[Bile salts and spontaneous release of PGI2, TxA2 and fVIII from cultured human endothelial cells].
A normally functioning vascular endothelium is required for vascular tone modulation and blood fluidity. Systemic and local circulatory and coagulation alterations, even to the point of renal failure, may be observed in obstructive jaundice; bile salts are included among the potential pathogenetic factors. To assess the effects of taurocholic acid, glycocholic acid, and cholic acid on the integrity and properties of the endothelium, cultured human endothelial cells (HUVEC) were studied. Taurocholic and glycocholic acids (up to 2000 mumoles/L) did not exhibit any significant effect on 51Cr release from HUVEC after 6 h incubation. Following HUVEC exposure to 2000 mumoles/L of the unconjugated compound, cholic acid, a significant discharge of the radiolabel and LDH leakage in the supernatant were observed, to some extent prevented by the presence of human plasma or albumin (physiologic carrier). Prostacyclin spontaneous release from HUVEC was significantly depressed by both taurocholic and glycocholic acid; the action was related to bile salt concentration (200-1000 mumoles/L) and to the time of exposure (1 to 24 h); the reduced production of PGI2 was demonstrated to be reversible. Conversely, spontaneous TxA2 generation and fVIII release were not affected by the presence of bile salts in culture medium. Previous investigations showed that experimental obstructive jaundice could impair prostacyclin release from rat aortic tissue. The same effect was also demonstrated after in vitro exposure of the vessel wall to jaundiced serum and bile salts alone; furthermore, bile salts exert toxic effects on the integrity of several cells and impair the prostaglandin system of different tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcamuggi
G
G
Clinica Medica Generale III, Università degli Studi di Torino.
Lanzio
M
M
Babini
G
G
Martini
S
S
Anfossi
G
G
Emanuelli
G
G
D001647:Bile Acids and Salts / Q000494:pharmacology*; D002478:Cells, Cultured; D003470:Culture Media; D004727:Endothelium / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D005169:Factor VIII / Q000378:metabolism*; D006801:Humans; D013928:Thromboxane A2 / Q000378:metabolism*; D013997:Time Factors
D001647:Bile Acids and Salts; D003470:Culture Media; D013928:Thromboxane A2; D005169:Factor VIII; D011464:Epoprostenol
Sali biliari e rilascio spontaneo di PGI2, TxA2 e fVIII dalle cellule endoteliali umane in coltura.