Abstract 10461: Totum-854 Lowers Blood Pressure in L-NAME-Induced Arterial Hypertension in Mice and in Spontaneous Hypertensive Rat Model

Introduction: 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 chronic effect of T-854 on preventing the development of L-NAME-induced AHT in mice, and the acute effect on blood pressure in spontaneous hypertensive rats (SHR). Methods: 12-week-old C57Bl6/J mice were divided into Control, L-NAME, and L-NAME + T-854 group. L-NAME (100 mg/kg/day) was dissolved in drinking water. Mice received either T-854 (450 mg/kg) or vehicle by gavage once a day for three weeks . The arterial pressure was assessed using the CODA® Tail-Cuff System every week for three weeks. 12-week-old SHR rats received a dose of vehicle or T-854 (1250mg/kg) per os with a 48h-wash-out interval between two gavages, in random order. Arterial pressure was recorded during 24h post-gavage with a radio-telemetry device (HD-S10, DSI) directly implanted into the abdominal aorta. Results: In mice, 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 MBP from the second week of supplementation. After three weeks, 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. In the SHR study, SBP and DBP were reduced during 24h recording after T-854 gavage in comparison to vehicle, with a 24h-AUC decreased by 108 ± 87.8 and 84.4 ± 69.3 mmHg.h, respectively. Conclusions: In conclusion, T-854 appears as an efficient strategy to prevent AHT and this effect was confirmed in two different preclinical models: L-NAME-induced AHT in mice and SHR rats.