Abstract

The ventral medial prefrontal cortex (vMPFC) facilitates the cardiac baroreflex response through N-methyl-d-aspartate (NMDA) receptor activation and nitric oxide (NO) formation by neuronal NO synthase (nNOS) and soluble guanylate cyclase (sGC) triggering. Glutamatergic transmission is modulated by the cannabinoid receptor type 1 (CB₁) and transient receptor potential vanilloid type 1 (TRPV₁) receptors, which may inhibit or stimulate glutamate release in the brain, respectively. Interestingly, vMPFC CB₁ receptors decrease cardiac baroreflex responses, while TRPV₁ channels facilitate them. Therefore, the hypothesis of the present study is that the vMPFC NMDA/NO pathway is regulated by both CB₁ and TRPV₁ receptors in the modulation of cardiac baroreflex activity. In order to test this assumption, we used male Wistar rats that had stainless steel guide cannulae bilaterally implanted in the vMPFC. Subsequently, a catheter was inserted into the femoral artery, for cardiovascular recordings, and into the femoral vein for assessing baroreflex activation. The increase in tachycardic and bradycardic responses observed after the microinjection of a CB₁ receptors antagonist into the vMPFC was prevented by an NMDA antagonist as well as by the nNOS and sGC inhibition. NO extracellular scavenging also abolished these responses. These same pharmacological manipulations inhibited cardiac reflex enhancement induced by TRPV₁ agonist injection into the area. Based on these results, we conclude that vMPFC CB₁ and TRPV₁ receptors inhibit or facilitate the cardiac baroreflex activity by stimulating or blocking the NMDA activation and NO synthesis.