Evaluation of prostaglandin F2 alpha and prostacyclin interactions in the isolated perfused rat lung.
To characterize the interactions between prostaglandin F2 alpha and prostacyclin in controlling tone in the pulmonary circulation, isolated rat lungs were ventilated, perfused with blood, and subjected to challenge by prostaglandin F2 alpha in increasing doses. The pulmonary resistance was evaluated using occlusion techniques that separate the resistance into segments of large and small arteries and veins. The total vascular compliance was evaluated using outflow occlusion. Resistance increased after prostaglandin F2 alpha, and this resistance change was primarily in the small artery segment. The maximum resistance increase by prostaglandin F2 alpha (Rmax,PGF2 alpha), calculated from the Michaelis-Menton equation, was 16.6 +/- 3.6 cmH2O.l-1.min.100 g-1 for total vascular resistance with a concentration required to produce 50% Rmax (K0.5) of 5.26 +/- 3.57 nM. The Rmax,PGF2 alpha for small artery resistance was 13.5 +/- 2.4 cmH2O.l-1.min.100 g-1 with a K0.5 of 2.35 +/- 1.57 nM. The vascular compliance decreased during vasoconstriction by prostaglandin F2 alpha, and the maximum decrease in compliance (Cmin,PGF2 alpha) was -0.43 +/- 0.12 ml/cmH2O with a K0.5 of 2.84 +/- 2.99 nM. At each dose of prostaglandin F2 alpha, prostacyclin was administered in increasing doses to reverse the vasoconstriction caused by prostaglandin F2 alpha. For each concentration of prostaglandin F2 alpha, prostacyclin almost completely reversed the resistance increases and approximately one-half the compliance decrease. The maximum change in vascular resistance or compliance produced by prostacyclin was dependent on the dose of prostaglandin F2 alpha; yet the K0.5 for prostacyclin was within the picomolar range for all doses of prostaglandin F2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
Barnard
J W
JW
Department of Physiology, College of Medicine, University of South Alabama, Mobile 36688.
Ward
R A
RA
Taylor
A E
AE
D000818:Animals; D015237:Dinoprost / Q000008:administration & dosage* / Q000502:physiology; D004347:Drug Interactions; D011464:Epoprostenol / Q000008:administration & dosage* / Q000502:physiology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D011982:Receptors, Prostaglandin; D015237:Dinoprost; D011464:Epoprostenol