Higher level of plasma nitric oxide in spontaneously hypertensive rats

We had detected a slightly, but significantly, higher level of plasma nitri te/nitrate in the sponstanously hypertensive rat (SHR) by using the nitric oxide (NO) analyzer (Sievers 280 NOA), which converts nitrate (including ni trate converted from nitrite) to NO. Here, we examined whether the release of NO from protein-bound dinitrosyl nonheme iron complexes (DNIC) contribut es to the elevated plasma nitrate level in the SHR. The SHR and their genet ic normotensive controls, Wistar-Kyoto rats (WKY), were anesthestized and c annulized for monitoring blood pressure, collecting a blood sample, and the administration of endotoxin (lipopolysaccharide [LPS]). The nitrate levels tan indicator of NO formation) in the plasma and the aorta were measured b y an NO analyzer. In addition, the relaxation of acetylcholine (ACh) in the presence or absence of N-omega-nitro-L-arginine methyl ester (L-NAME) was also examined in thoracic aortae obtained from both strains. The slight, bu t significant, increase of basal nitrate levels in the plasma and aorta wer e observed, and the former was further enhanced in SHR treated with LPS for 3 h. In vitro, the ACh-induced relaxation was attenuated in the aortae obt ained from SHR. However, this difference between SHR and WKY (without LPS t reatment) was abolished by treatment of rings with L-NAME (30 mu mol/L), su ggesting that an impairment of NO formation was observed in the SHR. After rats were treated with LPS for 3 h, the ACh-induced relaxation was reduced in the WKY, but not in the SHR. In addition, a 10-fold increase of L-NAME w as needed to abolish the difference in AChinduced relaxation between SHR an d WKY, indicating an expression of inducible NO synthase in both strains tr eated with LPS. We suggest that the elevated plasma NO level in SHR may be due to the release of NO from DNIC in the vascular bed to combat the hypert ensive state. (C) 1999 American Journal of Hypertension, Ltd.