Journal of Applied Physiology, Vol 67, Issue 3 1076-1080, Copyright © 1989 by American Physiological Society
Effect of fenoldopam on preconstricted isolated salt-perfused rat lungs
M. J. Polak, M. E. Knight, G. E. Gause, R. L. Bucciarelli and W. Drummond
Department of Pediatrics, University of Florida College of Medicine, Gainesville 32610.
Using an in situ isolated salt-perfused rat lung preparation, we
investigated the pulmonary vascular response to fenoldopam (a highly
selective dopamine (DA1) agonist) infused at six different doses ranging
from 0.1 to 10,000 micrograms/kg, during prostaglandin F2 alpha- (PGF2
alpha) induced pulmonary vasoconstriction. These experiments were repeated
after selective DA1-blockade with SCH 23390. Twelve experiments were
performed to evaluate the effect of fenoldopam on base-line hemodynamics.
Sixty experiments were performed after PGF2 alpha vasoconstriction. Thirty
lung preparations were pretreated with SCH 23390. PGF2 alpha was infused
into the pulmonary inflow catheter at 2.5 micrograms.kg-1.min-1 to give a
sustained rise in mean pulmonary arterial pressure (5.0 +/- 1.0 mmHg).
Fenoldopam, at doses of 0.1, 1, 10, 100, 1,000, or 10,000 micrograms/kg,
was injected into the pulmonary artery (n = 5 blocked and n = 5 unblocked
at each dose). Fenoldopam had no effect on hemodynamics in the absence of
PGF2 alpha. In the unblocked group, after PGF2 alpha vasoconstriction,
fenoldopam infusion resulted in a dose-dependent decrease in the mean
pulmonary arterial pressure with a dose-response curve characteristic for a
drug-receptor interaction [Response = -1.0 (log Dose) -1.6]. In the
DA1-blocked group after PGE2 alpha vasoconstriction, the dose-response
curve was shifted to the right but parallel to the unblocked group,
indicating competitive receptor blockade [Response -0.8 (log Dose) -0.05].
We conclude that vasodilatory DA1-receptors are responsible for the
observed results.
