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Prostacyclin biosynthesis and reduced 5‐HT uptake after complement‐induced endothelial injury in the dog isolated lung
Author(s) -
Bult Hidde,
Heiremans Jose J.,
Herman Arnold G.,
Malcorps Christiane M.A.,
Peeters Frank A.M.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11464.x
Subject(s) - prostacyclin , medicine , endocrinology , biosynthesis , prostaglandin , thromboxane , endothelial stem cell , endothelium , thromboxane a2 , lung , chemistry , zymosan , biology , platelet , biochemistry , enzyme , in vitro
1 Pulmonary prostacyclin (PGI 2 ) biosynthesis was evaluated in relation to endothelial integrity before and after complement activation in isolated plasma‐perfused lung lobes of the dog. 2 The plasma was activated with zymosan (ZAP, n = 4), yeast cells (YAP, n = 4) or yeast with 3 μ m indomethacin (Indo + YAP, n = 3). Immunoreactive 6‐oxo‐prostaglandin F 1α (i‐6‐oxo‐PGF 1α ) and thromboxane B 2 (iTXB 2 ) were measured to monitor PGI 2 and TXA 2 biosynthesis. 3 The kinetic parameters K m and V max of 5‐hydroxytryptamine (5‐HT) uptake were calculated on the basis of multiple indicator diffusion data to evaluate endothelial integrity. 4 YAP and ZAP induced a biphasic increase of the arterial perfusion pressure. The immediate pressure peak was partly mediated by TXA 2 and the TXB 2 was subsequently cleared by the lung. 5 The apparent V max of 5‐HT uptake remained constant throughout the experiment. Thus, complement activation did not affect the number of endothelial 5‐HT carrier sites available to the perfusate. 6 The apparent K m of 5‐HT uptake was enhanced in 9 lungs exposed to activated plasma complement for 20 min. This decreased affinity for 5‐HT probably reflects endothelial injury. It was transient as the apparent K m had returned to the baseline value after 60 min. 7 PGI 2 clearance and biosynthesis were virtually absent in the control period. PGI 2 formation increased drastically after infusion of ZAP or YAP and was proportional to the endothelial injury expressed as elevated K m or pulmonary oedema. Thus, PGI 2 biosynthesis might be a marker of severe endothelial distress.