Higher level of plasma nitric oxide in spontaneously hypertensive rats

• Published in: American journal of hypertension 1999-05, Vol.12 (5), p.476-482
• Main Authors: Wu, Chin-Chen, Yen, Mao-Hsiung
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Aorta, Thoracic - physiopathology; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Cardiology. Vascular system; Enzyme Inhibitors - pharmacology; Experimental diseases; Hypertension - blood; Hypertension - metabolism; Hypertension - pathology; Lipopolysaccharides - pharmacology; Male; Medical sciences; N ω-nitro- l-arginine methyl ester; NG-Nitroarginine Methyl Ester - pharmacology; Nitrates - metabolism; Nitric oxide; Nitric Oxide - metabolism; Nitrites - metabolism; Nω-nitro-L-arginine methyl ester; Rats; Rats, Inbred SHR; Rats, Inbred WKY; spontaneously hypertensive rats; Vasodilation - drug effects; Vasodilator Agents - pharmacology
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/S0895-7061(99)00008-4

We had detected a slightly, but significantly, higher level of plasma nitrite/nitrate in the sponstanously hypertensive rat (SHR) by using the nitric oxide (NO) analyzer (Sievers 280 NOA), which converts nitrate (including nitrate converted from nitrite) to NO. Here, we examined whether the release of NO from protein-bound dinitrosyl nonheme iron complexes (DNIC) contributes to the elevated plasma nitrate level in the SHR. The SHR and their genetic normotensive controls, Wistar-Kyoto rats (WKY), were anesthestized and cannulized for monitoring blood pressure, collecting a blood sample, and the administration of endotoxin (lipopolysaccharide [LPS]). The nitrate levels (an indicator of NO formation) in the plasma and the aorta were measured by an NO analyzer. In addition, the relaxation of acetylcholine (ACh) in the presence or absence of N ω-nitro- l-arginine methyl ester (L-NAME) was also examined in thoracic aortae obtained from both strains. The slight, but significant, increase of basal nitrate levels in the plasma and aorta were 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 obtained from SHR. However, this difference between SHR and WKY (without LPS treatment) was abolished by treatment of rings with L-NAME (30 μmol/L), suggesting 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 was needed to abolish the difference in ACh-induced relaxation between SHR and WKY, indicating an expression of inducible NO synthase in both strains treated 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 hypertensive state.