Hypotensive activity of PAF-acether in rats

Caillard, C; Mondot, S.; Zundel, J.L.; Julou, L

doi:10.1007/bf01965093

Cited by 39 publications

(17 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These findings have been confirmed recently by Seale et al (1991). Intravenous injection of PAF induced systemic hypotension in vivo (Caillard et al, 1982), pulmonary hypertension (Heffner et al, 1983), and increased protein extravasation in airways perfused by the systemic circulation, whereas oedema and protein permeability were not affected by PAF in lung parenchyma perfused by the pulmonary circulation (O'Donnell & Barnett, 1987;Sirois et al, 1988;1990;Chen et al, 1990). Inarrea et al (1984) reported that rat platelets did not bear PAF receptors and Pirotzky et al (1984) and Humphrey et al (1984) showed that intradermal injection of PAF in rat induced a plasma exudation which was independent of platelet and neutrophil contribution.…”

Section: Introductionsupporting

confidence: 65%

Effect of PAF on rat lung vascular permeability: role of platelets and polymorphonuclear leucocytes

Sirois

Lima

Fernandes

et al. 1994

British J Pharmacology

View full text Add to dashboard Cite

1 The objectives of the present experiments were to assess the contribution of polymorphonuclear leucocytes (PMNLs), platelets and their products such as thromboxane A2 (TxA2), histamine and 5-hydroxytryptamine to platelet activating factor (PAF)-mediated protein extravasation in rat lungs. 2 Intravenous injection of PAF (1.0 and 5.0 gg kg-') increased dose-dependently (up to 7.5 fold) the vascular permeability of the trachea, upper and lower bronchi to Evans blue dye (EB), a marker of albumin extravasation. The permeability of the pulmonary parenchyma was not affected significantly by PAF. 3 Thrombocytopenia induced by administration of the IgG fraction of goat anti-rat platelet serum (APS; 15 mg 100 g-', i.p., 16-18 h) reduced by 55, 58 and 40% the effects of the lower dose of PAF (1.0 jig kg-') and by 31, 23 and 15% the effects of the higher dose of PAF (5.0 gg kg-') on the permeability of the trachea, upper and lower bronchi respectively to albumin. 4 PMNL depletion induced by administration of rabbit anti-rat polymorphonuclear serum (ANS; 2 mg kg-', i.v., 24 h) did not reduce significantly the effects of the lower dose of PAF (1.0 fig kg-') on the airways, however the effects of the higher dose of PAF (5.0 ig kg-') on the permeability of the trachea, upper and lower bronchi to albumin were reduced by 43, 25 and 23% respectively. 5 The injection of both the anti-platelet and the anti-PMNL sera reduced by 61, 62 and 96% the effects of the lower dose of PAF (1.0 gg kg-') and by 44, 39 and 47% the effects of the higher dose of PAF (5.0 gig kg-') on the permeability of the trachea, upper and lower bronchi respectively. 6 The combined injection of the TxA2-mimetic (U-44069; 5.0 gig kg-') and PAF (1.0 and 5.0 gig kg-') in thrombocytopenic rats overcame the vascular permeability decrease induced by APS treatment. 7 Pretreatment of the animals with a combination of antagonists to histamine (mepyramine; 3.0 mg kg-') and 5-hydroxytryptamine (methysergide; 2.5 mg kg-') did not cause a significant inhibition of the effect of PAF (1.0 and 5.0 gig kg-') on EB extravasation in the airways. 8 These data show that the effect of intravenous PAF on rat vascular permeability is partly modulated by polymorphonuclear leucocyte and platelet activation. Our results suggest that following its release, TxA2 could increase postcapillary hydrostatic pressure by inducing a venoconstriction and potentiate the extravasation elicited by PAF. These results do not suggest a major role for histamine and/or 5-hydroxytryptamine on PAF-induced albumin extravasation.

show abstract

Section: Introductionsupporting

confidence: 65%

Effect of PAF on rat lung vascular permeability: role of platelets and polymorphonuclear leucocytes

Sirois

Lima

Fernandes

et al. 1994

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Therefore, PAF may be involved in a variety of immunopathological reactions triggered by different cellular effectors. In addition to its role in acute inflammatory reactions, PAF may be a mediator of shock when it is released intravascularly in massive amounts within a short period of time (23)(24)(25)(26)(27)37) . The present study shows that, after stimulation with TNF, rat peritoneal macrophages, human endothelial cells, and rat PMN synthesize and release PAF.…”

Section: Discussionmentioning

confidence: 99%

“…It was recently suggested that PAF is a mediator of endotoxic shock (22)(23)(24) on the basis of the following observations : (a) PAF is produced during endotoxic shock and experimental sepsis by Gram-negative bacteria (23)(24)(25) ; (b) infusion of experimental animals with PAF results in hypotension, decrease in cardiac output, and hypovolemic shock (26)(27)(28) ; (c) three PAF receptor antagonists (CV3988, kadsurenone, and SRI 63072) inhibit or reverse endotoxin-induced hypotension and, in this way, prolong the survival of rats (22,23,29) .…”

mentioning

confidence: 99%

Tumor necrosis factor/cachectin stimulates peritoneal macrophages, polymorphonuclear neutrophils, and vascular endothelial cells to synthesize and release platelet-activating factor.

Camussi

Bussolino

Salvidio

et al. 1987

The Journal of Experimental Medicine

340

133

View full text Add to dashboard Cite

Platelet-activating factor (PAF)' is a mediator of inflammation with a wide range of biological activities (see reference 1 for review) . PAF was initially recognized as a product of IgE-sensitized rabbit basophils (2) and was identified with 1-0-alkyl-2-sn-glyceryl-3-phosphorylcholine (3-5). It was subsequently shown that PAF is synthesized after appropriate stimulation by monocytes/macrophages (6-9), polymorphonuclear neutrophils (7, 10, 11), platelets (12) and endothelial cells (13-15) . PAF induces aggregation and degranulation of platelets (2, 16), stimulates contraction of smooth muscle (17), promotes chemotaxis and granule secretion of neutrophils (18-19) and monocytes (20), increases vascular permeability, and alters the vascular tone (21).It was recently suggested that PAF is a mediator of endotoxic shock (22-24) on the basis of the following observations : (a) PAF is produced during endotoxic shock and experimental sepsis by Gram-negative bacteria (23-25) ; (b) infusion of experimental animals with PAF results in hypotension, decrease in cardiac output, and hypovolemic shock (26-28) ; (c) three PAF receptor antagonists (CV3988, kadsurenone, and SRI 63072) inhibit or reverse endotoxin-induced hypotension and, in this way, prolong the survival of rats (22,23,29) .Tumor necrosis factor/cachectin (TNF) is a mediator of endotoxic shock (30). Because TNF administration to experimental animals reproduces several aspects of PAF infusion (30), it seems possible that PAF is synthesized in response to

show abstract

“…Receivedfor publication 9 June 1986 and in revisedform 13 January 1987. Recently, platelet-activating factor (PAF,'I -0-alkyl-2-acetylsn-glycerophosphorylcholine), a potent ether lipid, has been suggested as an important mediator in endotoxic shock (9-1 1). This suggestion is based on the following evidence: (a) infusion of exogenous PAF into whole animals caused systemic hypotension, decreased cardiac output (12,13), and increased pulmonary vascular permeability (14)(15)(16); (b) PAF is produced during experimental gram-negative sepsis and endotoxic shock (10, 1 1); (c) two structurally different PAF antagonists, CV 3988 and kadsurenone, have been reported to inhibit endotoxin-induced hypotension and prolong survival in rats (9,10).…”

Section: Introductionmentioning

confidence: 99%

Platelet-activating factor mediates hemodynamic changes and lung injury in endotoxin-treated rats.

Chang¹,

Feddersen²,

Henson³

et al. 1987

J. Clin. Invest.

345

119

View full text Add to dashboard Cite

Within 20 min after intraperitoneal injection of Salmonella enteritidis endotoxin in rats, blood platelet-activating factor (PAF) increased from 4.3±1.3 to 13.7±2.0 ng/ml (P < 0.01) and lung PAF from 32.3±4.9 to 312.3±19.6 ng (P < 0.01), but not lung lavage PAF. We tested the effect of PAF receptor antagonists, CV 3988 and SRI 63-441, on endotoxin-induced hemodynamic changes and lung vascular injury. Pretreatment with CV 3988 attenuated systemic hypotension, preserved hypoxic pulmonary vasoconstriction, and prolonged survival of awake catheter-implanted endotoxin-treated (20 mg/kg) rats. Pretreatment with SRI 63-441 prevented the depressed hypoxic pulmonary vasoconstriction after low dose (2 mg/kg) endotoxin. Both CV 3988 and SRI 63441 blocked the increased extravascular accumulation of 125I-albumin and water in perfused lungs isolated from endotoxin-treated rats. We conclude that PAF is produced in the lung during endotoxemia and may be an important mediator of the systemic and pulmonary hemodynamic changes as well as the acute lung vascular injury after endotoxemia.

show abstract

Hypotensive activity of PAF-acether in rats

Cited by 39 publications

References 14 publications

Effect of PAF on rat lung vascular permeability: role of platelets and polymorphonuclear leucocytes

Effect of PAF on rat lung vascular permeability: role of platelets and polymorphonuclear leucocytes

Tumor necrosis factor/cachectin stimulates peritoneal macrophages, polymorphonuclear neutrophils, and vascular endothelial cells to synthesize and release platelet-activating factor.

Platelet-activating factor mediates hemodynamic changes and lung injury in endotoxin-treated rats.

Contact Info

Product

Resources

About