscript Number H1070-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 2 May 1995.