PAF-acether and endotoxin display similar effects on rat mesenteric microvessels: inhibition by specific antagonists

V Lagente, ZB Fortes, J Garcia-Leme and BB Vargaftig

Departamento de Farmacologia, Universidade de Sao Paulo, Brazil.

The activity of platelet activating factor (PAF-acether) and the effects of specific antagonists BN 52021 and WEB 2086 on microvessels were studied. The mesentery of anaesthetized male Wistar rats was exteriorized and arranged for microscopic observation of the microcirculation in situ. Vessel diameters were measured with an image splitting micrometer adjusted to the phototube of the microscope. Images were displayed on the monitor screen of a closed-circuit television system. Topical application of PAF (10, 100 and 200 microM) enlarged the diameter of mesenteric arterioles and venules, which was antagonized by PAF antagonists administered i.v. (1 mg/kg) or topically (10 microM). Bolus injection (1 micrograms/kg) or perfusion (100 ng/kg/min) of PAF significantly decreased mean arterial blood pressure of the animals and slightly increased arteriolar diameters. These effects were blocked by the PAF antagonists. Endotoxin (10-20 mg/kg i.v.) significantly enlarged arteriolar diameters and produced a significant drop of arterial blood pressure. These effects were blocked by the PAF antagonists at doses equivalent to those used to antagonize the effects of PAF. The leukocyte activator fMLP, as well as lyso-PAF and PAF antagonists, were devoid of effects on the microcirculation when applied topically or injected i.v. We conclude that mesenteric microvessels contribute to the hypotensive effect of PAF and endotoxin and that PAF is released at the mesenteric area during endotoxic shock.

Volume 247, Issue 1, pp. 254-261, 10/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics