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.
© 2011 Published by Elsevier Inc.