Preventive effects of nitrate-rich beetroot juice supplementation on monocrotaline-induced pulmonary hypertension in rats

Abstract

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.

Effects of ESC/ESH-Based Written Lifestyle Advice including a Nutraceutical on 24-Hour Blood Pressure in High-Normal Blood Pressure Patients with Low Cardiovascular Risk

“…The known "regression to the mean" effect can also have a role. Alongside more adherence to lifestyle advice than the younger group, different arterial responses to vasodilating stimuli by restoring endothelial function and enhancing NO bioavailability could have brought out this additional finding, as reported by recent experimental and clinical investigations [28][29][30]. Thus, middle-aged pre-hypertensive and non-smoking patients could be the preferable target of this approach based on generic lifestyle advice and nitrate supplementation [27].…”

Effects of beetroot juice supplementation on vascular functional and structural changes in aged mice

“…The aged mice used in this study also showed pronounced medial thickening without affecting the lumen diameter, implying the occurrence of outward hypertrophic remodeling. As BRJ supplementation has beneficial effects on vascular wall thickening (Morselli et al, 2021;Tawa et al, 2021Tawa et al, , 2022, we expected that age-related vascular remodeling would also be suppressed in this study. However, BRJ supplementation did not reverse the medial thickening observed in aged mice.…”

Ameliorative Effects of Beetroot Juice Supplementation on Monocrotaline-Induced Pulmonary Hypertension in Rats

“…Importantly, MCT is metabolized in the liver to an active metabolite that induces such toxic effects [23]. Although we previously reported that starting BRJ supplementation at the same time as MCT injection improves PH symptoms, including RV hypertrophy, RVSP elevation, and pulmonary vascular remodeling [18], BRJ ingestion may have suppressed this metabolic conversion rather than prevented disease progression. Therefore, this study, which shows definite ameliorative effects of BRJ supplementation on PH, is of great significance.…”

“…Supplementations were started 1 week (7 days) after saline or MCT injection and were maintained for an additional three weeks (21 days). BRJ (Beet It Organic Shot) was obtained from James White Drinks Ltd. (Ipswich, UK); the dilution factors were determined based on our previous study [18]. The solutions were changed every 1-2 days.…”

“…2022, 2 548 disease [16]. We recently reported that beetroot juice (BRJ) supplementation from the day of monocrotaline (MCT) injection prevents the development of PH in a nitrate-dependent manner in a rat model of PH [17,18]. However, BRJ supplementation from 2 week (14 days) after MCT injection did not improve PH in the same model [17].…”