Triggering by Paf‐acether and adrenaline of cyclo‐oxygenase‐independent platelet aggregation

Abstract

Platelet‐activating factor (Paf‐acether, 1‐alkyl‐2‐acetyl‐sn‐glycero‐3‐phosphorylcholine) induced full aggregation and a limited release reaction of human platelets in plasma or in blood. Cyclo‐oxygenase inhibition with aspirin only reduced aggregation when induced by threshold amounts of Paf‐acether, whereas higher concentrations surmounted inhibition whether tested in citrated or in heparinized platelet‐rich plasma or blood. Aspirin‐induced inhibition of platelet secretion by Paf‐acether was insurmountable and independent of the anti‐coagulant used. Paf‐acether and adrenaline acted synergistically in inducing aggregation in citrate and in heparin. Aspirin in vitro or after oral ingestion at doses that suppressed aggregation induced by arachidonic acid alone, failed to reduce significantly the synergized aggregation induced by Paf‐acether alone or combined with adrenaline. Twenty‐four hours after the oral ingestion of aspirin, when aggregation by arachidonic acid remained blocked, a slight inhibitory activity on the effect of Paf‐acether noted 4 h after aspirin, had ceased. This was probably accounted for by the synthesis of thromboxane A2 by newly formed platelets, since the in vitro addition of aspirin, or of the thromboxane/endoperoxide receptor inhibitor 13‐azaprostanoic acid caused the 24 h platelets to behave in a manner similar to platelets collected 4 h after aspirin. The α2‐adrenoceptor inhibitor, yohimbine, blocked the direct effect of adrenaline as well as its synergism with Paf‐acether. Since the synergistic effect of Paf‐acether and adrenaline was maintained when thrombin‐degranulated platelets were used, and aspirin remained ineffective against it, it is clear that the augmented platelet responsiveness is not accounted for by the platelet release reaction. Paf‐acether and adrenaline act synergistically and stimulate platelets by cyclo‐oxygenase‐independent mechanisms, which may be relevant in human physiopathological conditions.

The effects of varying doses of aspirin on human platelet activation induced by PAF, collagen and arachidonic acid.

“…Aspirin has also been shown to partially inhibit ex vivo PAF-induced platelet aggregation and ATP release (Lecrubier et al, 1983;Rao et al, 1982) . Dose dependent inhibition at low but not high concentrations of PAF has also been reported (Cattaneo et al, 1985;Fouque & Vargaftig, 1984;Macconi et al, 1985). As a result, the effect of aspirin on PAF-induced platelet aggregation remains unclear.…”

“…In one study in which five healthy volunteers took 500 mg of aspirin daily for five days, there was no inhibition of PAF-induced aggregation . However, other investigators have shown aspirin inhibits aggregation induced by low concentrations of PAF but not at higher concentrations (Cattaneo et al, 1985;Fouque & Vargaftig, 1984;Macconi et al, 1985) and a recent study by McCulloch et al (1989) has suggested low dose aspirin can inhibit both platelet aggregation and release.…”

Correction of Endothelial Dysfunction in Diabetic Female Rats by Tetrahydrobiopterin and Chronic Insulin

“…These concentrations were selected based on a previous study [2]. After 15–30 s of topical application of the vasodilators, their effects were measured.…”

“…A 500-line television camera (JVC, Tokyo, Japan) was coupled to a trinocular microscope (Zeiss, Oberkochen, Germany) to facilitate observation of the enlarged image (×3,400) on the video screen. The shearing of the image enables the measurement of the vascular diameter [2]. …”

“…In male diabetic rats, several authors have demonstrated an impaired endothelium-dependent vasodilation in the aorta [1], in the mesenteric vascular bed [2, 3] and in the corpus cavernosum [4] as a consequence of endothelial dysfunction.…”