Effects of endothelin-1 on bacterial clearance in rabbits

Abstract

As elevated endothelin-1 (ET-1) levels have been reported in systemic inflammatory diseases, the role of ET-1 as a promoter of inflammatory reactions is currently under investigation. The purpose of this study was to investigate the potential influence of ET-1 on systemic vascular pressure and immune function in terms of blood clearance and organ distribution of injected Escherichia coli in a rabbit model. To enable quantification of the clearance process, defined numbers of exogenous E. coli (10⁸ cfu) were injected intravenously 60 min after starting the infusion of ET-1 (0.2 μg kg⁻¹ min⁻¹; n=9) or after saline infusion (controls, n=9). Parameters monitored were arterial blood pressure, airway pressure, serum lactate concentrations and rates of bacterial elimination from the blood. At 180 min after E. coli injection, the animals were killed, and tissue samples of liver, kidney, spleen and lung were collected for bacterial counts. ET-1 infusion produced an increase in mean arterial pressure (83.9±3.9 mmHg vs. 50.1±4.1 mmHg at 120 min; P< 0.01) associated with higher serum lactate concentrations (12.6±1.3 vs. 5.4±0.3 mg dL⁻¹; P< 0.001) and a delayed bacterial elimination from the blood compared with controls. Furthermore, there was increased colonization of the lungs (3.6±0.5×10³ cfu vs. 745±120 cfu; P<0.01), spleen (142.4±45.4×10³ cfu vs. 22.7±5.2×10³ cfu; P<0.05) and kidney (758±329 vs. 357±151 cfu; NS), reflecting a reduced bacterial killing function.