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Thromb Haemost 1985; 54(04): 756-759
DOI: 10.1055/s-0038-1660126
Original Article
Schattauer GmbH Stuttgart

Evidence for a Direct Effect on Vascular Permeability of Platelet-Activating Factor Induced Hemoconcentration in the Guinea Pig

Dean A Handley
The Platelet Department, Preclinical Research, Sandoz Research Institute, East Hanover, N. J., USA
,
Mark L Lee
The Platelet Department, Preclinical Research, Sandoz Research Institute, East Hanover, N. J., USA
,
Robert N Saunders
The Platelet Department, Preclinical Research, Sandoz Research Institute, East Hanover, N. J., USA
› Author Affiliations
Further Information

Publication History

Received 24 May 1985

Accepted 13 August 1985

Publication Date:
19 July 2018 (online)

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Summary

The ability of synthetic platelet-activating factor (PAF) given intravenously to produce loss (extravasation) of protein rich plasma (resulting in hemoconcentration) has been examined using guinea pigs. Hemoconcentration induced by PAF was not prevented by prior administration of inhibitors of thromboxane synthetase (7-(3-pyridyl)heptanoic acid, UK-37,248-01), PGI2, aspirin, indomethacin or antiserum induced thrombocytopenia. Calcium channel blockers (nifedipine, verapamil, diethyl-amino octyltrimethoxybenzoate, diltiazem), antihistamines (pyrilamine, cimetidine, diphenhydramine), or the elevator of cAMP IBMX were ineffective in blocking PAF-induced hemoconcentration. In contrast, CV-3988, reported to be a specific antagonist to PAF, was 98% inhibitory of PAF extravasation when given i. a. at 3.5 mg/kg. The ED50 was 0.14 mg/kg I. A. and 15 mg/kg p.o. against 75 ng/kg PAF. These data suggest that PAF-induced hemoconcentration involves receptor mediated alterations of vascular permeability that are inhibited by a specific PAF antagonist.

Keywords

Platelet-activating factor - Guinea pig - Extravasation - Endothelial permeability - Thromboxane inhibitors - Calcium channel blockers - Antihistamines
 

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