Background: Endotoxemia causes paradoxical effects on the systemic and pulmonary vasculature,
resulting in systemic hypotension and increased pulmonary artery pressure. The local
production of inflammatory mediators may have important effects on vascular tissue function.
The purpose of this study was to delineate differences in function and the expression
of tissue cytokine genes in the aorta and pulmonary artery after endotoxemia.
Methods: Thoracic aorta and pulmonary artery branches were isolated from adult Sprague-
Dawley rats (n = 4–6/group) 6 h after intraperitoneal injection of lipopolysaccharide (Salmonella
typhimurium, 20 mg/kg) or vehicle (1.0 mL of saline). Arteries were suspended in perfused
organ baths for measurement of isometric force transduction, and dose–response curves
to phenylephrine (0.01–10 micromol/L), acetylcholine (0.01–10 micromol/L), and sodium nitroprusside
(0.001–10 micromol/L) were generated. The vascular segments were also assessed
for expression of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) by semiquantitative reverse transcriptase–
polymerase chain reaction.
Results: Endotoxemia resulted in decreased contractility of the aorta (508.63 ± 81.89 mg vs. 2544.16 ± 142.05 mg in the vehicle group) and pulmonary artery (352.50 ± 38.11 mg vs. 535.83 ±
45.51 mg in the vehicle group) and decreased endothelium-dependent pulmonary artery relaxation
(52.86 ± 5.63% vs. 80.58 ± 6.39% in the vehicle group). Expression of IL-1β and iNOS
mRNA by the pulmonary artery, but not the aorta, increased significantly in the endotoxintreated
animals. Interleukin-6 was increased in both the pulmonary artery and the aorta during
endotoxemia, whereas TNF concentrations were unchanged.
Conclusions: Endotoxemia may cause aortic hypocontractility and impaired endothelium-dependent pulmonary artery vasorelaxation. Expression of inflammatory genes in vascular tissue
may be site-specific and may contribute to the functional derangements associated with sepsis.
