Importance of secondary TXA2 release in mediating of endothelin-1 induced bronchoconstriction and vasopressin in the guinea-pig.

The i.v. bolus application of 1 nmol/kg endothelin-1 (ET-1) in anaesthetized and ventilated guinea-pigs caused an increase in mean arterial blood pressure (BP) and a bronchoconstriction.

PAF-induced death in NMRI mice--a suitable shock model for testing new PAF receptor antagonists. Correlation with eicosanoid related substances.

The effects of PAF antagonists, of substances which influence the arachidonic acid metabolism, and of dexamethasone and ketotifen were evaluated in an acute PAF-induced mortality model in female NMRI mice. We established a dependence of sensitivity to PAF on strain (AB mice showed no dose dependence) and on sex of the animals as well as on the PAF charges used in our experiments. PAF produced resistance in surviving animals against the PAF-induced death on repeated application.

Influence of aminophylline and ketotifen in comparison to the lipoxygenase inhibitors NDGA and esculetin and the PAF antagonists WEB 2170 [correction of 2107] and BN 52021 on endothelin-1 induced vaso- and bronchoconstriction.

Theophylline (p less than 0.05) and ketotifen (p greater than 0.05) markedly reduced, but the lipoxygenase inhibitors and PAF receptor antagonists were without any influence on the endothelin-1 (ET-1 1 nmol/kg i.

[Modification of lipoxygenase products in bone by the linoleic acid content of the diet].

Eicosanoids are supposed to participate in the regulation of bone metabolism. 30 male white rats of the wistar strain were fed on a diet rich in linoleic acid (LA), on a diet poor in LA and on a pellet diet after 3 month up to an age of 5 month. The formation of leukotrienes (LT) C4, D4, and E4 from the proximal tibia metaphysis after LA rich diet has been compared to the formation from LA poor and pellet diet.

Influence of iloprost and various prostaglandin derivatives on mouse skin allograft survival, HLA-DR antigen expression and eicosanoid metabolism by human leukocytes.

Treatment of mice bearing allogeneic tail skin grafts with iloprost, a stabilized prostacyclin derivative, as well as dexamethasone prolonged graft survival. Nalador and flunoprost, stabilized prostaglandin E analogues, had similar but weaker effects. The thromboxane agonist U 46619 had no effect on graft rejection.

Influence of inhibitors of the eicosanoid metabolism, of antagonists of the eicosanoids and of PAF on mortality assayed in three biochemically characterized shock models.

Experiments were carried out to lower the mortality (LD70-90) of rats in ovalbumin-induced anaphylactic (DA) shock and in endotoxin-induced (ET) shock, and of mice after injection of Platelet-activating Factor (PAF shock) comparing the effects of the cyclooxygenase (COX)-inhibitors aspirin (ASA), indomethacin, of the COX-/lipoxygenase (LOX)-inhibitors nordihydroguajaretic acid (NDGA), phenidone and X 86 (analogue of BW 755c), of the inhibitor of thromboxane (TX) synthesis HOE 944, of the TX-antagonist BM 13177, of the PAF-antagonist BN 52021 and of ketotifen. Ketotifen was strongly effective in DA shock, COX- and LOX-inhibitors only slightly. Combined COX- and LOX-inhibitors and BN 52021 showed good effects in the ET shock.

Inhibition of lipoxygenase (LOX) or of cyclooxygenase (COX) improves survival of rats in endotoxin shock.

In a well defined endotoxin (ET) shock model we compared the influence of a selective LOX-inhibitor FLM 5011 and the COX-inhibitor Acetylsalicylic acid (ASA) on survival as well as on their effects on TXB2 and 6-oxo-PGF1 and on selected parameters characterizing the shock syndrome. Pretreatment with both substances reduced the lethality rate. Neither TXB2 nor the PGF1 concentration revealed a consistent trend after therapeutic intervention.

Influence of the PG-analogues iloprost, nalador and nileprost on rejection time and TXB2 content of murine tail skin allografts.

Iloprost (2 X 330 micrograms/kg sc./d) better than nalador (2 X 500 micrograms/kg sc./d) prolonged the average time until the complete rejection of murine tail skin allografts in inbred mice.