Airway and vascular effects of 8-epi-prostaglandin F2 alpha in isolated perfused rat lung.
The effects of 8-epi-prostaglandin (PG) F2 alpha, a recently discovered noncyclooxygenase free radical-catalyzed product of arachidonic acid, on pulmonary vascular and airway tone, its potency, and its mechanism of action were studied. Progressively increasing bolus doses (1.0, 5.0, 10.0, and 20.0 micrograms) of 8-epi-PGF2 alpha were injected into the pulmonary artery catheter of 18 isolated rat lungs, and a single dose (40.0 micrograms) was injected into 7 additional rat lungs. The lungs were perfused with Krebs-Henseleit buffer solution containing 3% bovine serum albumin at 50 ml.kg-1.min-1 during ventilation with 21% O2-5% CO2-74% N2. 8-Epi-PGF2 alpha caused rapid pulmonary vascular and airway constrictor responses, which were followed by a gradual return over 10 min to baseline levels. Double vascular occlusion at peak rise in pulmonary arterial pressure (Ppa) revealed a 28% increase in arterial resistance. The rise in Ppa with 20 micrograms of 8-epi-PGF2 alpha was approximately twofold greater than with 20 micrograms of the cyclooxygenase-derived prostaglandin PGF2 alpha. The addition of 100 microM N-nitro-L-arginine, a blocker of endothelium-derived relaxing factor, in the perfusate potentiated the rise in Ppa by 244%. Injection of 40 micrograms of rat atrial natriuretic factor at peak response to 20 micrograms of 8-epi-PGF2 alpha accelerated the return to baseline Ppa, resistance to airflow across the lung, and dynamic lung compliance values.(ABSTRACT TRUNCATED AT 250 WORDS)
Kang
K H
KH
Center for Lung Research, Vanderbilt University, Nashville, Tennessee 37232.
Morrow
J D
JD
Roberts
L J
LJ
Newman
J H
JH
Banerjee
M
M
D000399:Air Pressure; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects*; D008170:Lung Compliance / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects; D019335:Nitroarginine; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D015656:Respiratory Mechanics / Q000187:drug effects*; D013990:Tidal Volume / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; D019335:Nitroarginine; C075750:8-epi-prostaglandin F2alpha; D009320:Atrial Natriuretic Factor; C045749:SQ 29548; D001120:Arginine; D015237:Dinoprost