1. Nitrite mediated vasorelaxation in human chorionic plate vessels is enhanced by hypoxia and dependent on the NO-sGC-cGMP pathway
- Author
-
Tropea, Teresa, Wareing, Mark, Greenwood, Susan L., Feelisch, Martin, Sibley, Colin P., and Cottrell, Elizabeth C.
- Subjects
Adult ,Dose-Response Relationship, Drug ,Sodium Nitrite ,Nitrite ,Placenta ,Imidazoles ,Nitric oxide ,Arteries ,Chorion ,Placental dysfunction ,Benzoates ,Article ,Veins ,Vasodilation ,Pregnancy ,Humans ,Female ,Hemoglobin ,Hypoxia ,Cyclic GMP ,Nitrites - Abstract
Adequate perfusion of the placental vasculature is essential to meet the metabolic demands of fetal growth and development. Lacking neural control, local tissue metabolites, circulating and physical factors contribute significantly to blood flow regulation. Nitric oxide (NO) is a key regulator of fetoplacental vascular tone. Nitrite, previously considered an inert end-product of NO oxidation, has been shown to provide an important source of NO. Reduction of nitrite to NO may be particularly relevant in tissue when the oxygen-dependent NO synthase (NOS) activity is compromised, e.g. in hypoxia. The contribution of this pathway in the placenta is currently unknown. We hypothesised that nitrite vasodilates human placental blood vessels, with enhanced efficacy under hypoxia. Placentas were collected from uncomplicated pregnancies and the vasorelaxant effect of nitrite (10−6–5x10−3 M) was assessed using wire myography on isolated pre-constricted chorionic plate arteries (CPAs) and veins (CPVs) under normoxic (pO2 ∼5%) and hypoxic (pO2 ∼1%) conditions. The dependency on the NO–sGC–cGMP pathway and known nitrite reductase (NiR) activities was also investigated. Nitrite caused concentration-dependent vasorelaxation in both arteries and veins, and this effect was enhanced by hypoxia, significantly in CPVs (P, Highlights • Nitrite has been shown to induce vasorelaxation in a number of vascular beds, with enhanced efficacy under hypoxia. • Here, we show that nitrite induces vasorelaxation also in isolated human placental blood vessels. • Our data suggest nitrite vasorelaxation in placental blood vessels is via nitrite->nitric oxide reduction. • The identity of the nitrite reductases responsible for the observed effects in this vascular bed remain unknown.
- Published
- 2018