Influence of E. coli Endotoxin on Serotonin Contractions of the Rabbit Aortic Strip. ∗

Abstract

The mechanisms by which bacterial endo-toxins disrupt peripheral vascular function remain largely conjectural (1). Among the explanations advanced for the shock-like collapse of the individual following endotoxin are a release of mediators such as his-tamine, serotonin, catecholamin.es, etc. (1), a direct biphasic action on vascular smooth muscle(2), an increased responsiveness to catecholamines(3), and a depressing action on myocardial muscle(2). Data based on in vitro experiments to support a direct action of bacterial endotoxins on smooth muscle are for the most part inconclusive (1). The present report describes experiments with isolated strips of aortic smooth muscle which show that bacterial endotoxin under in vitro conditions potentiates the contractile response of smooth muscle to serotonin (5HT).

Materials and methods. Batches of E. coli endotoxin obtained commercially (Difco) were tested for biological activity by their ability to elicit a modified Shwartzman reaction in the abdominal skin of rabbits when a combination of (50 μg) epinephrine and (50 μg) endotoxin was injected intrader-mally(4). The material used produced positive skin lesions in all of the 6 rabbits so treated.

Helical strips of rabbit thoracic aorta (3-4 mm wide and 35-40 mm long) were prepared, suspended in a 20 ml organ bath containing Krebs-bicarbonate Ringer solution maintained at 37°C, through which a gas mixture of 5% CO₂ and 95% O₂ was bubbled continuously, and reactivity was determined as described previously (5). Complete dose-response curves were established in each case for serotonin, epinephrine and norepi-nephrine. A concentration of serotonin, epinephrine and norepinephrine was then selected which produced approximately 50-60% of the maximal contractile response and this was used as the standard test dose for poten-tiation studies with endotoxin. The E. coli preparation was added to the bath solution and routinely left in contact with the aortic strip for 10 minutes prior to addition of a test dose of serotonin.