Fig. 7.

Schematic presentation of the functional dependence of central CB₁R-mediated pressor response on brainstem OX₁R/orexin-A signaling. Central CB₁R (WIN55,212-2) or OX₁R (orexin-A) activation increases blood pressure in conscious freely moving rats (Figs. 3–5), and central CB₁R activation increased RVLM orexin-A level (Figs. 4 and 5) and enhances ERK1/2 and nNOS phosphorylation in the RVLM (Fig. 6). The proposed model system is further supported by our previous neurochemical and pharmacological findings following intracisternal or intra-RVLM microinjection of the CB₁R agonist WIN55,212-2 (Ibrahim and Abdel-Rahman, 2011, 2012a, 2012b), which implicated ERK1/2 and nNOS phosphorylation and enhanced NO generation in the RVLM in WIN55,212-2 evoked pressor response. Solid arrows indicate findings based on our current and previous studies, while dashed arrows indicate proposed signaling based on reported in vitro findings, but not tested in this model (see text for details).