Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
Department of Pharmacology, Kanazawa Medical University, Kahoku, Ishikawa, Japan.
PLoS One. 2021 Apr 8;16(4):e0249816. doi: 10.1371/journal.pone.0249816. eCollection 2021.
Beetroot (Beta vulgaris L.) has a high level of nitrate; therefore, its dietary intake could increase nitric oxide (NO) level in the body, possibly preventing the development of pulmonary hypertension (PH). In this study, we examined the effects of beetroot juice (BJ) supplementation on PH and the contribution of nitrate to such effects using a rat model of monocrotaline (MCT, 60 mg/kg s.c.)-induced PH. Rats were injected subcutaneously with saline or 60 mg/kg MCT and were sacrificed 28 days after the injection. In some rats injected with MCT, BJ was supplemented from the day of MCT injection to the day of sacrifice. First, MCT-induced right ventricular systolic pressure elevation, pulmonary arterial medial thickening and muscularization, and right ventricular hypertrophy were suppressed by supplementation with low-dose BJ (nitrate: 1.3 mmol/L) but not high-dose BJ (nitrate: 4.3 mmol/L). Of the plasma nitrite, nitrate, and their sum (NOx) levels, only the nitrate levels were found to be increased by the high-dose BJ supplementation. Second, in order to clarify the possible involvement of nitrate in the preventive effects of BJ on PH symptoms, the effects of nitrate-rich BJ (nitrate: 0.9 mmol/L) supplementation were compared with those of the nitrate-depleted BJ. While the former exerted preventive effects on PH symptoms, such effects were not observed in rats supplemented with nitrate-depleted BJ. Neither supplementation with nitrate-rich nor nitrate-depleted BJ affected plasma nitrite, nitrate, and NOx levels. These findings suggest that a suitable amount of BJ ingestion, which does not affect systemic NO levels, can prevent the development of PH in a nitrate-dependent manner. Therefore, BJ could be highly useful as a therapy in patients with PH.
甜菜根（Beta vulgaris L.）的硝酸盐含量很高；因此，其饮食摄入可能会增加体内一氧化氮（NO）水平，从而可能预防肺动脉高压（PH）的发展。在这项研究中，我们使用了野百合碱（MCT，60mg/kg sc）诱导的 PH 大鼠模型，研究了甜菜根汁（BJ）补充对 PH 的影响以及硝酸盐对此类影响的贡献。大鼠皮下注射生理盐水或 60mg/kg MCT，并在注射后 28 天处死。在一些注射 MCT 的大鼠中，从 MCT 注射之日起至处死之日起补充 BJ。首先，低剂量 BJ（硝酸盐：1.3mmol/L）但不是高剂量 BJ（硝酸盐：4.3mmol/L）抑制了 MCT 诱导的右心室收缩压升高、肺动脉中层增厚和肌化以及右心室肥厚。在血浆亚硝酸盐、硝酸盐及其总和（NOx）水平中，只有高剂量 BJ 补充增加了硝酸盐水平。其次，为了阐明硝酸盐在 BJ 对 PH 症状的预防作用中的可能作用，比较了富含硝酸盐的 BJ（硝酸盐：0.9mmol/L）补充与硝酸盐耗尽的 BJ 的补充作用。前者对 PH 症状有预防作用，但硝酸盐耗尽的 BJ 补充则未观察到这种作用。富含硝酸盐或硝酸盐耗尽的 BJ 补充均不影响血浆亚硝酸盐、硝酸盐和 NOx 水平。这些发现表明，适量摄入不会影响全身 NO 水平的 BJ，可以以硝酸盐依赖的方式预防 PH 的发展。因此，BJ 可能非常有助于 PH 患者的治疗。
