Platelet activating factor (PAF) involvement in endotoxin-induced hypotension in rats. Studies with PAF-receptor antagonist kadsurenone |
| |
Authors: | T W Doebber M S Wu J C Robbins B M Choy M N Chang T Y Shen |
| |
Institution: | Department of Membrane and Arthritis Research, Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065, USA |
| |
Abstract: | Evidence from three types of experiments indicates that platelet activating factor (PAF)1 is an important mediator of endotoxin-induced hypotension in rats. a) Endotoxin infusion stimulates the time-dependent appearance of PAF in the blood. b) PAF infusion results immediately (less than 30 sec) in hypotension while endotoxin-induced hypotension takes 3-5 min to occur, allowing time for PAF production. c) Infusion of the specific PAF-receptor antagonist kadsurenone (2.2 mumole/kg bolus, 0.9 mumoles/min/kg continuous infusion), which inhibits PAF-induced hypotension by 67%, causes a 67% reversal of endotoxin-elicited hypotension. An additional finding of this study is that rats respond hypotensively to each of a series of low-dose PAF infusions but only to the first low-dose endotoxin infusion. These endotoxin-refractory rats do respond to subsequent PAF infusions. |
| |
Keywords: | BSA bovine serum albumin DMSO dimethylsulfoxide i v intravenous MAP mean arterial pressure PAF platelet activating factor PBS phosphate buffered saline |
本文献已被 ScienceDirect 等数据库收录! |