Modulation of Nitric Oxide Synthase Activity in Brain, Liver, and Blood Vessels of Spontaneously Hypertensive Rats by Ascorbic Acid: Protection from Free Radical Injury

• Published in: Clinical and experimental hypertension (1993) Vol. 27; no. 6; pp. 497 - 508
• Main Authors: Newaz, M. A., Yousefipour, Z., Nawal, N. N. A.
• Format: Journal Article
• Language: English
• Published: Colchester Informa UK Ltd 01.08.2005; Taylor & Francis
• Subjects: Animals; antioxidant; Arterial hypertension. Arterial hypotension; Ascorbic Acid - pharmacology; Biological and medical sciences; Blood and lymphatic vessels; Blood Vessels - drug effects; Blood Vessels - enzymology; Brain - drug effects; Brain - enzymology; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Experimental diseases; free radical; Free Radical Scavengers - pharmacology; Hypertension - metabolism; Hypertension - physiopathology; lipid peroxide; Liver - drug effects; Liver - enzymology; Male; Medical sciences; nitric oxide synthase; Nitric Oxide Synthase - metabolism; Oxidative Stress - physiology; Rats; SHR; Hypertension; Ascorbic acid; Rat; Enzyme; Liver; Rodentia; Vitamin; Cardiovascular disease; Antioxidant; Nitric-oxide synthase; Free radical; Encephalon; Vertebrata; Mammalia; Animal; Peroxides; Oxidoreductases; nitric oxide synthase; SHR; lipid peroxide
• ISSN: 1064-1963; 1525-6006
• DOI: 10.1081/CEH-200067681

End organ damage in essential hypertension has been linked to increased oxygen free radical generation, reduced antioxidant defense, and/or attenuation of nitric oxide synthase (NOS) activity. Ascorbic acid (AA), a water-soluble antioxidant, has been reported as a strong defense against free radicals in both aqueous and nonaqueous environment. In this study we examined the hypothesis that antioxidant ascorbic acid may confer protection from increased free radical activity in brain, liver, and blood vessels of spontaneously hypertensive rats (SHR). Male SHRs were divided into groups: SHR + AA (treated with AA, 1 mg/rat/day; for 12 weeks) or SHR (untreated). Wister-Kyoto rats (WKY) served as the control. Mean systolic blood pressure (SBP) in treated and untreated SHR was 145 ± 7 mmHg and 142 ± 8 mmHg, respectively. AA treatment prevented the increase in systolic blood pressure in SHR by 37 ± 1% (p < 0.05). NOS activity in the brain, liver, and blood vessels of WKY rat was 1.82 ± 0.02, 0.14 ± 0.003, and 1.54 ± 0.06 pmol citruline/mg protein, respectively. In SHR, total NOS activity was significantly reduced by 52 ± 1%, 21 ± 3%, and 44 ± 4%, respectively. AA increased NOS activity in brain, liver, and blood vessels of SHR from 0.87 ±.03, 0.11 ±.01, and 0.87 ±.08 pmol citruline/mg protein to 0.93 ± 0.01, 0.13 ± 0.001, and 1.11 ± 0.03 pmol citruline/mg protein (p < 0.05), respectively. Lipid peroxides in the brain, liver, and blood vessels from WKY rats were 0.87 ± 0.06, 0.11 ± 0.005, and 0.47 ± 0.04 nmol MDA equiv/mg protein, respectively. In SHR, lipid peroxides in brain, liver, and blood vessels were significantly increased by 40 ± 3%, 64 ± 3%, and 104 ± 13%, respectively. AA reduced lipid peroxidation in liver and blood vessels by 17 ± 1% and 34 ± 3% but not in brain. Plasma lipid peroxides were almost doubled in SHR (p < 0.01) together with a reduction in total antioxidant status (6 ± 0.1%; p < 0.05), nitrite (53 ± 2%; p < 0.05) and superoxide dismutase (SOD) activity (36 ± 2%; p < 0.05). AA treatment reduced plasma lipid peroxide (p < 0.001), and increased TAS (p < 0.001), nitrite (p < 0.001), and SOD activity (p < 0.001). From this study, we conclude that brain, liver, and blood vessels in SHR are susceptible to free radical injury, which reduces the availability of NO either by scavenging it or by reducing its production via inhibiting NOS. In addition, brain, liver, and blood vessels in SHR; may be protected by antioxidant, which improves total antioxidant status, and SOD thus may prevent high blood pressure and its complications.