Figure 5.

Potential mechanisms of the cross-talk between AT₁ receptors (AT₁Rs) and cannabinoid type 1 receptors (CB₁Rs) in the paraventricular nucleus of the hypothalamus. AT₁R activation increases blood pressure and heart rate due to a direct and indirectly mediated increase in glutamate (Glu) release. The indirect effect involves an inhibitory γ-aminobutyric acid (GABA) interneuron. In detail, AT₁R activation increases the release of endocannabinoids (mainly 2-arachidonoyl-glycerol) acting at presynaptic cannabinoid CB₁ receptors (CB₁Rs), activation of which decreases the inhibitory influence of GABA on sympathoexcitatory glutamatergic neurons. On the other hand, the CB₁R antagonist AM251 blocking presynaptic CB₁Rs increases the inhibitory influence of GABA on glutamatergic neurons excited by AT₁R activation, resulting in a decreased Ang II-induced pressor response. Facilitatory influences are shown by green arrows and plus signs, whereas inhibitory effects are represented by red bars and minus signs.