Exaggerated Hypotension by N-formylmethionylleucyl-phenylalanine in Indomethacin Pretreated Rats. Role of Toxic Oxygen

Overview

Journal Agents Actions

Specialty Pharmacology

Date 1986 Mar 1

PMID 3706053

Citations 1

Authors

U B Olsen

V Bille-Hansen

Affiliations

Soon will be listed here.

Abstract

In pentobarbital anaesthetized rats the intravenous administration of the oligopeptide N-formyl-Met-Leu-Phe (FMLP) is shown to produce a short-lasting hypotension. When the animals have been pretreated with indomethacin, FMLP induces a marked and sustained blood pressure fall. This exaggerated hypotensive response to FMLP is absent in rats which have received a low dose of endotoxin at the day before, and is greatly reduced in animals treated with ascorbic acid or dimethylsulfoxide. In addition, the duration of hypotension is shortened in rats which have been partially depleted of leukocytes by daily methotrexate dosages, or which simultaneously receive drug treatments known to enhance vessel wall cyclic AMP levels like isoprenaline, glucagon or theophylline. The results suggest that after the FMLP administration toxic oxygen species generated by leukocytes contribute to the development of the cardiovascular dysfunction. Endothelial cAMP is suggested to control the sensitivity of the cardiovascular system to these reactive species.

Citing Articles

Endotoxin pretreatment enhances neutrophil FMLP-receptor binding and activity in guinea pigs.

Olsen U, Bille-Hansen V Agents Actions. 1987; 21(1-2):177-83.

PMID: 3115069 DOI: 10.1007/BF01974939.

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