Abstract
Arterial hypertension is one of the major health risk factors leading to coronary artery disease, stroke or peripheral artery disease. Dietary uptake of inorganic nitrite (NO2−) and nitrate (NO3−) via vegetables leads to enhanced vascular NO bioavailability and provides antihypertensive effects. The present study aims to understand the underlying vasoprotective effects of nutritional NO2− and NO3− co-therapy in mice with angiotensin-II (AT-II)-induced arterial hypertension. High-dose AT-II (1 mg/kg/d, 1w, s. c.) was used to induce arterial hypertension in male C57BL/6 mice. Additional inorganic nitrite (7.5 mg/kg/d, p. o.) or nitrate (150 mg/kg/d, p. o.) were administered via the drinking water. Blood pressure (tail-cuff method) and endothelial function (isometric tension) were determined. Oxidative stress and inflammation markers were quantified in aorta, heart, kidney and blood. Co-treatment with inorganic nitrite, but not with nitrate, normalized vascular function, oxidative stress markers and inflammatory pathways in AT-II treated mice. Of note, the highly beneficial effects of nitrite on all parameters and the less pronounced protection by nitrate, as seen by improvement of some parameters, were observed despite no significant increase in plasma nitrite levels by both therapies. Methemoglobin levels tended to be higher upon nitrite/nitrate treatment. Nutritional nitric oxide precursors represent a non-pharmacological treatment option for hypertension that could be applied to the general population (e.g. by eating certain vegetables). The more beneficial effects of inorganic nitrite may rely on superior NO bioactivation and stronger blood pressure lowering effects. Future large-scale clinical studies should investigate whether hypertension and cardiovascular outcome in general can be influenced by dietary inorganic nitrite therapy.
Highlights
Arterial hypertension represents a major cardiovascular risk factor that has been shown to be largely responsible for mortality and morbidity worldwide [1,2]
We observed a significantly higher systolic and diastolic arterial blood pressure in the AT-II-infused mice that was ameliorated by nitrite but not nitrate administration (Fig. 1A)
In the present study we sought to determine whether inorganic ni trite or nitrate improve the adverse cardiovascular phenotype in experimental arterial hypertension (AT-II-infusion for 7d)
Summary
Arterial hypertension represents a major cardiovascular risk factor that has been shown to be largely responsible for mortality and morbidity worldwide [1,2]. Research on the pathophysiology and especially the treatment of arterial hypertension considering non-pharmacological forms of therapy appears to be essential from a medical point of view. Nitrovasodilators such as organic nitrates, especially glycerol trini trate (GTN, known as nitroglycerin), are still widely used for the acute therapy of hypertensive crisis [7,8]. Chronic treatment is not recommended due to the development of nitrate tolerance [9,10] In this context, inorganic nitrite or nitrate administration represents an alternative, nutritional therapeutic option without tolerance induction but with most beneficial features of classical antihypertensive drugs [11,12,13]. Oral inorganic nitrate and nitrite intake causes increased arterial forearm blood flow, elevated plasma cGMP levels and less vascular stiffness [15,16,18]
Sign-in/Register to view highlights & summary 
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call