Differential influence of arachidonic vs. eicosapentaenoic acid on experimental pulmonary hypertension.
The impact of the 2- and 3-series prostanoid precursors arachidonic acid (AA) and eicosapentaenoic acid (EPA) on experimental pulmonary hypertension was investigated. The model of buffer-perfused rabbit lungs was stimulated by infusion of Escherichia coli hemolysin (HlyA), which is known to provoke sustained thromboxane (Tx)-mediated pulmonary hypertension. Release of di- and trienoic Tx into the recirculating perfusate was quantified by a post-high-performance liquid chromatography enzyme-linked immunosorbent assay technique. HlyA at 0.08 hemolytic unit/ml caused a sustained rise in pulmonary arterial pressure (PAP; maximum increase 14 +/- 2 mmHg) accompanied by progressive TxB2 liberation (maximum perfusate concn 33 +/- 4 pg/ml, baseline < 2 pg/ml). Between 5 and 30 nM, AA provoked a transient monophasic rise in PAP (maximum pressor response 1.5-15 mmHg) and concomitant TxB2 release (peak concn 2-30 pg/ml). Simultaneous administration of HlyA and AA exhibited additive effects with regard to mediator release and pressor responses. EPA at 200-2,000 nM caused a transient rise in PAP similar to that provoked by 5-30 nM AA (maximum pressor response 3-18 mmHg). This was accompanied by liberation of TxB2 (peak concn 16 +/- 5 and 28 +/- 4 pg/ml after 1,000 and 2,000 nM EPA) and TxB3 (peak concn 9 +/- 4 and 30 +/- 3 pg/ml). Combined application of HlyA and EPA resulted in approximate addition of the TxB2 release reaction to each single compound, and TxB3 liberation more than doubled (maximum concn 59 +/- 12 pg/ml). The pressor responses to HlyA-EPA (200-2,000 nM) did not, however, surpass those to HlyA-AA (5-30 nM).(ABSTRACT TRUNCATED AT 250 WORDS)
Grimminger
F
F
Department of Internal Medicine, Justus-Liebig University, Giessen, Germany.
Wahn
H
H
Kramer
H J
HJ
Stevens
J
J
Mayer
K
K
Walmrath
D
D
Seeger
W
W
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004926:Escherichia coli; D005260:Female; D006460:Hemolysin Proteins / Q000633:toxicity; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008297:Male; D011188:Potassium / Q000097:blood; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000378:metabolism; D013931:Thromboxanes / Q000031:analogs & derivatives*
D006460:Hemolysin Proteins; D013931:Thromboxanes; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015118:Eicosapentaenoic Acid; D011188:Potassium; C039158:thromboxane B3