Regulation of vascular reactivity by E. coli endotoxin in vitro

Abstract

The regulatory role of Escherichia coli endotoxin on the reactivity of goat thoracic aorta to different vasoactive agents was examined in vitro. Helical strips of the aorta exhibited slow, sustained and dose-dependent contractile responses to exogenous norepinephrine (NE, 10 −7 to 10 −4 M), high potassium (80 mM) and high calcium (0.1–300 mM). Endotoxin exposure did not elicit any intrinsic effect on the aortic strips, which were otherwise quiescent. However, incubation of the tissue with different concentrations of endotoxin (1, 3 or 10 μg/ml) inhibited the NE-induced contractions in a dose-dependent manner, as was also evidenced by the increasing effective concentration-50 (EC 50) values for NE. The contractile responses to hypertonic K + and Ca 2+ were also significantly inhibited in tissue incubated with endotoxin. This effect was independent of the concentration of endotoxin in the bathing fluid. The contractile responses of aortic strips to NE, K + and Ca 2+ were restored to normal values by removing the endotoxin after several washes with Krebs–Henseliet (K–H) solution. The effect of acetylcholine (ACh, 10 −5 M) on the maintained tonic contracture of NE (10 −5 M) was assessed to investigate the role of nitric oxide (NO). The study suggests that the vascular hypo-reactivity induced by E. coli endotoxin may be partially due to α-adrenoceptor blocking action and to decreased uptake of Ca 2+ by microsomes and mitochondria in the presence of endotoxin. This regulatory effect of endotoxin was only transient in nature and did not permanently impair the contractility of vascular smooth muscles (VSMs). The involvement of nitric oxide was precluded since ACh failed to relax the NE-precontracted tissues with intact endothelium.