PS-B03-8: ORAL CANNABIDIOL REDUCES ARTERIAL BLOOD PRESSURE DURING EARLY PHASE METABOLIC SYNDROME IN OLETF RATS

Abstract

Objective: Cardiovascular disease (CVD) is the leading cause of death in the U.S. and a primary outcome of metabolic syndrome (MetS). MetS is diagnosed by the presentation of at least 3 of the 6 conditions including abdominal obesity, elevated arterial pressure, and glucose intolerance ± insulin resistance. Identifying the root cause of these conditions individually is difficult but developing new treatments, which can ameliorate the multiple conditions of MetS has greater potential to reduce later-onset CVD. The benefits of cannabidiol (CBD) is widely recognized for potent anti-inflammatory and antioxidative properties, which may be cardioprotective during isolated risk factor conditions. However, these effects have not been examined during MetS conditions. Design: A cohort of 14-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were administered 175 mg CBD/kg by oral gavage for 5 weeks (CBD; n = 8). Animals were fed ad libitum and monitored alongside vehicle-treated OLETF (OLETF; n = 8) and vehicle-treated Long-Evans Tokushima Otsuka (LETO) rats, the lean-strain controls (LETO; n = 8). Rats were implanted with biotelemeters to chronically measure arterial pressure [DSI; HD-S10]. An oral glucose tolerance test (oGTT) was performed after 5 weeks of treatment. Results: CBD reduced arterial pressure within the first week of dosing (6 ± 1.4 mmHg or 4.1%; p < 0.05) and, after 5 weeks, by 9.7 ± 1.7 mmHg (6.5%; p < 0.05) from baseline. CBD blunted body mass gain and reduced abdominal adiposity by 39% (p < 0.0001) compared to untreated OLETF. Additionally, glucose absorption (AUCglucose 10 minutes after glucose bolus) was reduced 21% (p < 0.01) and enhanced uptake (slope 60 minutes to 120 minutes after glucose bolus) by 160% (p < 0.05). However, neither glucose response overall nor static fasting blood glucose were improved. On the other hand, insulin response (AUCinsulin) was reduced 77% (p < 0.0001) compared to OLETF, which ultimately reduced calculated insulin resistance index (IRI) of 79% (p < 0.0001). Moreover, CBD treatment reduced fasting plasma insulin by 76% compared to OLETF (p < 0.001). CBD decreased adiposity by 59% (p < 0.0001) associated with reduced plasma leptin. Conclusions: A chronic, high dose of CBD reduced the MetS-associated hypertension and other cluster factors. The renin-angiotensin-aldosterone system is a known driver of hypertension in humans with MetS and in the OLETF rat model and could be directly or indirectly modulated by CBD (analysis on-going). Collectively, CBD could be a novel and effective intervention strategy for early-stage hypertension and other metabolic risk factors associated with MetS.