TOTUM-854 REDUCTION OF BLOOD PRESSURE IS ASSOCIATED WITH AN ANTI-OXIDATIVE EFFECT IN SHR RATS

Abstract

Objective: Arterial Hypertension (AHT) is a major cause of premature death worldwide. We have developed Totum-854 (T-854), a polyphenol-rich botanical composition to reduce the risk of developing AHT. We assessed the acute and chronic effects on blood pressure in spontaneous hypertensive rats (SHR). Design and method: Acute protocol: 12-week-old SHR rats received a dose of vehicle or T-854 (1250 mg/kg) per os with a 48h-wash-out interval between two gavages, in random order. Chronic study: 18-week-old SHR rats received vehicle or T-854 (1000 mg/kg) per os once a day for 8 weeks. Arterial pressure was recorded during 24 h post-gavage (acute protocol) and for 2 hours once a week (chronic protocol) with a radio-telemetry device (HD-S10, DSI) directly implanted into the abdominal aorta. Results: Acute supplementation with T-854 induced a reduction in SBP and DBP during the 24 h recording after gavage in comparison to vehicle, with 24h-AUC decreased by 93.6mmHg.h ± 67.8mmHg.h and 70.8mmHg.h ± 54.6mmHg.h respectively. When T-854 was administered chronically, SBP and DBP were decreased from the 4th week after the start of supplementation in comparison to vehicle group. This reduction was maintained in the last weeks, with blood pressure values around baseline in T-854 SHR rats. Tissue analysis showed a plasma SOD activity increase and a decrease of aorta media thickness after 8-weeks T-854 supplementation, suggesting a potential protector role of T-854 on oxidative stress and vascular function. Conclusions: T-854 24h-post-gavage acute effect on blood pressure in hypertensive SHR rats suggests a rapid effect, with a decrease in blood pressure few hours after oral administration, and maintained during the time of the experiment. Moreover, T-854 prevents the development of AHT in SHR supplemented during eight weeks. In conclusion, T-854 appears as an efficient strategy to prevent AHT.