TOTUM-854 PREVENTS L-NAME-INDUCED ARTERIAL HYPERTENSION IN MICE. (April 2021)

• Record Type: Journal Article
• Authors: Bolea, Gaetan; Ripoche, Doriane; Meyer, Gregory; Lejoubioux, Florian; Michaux, Arnaud; Otero, Yolanda; Peltier, Sebastien; Sirvent, Pascal; Reboul, Cyril
• Is Part Of: Journal of hypertension. Volume 39(2021)e-Supplement 1
• Publication Date: 2021-04
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000749120.67773.cb
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: Arterial Hypertension (HTA) is a major cause of premature death worldwide, with an estimated global prevalence of 1.13 billion people. Polyphenolic compounds have been shown promising effects in the context of HTA management. We have developed Totum-854 (T-854), a polyphenol-rich botanical composition to reduce the risk of developing AHT. We assessed the chronic effect of T-854 on preventing the development of N(G)-Nitro-L-arginine-methyl ester (L-NAME)-induced AHT in mice. Figure. No caption available. Design and method: Twelve-week-old C57Bl6/J mice were divided into 3 groups: Control (n = 11), L-NAME (n = 11), and L-NAME + T-854 (n = 11). L-NAME (100 mg/kg/day) was dissolved in drinking water. Mice were gavaged once a day for three weeks with either T-854 (450 mg/kg) or vehicle. The arterial pressure was assessed using the CODA® Tail-Cuff System every week for three weeks. Effects of T-854 on in vitro angiotensin-converting enzyme (ACE) activity was also assessed by a HPLC-UV method. Results: Body weight evolution was not significantly different between the 3 groups over the study period. As expected, L-NAME increased systolic (SBP; from 105 ± 3 to 130 ± 1 mmHg, p < 0.0001), diastolic (DBP; from 77 ± 3 to 97 ± 2 mmHg, p < 0.0001) and mean (MBP; from 86 ± 3 to 108 ± 2 mmHg, p < 0.0001) blood pressure along the 3 weeks of treatment. Interestingly, in T-854-supplemented mice, SBP was significantly reduced from the first week of supplementation and DBP and MDP from the second week of supplementation. After three weeks of supplementation, T-854 lowered the SBP by 16% (p < 0.0001), the DBP by 20% (p < 0.05) and the MBP by 18 % (p < 0.01), in comparison to L-NAME mice. Moreover, in vitro experiments showed an inhibitory effect of T-854 on ACE activity. Conclusions: In conclusion, this study showed that T-854 prevents L-NAME-induced HTA in mice. ACE inhibition may partly explain the preventive effects of T-854 on HTA development in this model. T-854 is a promising new approach for the prevention of HTA.