Background/Objectives: Vascular calcification is a major contributor to cardiovascular mortality and disability. Here, we investigated whether dietary nitrate, an exogenous source of nitric oxide (NO), could inhibit vascular calcification in a rat model induced by excess vitamin D3. Methods: The rats were injected subcutaneously with phosphate-buffered saline or 200,000 IU/kg cholecalciferol and the abdominal aorta was isolated 7 and 14 d after injection. Results: Von Kossa staining revealed mild vascular calcification 7 d after injection, with the positive area expanding by 14 d. Vasorelaxation induced by the NO donor sodium nitroprusside was normal 7 d after injection but weakened 14 d after injection. In a separate experiment, sodium nitrate (3 or 10 mM in drinking water) was administered for the last 7 and 13 d, prior to sacrifice, 14 d after cholecalciferol injection. Von Kossa staining-positive areas and calcium content in the abdominal aortas did not decrease with short-term administration of sodium nitrate but decreased with long-term administration; no difference in effect based on dosage was observed in either short-term or long-term administration. Low-dose sodium nitrate tended to increase plasma nitrite and nitrate levels, which are indicators of NO bioavailability, similar to both short- and long-term administration, which increased significantly at higher doses. Conclusions: These findings suggest that NO homeostasis in blood vessels deteriorates with the progression of vascular calcification, and that dietary nitrate may be a useful therapeutic approach.
Tawa et al. (2026) studied this question.