EVIDENCE FOR INDUCIBLE NITRIC-OXIDE SYNTHASE IN SPONTANEOUSLY HYPERTENSIVE RATS

This study investigates the mechanism of the production of nitric oxid e (NO) caused by lipopolysaccharide (LPS) in spontaneously hypertensiv e rats (SHR) or Wistar-Kyoto (WKY) rats. The injection of LPS (5 mg/ k g, i.v.) caused a mild hypotension in WKY rats, while it induced a mor e severe hypotensive effect in SHR. The basal level of plasma nitrite was slightly higher in SHR than in WKY rats. At 3 h after injection of LPS, the increment in plasma nitrite was more significant in SHR. Pri or to the treatment of rats with LPS, the plasma level of tumor necros is factor-alpha (TNF alpha) was also higher in SHR than in WKY rats, a nd LPS induced a more significant increase of TNF alpha level (at 1 h) in SHR. In rats treated with LPS, acetylcholine-induced relaxation wa s significantly impaired in thoracic aortic rings obtained from WKY ra ts, but not in those from SHR. By contrast, L-arginine (1 mM) did not cause any relaxations in rings without the endothelium obtained from W KY rats while it slightly relaxed those from SHR, and this difference was further augmented by treatment of rats with LPS for 3 h. In additi on, the basal cGMP level was higher in SHR, which was inhibited by ami noguanidine (AG, 1 mM). The treatment of rats with LPS further increas ed the formation of cGMP in both strains and this increment was greate r in SHR than in WKY rats, which was also attenuated by AG to a simila r level between both strains. Interestingly, an expression of inducibl e NO synthase (NOS II) protein was only observed in SHR, and further e nhanced by treated rats with LPS. We conclude that an increased produc tion of NO in SHR, which was further enhanced by LPS, is attributed to a basal expression of NOS II. (C) 1996 Academic Press, Inc.