Abstract
To investigate whether nitric oxide (NO) contributed to a higher mortality 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 evaluated 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 responses to N(ω)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG) were performed in rats treated with or without LPS for 3 h. Thoracic aortic cyclic guanosine 3',5'-monophosphate (cGMP) levels were also assessed. Our results demonstrated that injection of LPS caused a dose-dependent mortality in both strains, having a more marked effect 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 nitrite 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 injection 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 pressor effect in SHR than in WKY rats. By contrast, before rats injected with LPS, AG slightly increased blood pressure of SHR by 7 ± 3 mmHg but not of WKY rats (3 ± 2 mmHg), whereas it also had a greater pressor effect in SHR than in WKY rats after treated rats with LPS for 3 h. In addition, LPS induced a higher level of cGMP in SHR than in WKY rats, which was attenuated by in vitro treatment of aortic rings from LPS-rats with L-NAME or AG to a similar level in SHR and WKY rats. These results suggest that a higher level of NO evoked by LPS is associated with a higher mortality in SHR and we propose that the elevated NO synthesis in SHR may play an important role in the compensatory mechanisms activated to combat the hypertensive state.
Original language | English |
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Pages (from-to) | 1223-1230 |
Number of pages | 8 |
Journal | Life Sciences |
Volume | 60 |
Issue number | 15 |
DOIs | |
Publication status | Published - Mar 7 1997 |
Keywords
- Wistar-Kyoto rats
- lipopolysaccharide
- nitric oxide synthase inhibitors
- spontaneously hypertensive rats
ASJC Scopus subject areas
- General Pharmacology, Toxicology and Pharmaceutics
- General Biochemistry,Genetics and Molecular Biology