Chronic administration of sodium nitrite prevents hypertension and protects arterial endothelial function by reducing oxidative stress in angiotensin II-infused mice

• Published in: Vascular pharmacology Vol. 102; pp. 11 - 20
• Main Authors: Ling, Wei Chih, Mustafa, Mohd Rais, Vanhoutte, Paul M, Murugan, Dharmani Devi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2018; Elsevier Science Ltd
• Subjects: Administration, Oral; Angiotensin; Angiotensin II; Animals; Antihypertensive Agents - administration & dosage; Antihypertensives; Antioxidants - administration & dosage; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Aorta, Thoracic - physiopathology; Arterial Pressure - drug effects; Arteries; Blood pressure; Blood vessels; Cardiovascular; Cyclic GMP; Cyclic GMP - metabolism; Diet; Disease Models, Animal; Drinking water; Endothelial function; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Fluorescence; Guanosine; Hypertension; Hypertension - chemically induced; Hypertension - metabolism; Hypertension - physiopathology; Hypertension - prevention & control; Male; Mice; Mice, Inbred C57BL; NADPH Oxidase 2 - metabolism; NADPH Oxidase 4 - metabolism; Nitric Oxide - metabolism; Nitrite; Nitrites; Nitrotyrosine; Oral administration; Oxidation resistance; Oxidative stress; Oxidative Stress - drug effects; Oxygen; Proteins; Reactive oxygen species; Renal artery; Renal Artery - drug effects; Renal Artery - metabolism; Renal Artery - physiopathology; Sodium; Sodium nitrite; Sodium Nitrite - administration & dosage; Tyrosine - analogs & derivatives; Tyrosine - metabolism; Vasodilation - drug effects; Western blotting; SBP; Systolic blood pressure; Hypertension; cyclic guanosine monophosphate; NADPH oxidase, NOX; RAS; cGMP; Nitrite; Endothelial function; EDR; NOS; spontaneously hypertensive rats; ROS; reactive oxygen species; endothelial nitric oxide synthase; nicotinamide adenine dinucleotide phosphate-oxidase; SHR; endothelium-dependent relaxation; renin-angiotensin system; Reactive oxygen species
• ISSN: 1537-1891; 1879-3649
• DOI: 10.1016/j.vph.2017.05.003

Abstract Aim Endothelial dysfunction accompanied by an increase in oxidative stress is a key event leading to hypertension. As dietary nitrite has been reported to exert antihypertensive effect, the present study investigated whether chronic oral administration of sodium nitrite improves vascular function in conduit and resistance arteries of hypertensive animals with elevated oxidative stress. Methods Sodium nitrite (50 mg/L) was given to angiotensin II-infused hypertensive C57BL/6J (eight to ten weeks old) mice for two weeks in the drinking water. Arterial systolic blood pressure was measured using the tail-cuff method. Vascular responsiveness of isolated aortae and renal arteries was studied in wire myographs. The level of nitrite in the plasma and the cyclic guanosine monophosphate (cGMP) content in the arterial wall were determined using commercially available kits. The production of reactive oxygen species (ROS) and the presence of proteins (nitrotyrosine, NOx-2 and NOx-4) involved in ROS generation were evaluated with dihydroethidium (DHE) fluorescence and by Western blotting, respectively. Results Chronic administration of sodium nitrite for two weeks to mice with angiotensin II-induced hypertension decreased systolic arterial blood pressure, reversed endothelial dysfunction, increased plasma nitrite level as well as vascular cGMP content. In addition, sodium nitrite treatment also decreased the elevated nitrotyrosine and NOx-4 protein level in angiotensin II-infused hypertensive mice. Conclusions The present study demonstrates that chronic treatment of hypertensive mice with sodium nitrite improves impaired endothelium function in conduit and resistance vessels in addition to its antihypertensive effect, partly through inhibition of ROS production.