Therapeutic Implications of Nitrite in Hypertension

Abstract

Nitrite, an anion produced from the oxidative breakdown of nitric oxide (NO), has traditionally been viewed as an inert molecule. However, this dogma has been challenged with the findings that nitrite can be readily reduced to NO under pathological conditions, hence representing a physiologically relevant storage reservoir of NO either in the blood or tissues. Nitrite administration has been demonstrated to improve myocardial function in subjects with heart failure and to lower the blood pressure in hypertensive subjects. Thus, extensive amount of work has since been carried out to investigate the therapeutic potential of nitrite in treating cardiovascular diseases, especially hypertension. Studies done on several animal models of hypertension have demonstrated the efficacy of nitrite in preventing and ameliorating the pathological changes associated with the disease. This brief review of the current findings aims to re-evaluate the use of nitrite for the treatment of hypertension and in particular to highlight its role in improving endothelial function.

Study on the Mechanism of the Danggui–Chuanxiong Herb Pair on Treating Thrombus through Network Pharmacology and Zebrafish Models

“…Nitric oxide (NO) and nitrite are the intermediate metabolites in nitrogen metabolism. Nitrite can be converted into NO under pathological conditions and therefore represents a physiologically relevant NO capacity in blood or tissue . NO produced physiologically has a useful function in the cardiovascular system, including controlling the vascular tone, leukocyte adhesion, and platelet aggregation. , In addition, NO also has anti-inflammatory and antioxidant effects. , The T cell receptor signaling pathway is the vital regulated pathway because it controls the oxygen diffusion to the central part of the heart …”

“…Nitrite can be converted into NO under pathological conditions and therefore represents a physiologically relevant NO capacity in blood or tissue. 39 NO produced physiologically has a useful function in the cardiovascular system, including controlling the vascular tone, leukocyte adhesion, and platelet aggregation. 40,41 In addition, NO also has anti-inflammatory and antioxidant effects.…”

Redox Switches Controlling Nitric Oxide Signaling in the Resistance Vasculature and Implications for Blood Pressure Regulation: Mid-Career Award for Research Excellence 2020

“…NO is known to be a potent vasodilator and regulator of blood pressure, and its endogenous anionic oxidation products, nitrate and nitrite, are increasingly demonstrating antihypertensive activity. [131][132][133] The nitrate-nitrite-NO bioconversion cascade is central to the blood pressure effects of nitrate-nitrite therapies. Nitrate's antihypertensive activity requires its reduction to nitrite, which largely occurs via oral commensal bacteria after ingestion of nitrate-rich foods, such as leafy green vegetables or beetroot.…”

The Skeletal Muscle, the Heart, and the Liver Are the Major Organs of the Accumulation of Nitric Oxide Metabolites after Oral Nitrite Treatment

“…While many studies have shown the biological significance of NO metabolites at physiological levels [ 7 , 8 ], evidence has accumulated supporting the idea that pharmacological approaches aimed at increasing their tissue concentrations can lead to beneficial effects in various pathological conditions [ 9 , 10 ]. In this context, the oral administration of nitrite leads to increases in plasma concentrations of nitrite, nitrate, and S-nitrosothiols, accompanied by corresponding elevations in NO metabolite concentrations across various organs at different time frames [ 11 , 12 ].…”