Mechanistic insights into the role of inorganic nitrite in vasodilation of isolated aortic rings and formation of S‐nitrosoproteins

Abstract

Background The prevalence and relevance of arterial hypertension is still increasing. Inorganic nitrite (NO2-), which symbolizes a dietary antihypertensive agent, is still not completely understood in its metabolism and effects on the vascular system. The present study aims to understand how nitrite differs in its mode of action from common vasodilators in isolated aortic rings and which metabolic processes are caused through acute application. Methods and results Isolated aortic rings from rats were treated ex vivo with radial donors like hydrogen peroxide, peroxynitrite donor Sin-1 and hypochlorous acid and their relaxation ability by acetylcholine (ACh) and nitrite was juxtaposed. Vasodilation property of the thoracic aorta was also examined in a model of arterial hypertension via high-dose angiotensin-II (1mg/kg/d for 1 week, s.c.). It was found that nitrite retains its vasodilatory potency even when oxidants are used, in contrast to acetylcholine. However, induced hypertension resulted in an equally impaired ACh- and NO2-response.For evaluation of the effectiveness of nitrite in vivo oral gavage in conventional and germfree mice was performed. The acute therapy showed no relevant effect on vascular function while nitrite application resulted in increased formation of S-nitrosoproteins only in conventional raised mice. Conclusion Despite established pharmacological treatment, inorganic nitrite represents a dietary therapy option for arterial hypertension. Nitrite was shown to be a potent vasodilator which most probably affects all vessel layers and might compensate short-term oxidative stress better than common vasodilators like acetylcholine. In addition, the gastrointestinal flora seems to play a key role in nitrite metabolism and bioactivation. All in all, inorganic nitrite shows interesting properties that also appear to be accessible to a broad population, which is why further large-scale clinical studies about the cardiovascular effects, in particular in arterial hypertension, should be initiated.