The effect of 1-O-alkyl-2-acetyl-Sn-glycero- 3-phosphocholine (paf-acether) on the arterial wall

Bourgain, R.H.; Maes, L.; Braquet, P.; Andries, R.; Touqui, Lhousseine; Braquet, M.

doi:10.1016/0090-6980(85)90184-4

Cited by 85 publications

(27 citation statements)

References 16 publications

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“…In experiments following the time-course of the response beyond the usual 10 min observation period, cessation of antagonist infusion resulted in a rapid increase in coronary perfusion pressure which could be readily reversed by further antagonist infusion. This remarkable cycle of events has been paralleled in experiments on the thrombotic action of Paf in superfused mesenteric bed in situ in which Paf has a protracted action which may be reversed by BN 52021 up to 3 h after superfusion of Paf (Bourgain et al, 1985). These authors suggested that the long-lasting effect of Paf may be due to autogeneration.…”

Section: Discussionmentioning

confidence: 77%

Antagonism of vasoconstriction induced by platelet‐activating factor in guinea‐pig perfused hearts by selective platelet‐activating factor receptor antagonists

Piper

Stewart

1987

British J Pharmacology

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1 Platelet-activating factor (Paf) is a potent coronary vasoconstrictor in rat, guinea-pig, dog and pig.The present study investigated the mechanism and duration of action of Paf in guinea-pig isolated, Krebs-perfused hearts. 2 Dose-related and sustained decreases in cardiac contractility and increases in coronary perfusion pressure were elicited by bolus doses of Paf (0.3-100 pmol). 3 Platelet-activating factor (30 pmol) induced increases in the production of immunoreactive thromboxane B2 (TXB2), leukotriene B4 (LTB4) and LTC4, but not 6-keto-prostaglandin F,. (6-keto-PGF,.). In addition, the release of leukotriene-like material following Paf was observed using on-line superfusion bioassay. 4 The coronary vasoconstrictor actions of Pafwere partially antagonized by the leukotriene receptor antagonist, FPL 55712 (1.9 giM), or by indomethacin (2.8 juM). The combined use of these compounds did not result in further significant inhibition. 5The Paf receptor antagonists, BN 52021 (30yM) and L 652, 731 (1O pM), antagonized both the increase in coronary perfusion pressure and the decrease in cardiac contractility induced by Paf (10-100 pmol) in a sunnountable and relatively selective manner. 6 The effects.of a bolus dose of 100 pmol Paf were sustained in excess of 18 min. Exogenous Paf underwent little metabolism on passing through the coronary circulation with only 2% being converted to lyso-Paf and approximately 4% being retained by the heart after 18 min of perfusion. 7 These results suggest that the coronary vasoconstrictor actions of Paf are partially dependent on the release of vasoactive arachidonic acid metabolites. The extraordinary potency and the long-lasting action of Paf indicate a potential role for this pro-inflammatory mediator in disorders of the coronary circulation.

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Section: Discussionmentioning

confidence: 77%

Antagonism of vasoconstriction induced by platelet‐activating factor in guinea‐pig perfused hearts by selective platelet‐activating factor receptor antagonists

Piper

Stewart

1987

British J Pharmacology

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“…Leukotrienes C4 and D4 have been shown to increase vascular permeability (Dahlen et al, 1981), so it is possible that they could mediate Pafinduced effects on vascular permeability. A further possibility is that Pafinfusion leads to endogenous Paf release, as has been shown previously (Bourgain et al, 1985), and that the beneficial effects of BW755C or the corticosteroids can be attributed to an inhibition of this release. Paf biosynthesis is dependent on the significant haemoconcentration, probably as a consequence of increased vascular permeability.…”

Section: Discussionmentioning

confidence: 71%

Effects of inhibitors of arachidonic acid metabolism on Paf‐induced gastric mucosal necrosis and haemoconcentration

Wallace

Whittle

1986

British J Pharmacology

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The effects of several inhibitors of arachidonic acid metabolism on gastric necrosis, hypotension, haemoconcentration, leukopenia and plasma exudation induced by platelet‐activating factor (Paf) were studied in the rat. A 10 min intravenous infusion of Paf (100 ng kg−1 min−1) caused extensive gastric damage and a marked fall in systemic blood pressure which had not recovered to basal levels 30 min after the infusion had been terminated. Paf also caused significant haemoconcentration, plasma exudation and transient leukopenia. Pretreatment with dexamethasone (0.2 or 2 mg kg−1 s.c.) or prednisolone (20 mg kg−1 s.c.) two hours before Paf significantly reduced the gastric damage and accelerated the recovery of blood pressure after the Paf infusion. Likewise, BW755C (50 mg kg−1 p.o.) significantly reduced the gastric damage. Acute pretreatment with dexamethasone (2 mg kg−1 i.v.) 15 min before Paf, or with indomethacin (5 mg kg−1 s.c.), acetylsalicylic acid (10 mg kg−1 i.v.) or 1‐benzylimidazole (50 mg kg−1 s.c.) did not significantly affect the gastric damage induced by Paf. The Paf‐induced haemoconcentration and plasma exudation were significantly reduced by pretreatment with prednisolone (20 mg kg−1 s.c.) or BW755C (50 mg kg−1 p.o.), while Paf‐induced leukopenia was unaffected by either drug. These studies indicate that cyclo‐oxygenase products of arachidonic acid are unlikely to contribute significantly to the gastric damage or the prolonged hypotension induced by Paf. The ability of corticosteroids and BW755C to reduce the gastric damage, haemoconcentration and plasma exudation suggests that lipoxygenase products of arachidonic acid may contribute to these actions of Paf.

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“…28 A direct vasodilator effect on coronary arterial vessels has been demonstrated at PAF concentrations several orders of magnitude higher than those achieved in the present study. 23,27 Although statistically significant, the magnitude of PAF-induced collateral vasodilation during thromboxane A 2 receptor blockade was small.…”

mentioning

confidence: 96%

“…The modest increase in collateral flow could have resulted from vasodilators released by aggregating platelets including ADP, 11 histamine, 26 and prostacyclin or other prostanoids. 27 PAF-induced endothelium-dependent vasodilation could also have contributed to the vasodilation from PAF during SQ30,741 infusion. 28 A direct vasodilator effect on coronary arterial vessels has been demonstrated at PAF concentrations several orders of magnitude higher than those achieved in the present study.…”

mentioning

confidence: 99%

Effect of Platelet Activation on Coronary Collateral Blood Flow

Kinn

Bache

1998

Circulation

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Background-The platelet products thromboxane A 2 and serotonin have been shown to cause constriction of welldeveloped coronary collateral vessels. This study was performed to determine whether intravascular platelet activation produced with platelet activating factor (PAF) can cause a decrease in coronary collateral blood flow. Methods and Results-Collateral vessel growth was induced by embolization of a hollow stainless steel plug into the left anterior descending coronary artery (LAD) of adult dogs. The animals were returned to the laboratory 3 to 6 weeks later for surgical instrumentation and measurement of collateral blood flow. Collateral flow was assessed by measuring retrograde blood flow from the cannulated collateral-dependent artery. PAF (10 nmol) was injected into the left main coronary artery to allow products of platelet activation to reach collateral vessels arising from the left coronary system. PAF caused a vasoconstrictor response, which became maximal 3 minutes after injection and resulted in a 40.3Ϯ7.4% decrease in retrograde blood flow (32.1Ϯ2.1 to 19.6Ϯ3.2 mL/min; PϽ0.05). By 15 minutes after the PAF injection, both retrograde blood flow and transcollateral resistance had returned to normal. After pretreatment with the thromboxane A 2 receptor antagonist SQ30,741, the vasoconstrictor response to PAF was abolished and, in contrast to the decrease in retrograde blood flow from PAF alone, a weak vasodilator effect was unmasked. Conclusions-PAF caused a decrease in coronary collateral blood flow. This vasoconstrictor response required the participation of thromboxane A 2 .

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The effect of 1-O-alkyl-2-acetyl-Sn-glycero- 3-phosphocholine (paf-acether) on the arterial wall

Cited by 85 publications

References 16 publications

Antagonism of vasoconstriction induced by platelet‐activating factor in guinea‐pig perfused hearts by selective platelet‐activating factor receptor antagonists

Antagonism of vasoconstriction induced by platelet‐activating factor in guinea‐pig perfused hearts by selective platelet‐activating factor receptor antagonists

Effects of inhibitors of arachidonic acid metabolism on Paf‐induced gastric mucosal necrosis and haemoconcentration

Effect of Platelet Activation on Coronary Collateral Blood Flow

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