Effect of fenoldopam on preconstricted isolated salt-perfused rat lungs.
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.
Polak
M J
MJ
Department of Pediatrics, University of Florida College of Medicine, Gainesville 32610.
Knight
M E
ME
Gause
G E
GE
Bucciarelli
R L
RL
Drummond
W
W
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D018818:Fenoldopam; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D015237:Dinoprost; D018818:Fenoldopam