Chronic Low Dose Δ⁹-Tetrahydrocannabinol Administration Prevents Functional and Electrophysiological Myocardial Changes in SHR and SHR/STZ Rats by Antioxidant and Anti-inflammatory Mechanisms

It is well established that oxidative stress and inflammation initiate cardiovascular dysfunction associated with poorly managed hypertension and diabetes. The aim of this study was to examine the antioxidant, anti-inflammatory and cardio-protective effects of Δ⁹-Tetrahydrocannabinol (T) (0.15 mg/kg/day for eight weeks) in two-month-old spontaneously-hypertensive (SHR) and spontaneously-hypertensive-diabetic (SHR/STZ) rats. Rats were randomly assigned to a treatment group and WKY rats were used as controls. SHR and SHR/STZ rats displayed elevated blood pressure, decreased serum levels of nitric-oxide (NO) and increased serum malondialdehyde and IL-1β concentrations. Electrophysiological and functional alterations in SHR and SHR/STZ manifested as prolonged action potential duration at 20%, 50% and 90% (WKY 58.81 ± 3.15; SHR 97.87 ± 5.95*; SHR/STZ 123.64 ± 9.18*) of repolarisation, reduced developed and end systolic pressure and reduced rates of contraction and relaxation. T treatments did not decrease blood pressure but improved alterations in NO, MDA and IL-1β concentrations. Improvements in developed pressure, end systolic pressure and maximal rates of contraction (SHR 1078.33 ± 119.4*; SHR + T 1655.17 ± 125.42**; SHR/STZ 1488.0 ± 211.87; SHR/STZ + T 1813.33 ± 97.67) and relaxation as well as the attenuation of prolonged action potential durations at 20%, 50% and 90% (SHR + T 75.23 ± 5.69**; SHR/STZ + T 94.36 ± 9.93^#) of repolarisation were observed in T treated SHR and SHR/STZ. These results support the hypothesis that increased oxidative stress, decreased serum NO and systemic inflammation play an integral role in the development of cardiovascular dysfunction in 16-week-old SHR and 16-week-old SHR with eight weeks of induced diabetes. Furthermore, low-dose, chronic, T treatment prevents electrophysiological and functional changes in the myocardium of SHR and SHR/STZ rats by antioxidant and anti-inflammatory mechanisms.