Role of cannabinoid receptor type1in rostral ventrolateralmedulla in high-fat diet-induced hypertension in rats

By: Guo-Qi Li, Zhe Wang, Tong Zhao, Shi-Xuan Dai, Jia-Ming Liu,
Bo-Zhi Jia, Yi Zhang, and Qian Li. Journal of Hypertension. 36(4):801–808, APR 2018.

One feature that describes obesity is hypertension, which is caused by an increased sympathetic nervous system. More specifically, the activity of the rostral ventrolateral medulla (RVLM) is increased. The RVLM plays an important role in regulating sympathetic activity. This region has been seen to contribute to the obesity-induced hypertension. This study focuses on the cannabinoid type 1 (CB1) receptor in the RVLM which has been shown to increase activity in the sympathetic nervous system when there is high expression. They hypothesized that CB1 receptor plays a critical role in the development of obesity induced hypertension. To test this, two major endocannabinoids were evaluated, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), for expression in the RVLM, then examined for their role in regulation of BP, HR, and renal sympathetic activity (RSNA).

Microinjections were performed on the rats (4-6 weeks old). One group received unilateral RVLM injections of saline and 100nM/0.5ul AM251 (a selective cannabinoid CB1 receptor antagonist). The second group received unilateral RVLM injection of saline and 500nM/0.5ul AM251. BP, HR, and RSNA were monitored for 1 h followed by a second microinjection after 30 min. Western blotting was used to examine CB1 receptor protein levels in RVLM. To examine levels of AEA and 2-AG, separate groups of rats were used for quantification. Following the experiments, rats were euthanized and the brains were sectioned.

The results showed that rats with a high fat diet were found to have an increased BP, HR, and basal RSNA. As for the CB1 receptor, it was found that the levels of the two endocannabinoids was enhanced in high fat diet (HFD) rats. The protein level was also enhanced.

The role of CB1 in the RVLM was shown to have increased levels. The RVLM microinjections of AM251 showed decreased BP, HR, and RSNA in HFD rats, which suggest that CB1 receptor mediated neurotransmission might be increased in RVLM in the HFD rats. Previous studies have shown that an expression of CB1 receptor in the RVLM is higher in hypertensive rats. CB1 receptor antagonists lowered BP much more in hypertensive rats, which explains the importance of these receptors to the contributions to BP regulation.

This study drew interest from myself due to the important contribution of cannabinoid receptor in the RVLM. I had no idea this type of receptor existed in the RVLM, which goes to show how many different inputs the RVLM receives and converts into an output on sympathetic activity.

-Tsetse Fly