ROLE OF NITRIC-OXIDE IN LIPOPOLYSACCHARIDE-INDUCED MORTALITY FROM SPONTANEOUSLY HYPERTENSIVE RATS

To investigate whether nitric oxide (NO) contributed to a higher morta lity induced by lipopolysaccharide (LPS) in spontaneously hypertensive rats (SHR), NO synthase inhibitors were used to examine the mortality from LPS in SHR and normotensive Wistar-Kyoto (WKY) rats. We evaluate d the mortality from LPS in a series of doses (5, 10, or 20 mg/kg, i.v .) in the anesthetized rat. Plasma nitrite was measured before and at 1, 2, and 3 h after treated rats with LPS (5 mg/kg, i.v.). Pressure re sponses to N omega-nitro-L-arginine methyl ester (L-NAME) and aminogua nidine (AG) were performed in rats treated with or without LPS for 3 h . Thoracic aortic cyclic guanosine 3',5'-monophosphate (cGMP) levels w ere also assessed. Our results demonstrated that injection of LPS caus ed a dose-dependent mortality in both strains, having a more marked ef fect in SHR. The survival time of rats after injection of LPS (5 mg/kg , i.v.) was much shorter in SHR. A higher basal level of plasma nitrit e was observed in SHR and this difference was further augmented by LPS . The administration of L-NAME (3 mg/kg, i.v.) and AG (15 mg/kg, i.v.) 3 h after LPS had no significant effects on the survival time of WKY rats, but significantly prolonged that of SHR to a similar time of WKY rats. The injecton of L-NAME prior to LPS increased blood pressure of WKY rats by 28+/-5 mmHg and increased that of SHR by 38+/-4 mmHg. At 3 h after LPS, L-NAME had a greater presser effect in SHR than in WKY rats. By contrast, before rats injected with LPS, AG slightly increase d blood pressure of SHR by 7+/-3 mmHg but not of WKY rats (3+/-2 mmHg) , whereas it also had a greater presser effect in SHR than in WKY rats after treated rats with LPS far 3 h. In addition, LPS induced a highe r level of cGMP in SHR than in WKY rats, which was attenuated by in vi tro treatment of aortic rings from LPS-rats with L-NAME or AG to a sim ilar level in SHR and WKY rats. These results suggest that a higher le vel of NO evoked by LPS is associated with a higher mortality in SHR a nd we propose that the elevated NO synthesis in SHR may play an import ant role in the compensatory mechanisms activated to combat the hypert ensive state.