title: Overactivation of cannabinoid receptor type 1 in rostral ventrolateral medulla promotes cardiovascular responses in spontaneously hypertensive rats.
abstract: Stimulation of cannabinoid type 1 (CB1) receptor in the rostral ventrolateral medulla (RVLM) increases renal sympathetic nerve activity (RSNA) and blood pressure (BP) in rats. Thus, we hypothesized that abnormal expression of CB1 receptor in the RVLM may play a critical role in the pathogenesis of essential hypertension.
  
  
  
  We evaluated the effects of intra-RVLM infusions of arachidonyl-2'-chloroethylamide (ACEA), selective CB1 receptor agonist, with or without AM251, selective CB1 receptor antagonist, on BP, heart rate (HR), and RSNA in spontaneously hypertensive rats and wild-type rats. We also assessed the protein level and surface expression of CB1 receptor in the RVLM in these rats.
  
  
  
  We found that spontaneously hypertensive rats exhibited higher basal BP, HR, and RSNA than wild-type rats. Furthermore, unilateral intra-RVLM microinjections ACEA (0, 10, or 100 nM/0.5 μl/site) increased BP, HR, and RSNA to a greater extent in spontaneously hypertensive rats than in wild-type rats. These effects were abolished by co-administrations of AM251 (500 nM/0.5 μl/site) into the RVLM. In addition, the protein level of CB1 receptor in the RVLM was robustly increased in spontaneously hypertensive rats, which is correlated with ACEA-induced maximum changes of RSNA, and this was also associated with reduced expression of β-arrestin 2 in the RVLM in spontaneously hypertensive rats. Finally, overexpression of β-arrestin 2 in the RVLM in spontaneously hypertensive rats attenuated BP, HR and RSNA.
  
  
  
  Taken together, our results suggested that alterations of CB1 receptor desensitization in the RVLM may play a role in the pathogenesis of essential hypertension.
authors.affiliation: aDepartment of Physiology, Hebei Medical University bDepartment of Cardiology, Third Hospital of Hebei Medical University cHebei Collaborative Innovation Center for Cardio-cerebrovascular Disease dDepartment of Otolaryngology, Hebei General Hospital, Shijiazhuang, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Guo-Qi
authors.initials: GQ
authors.lastname: Li
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D000075222:Essential Hypertension; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000294:innervation; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism*; D008845:Microinjections; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D000071560:beta-Arrestin 2 / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; C000605257:Arrb2 protein, rat; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C119325:arachidonyl-2-chloroethylamide; D000071560:beta-Arrestin 2; C103505:AM 251