General Physiology and Biophysics Revised manuscript #1 Title: Consequences of lipopolysaccharide and omega-3 fatty acids administration on aortic function of spontaneously hypertensive rats Running title: Effect of lipopolysaccharide in SHR rats

Abstract The aim of the work was to study the dealyed effect of lipopolysaccharide (LPS) administration on endothelial function of the aorta of rats with genetic hypertension (SHR). Further, the possibility to ameliorate LPS-induced changes by omega-3 fatty acids (PUFA) was tested. Rats received bolus of 1mg/kg LPS i.p.; PUFA were administered in the dose of 30 mg/kg daily for 10 days p.o.. Ten days after LPS, the body weight gain of LPS rats was statistically lower compared to controls. PUFA administration to LPS rats had no effect on this paramater. The TBARS and NAGA concentrations in plasma were significantly increased in the LPS group and PUFA administration returned them to control values. In functional studies, phenylephrine (PE, 1 μmol/l) evoked contraction of aortas which was not statistically different among experimental groups. However, endothelium-dependent relaxation was depressed in the LPS group and PUFA slightly recovered it to control values. In conclusion, oxidative stress seems to be responsible for aortic endothelial dysfunction detected 10 days after administration of LPS to rats. PUFA slightly improved the function of the endothelium, probably thanks to their antioxidant properties. Prolonged administration of higher doses of PUFA should defend the vascular endothelium against detrimental effect of bacterial inflammation.