Medial prefrontal cortex N-methyl-D-aspartate receptor/nitric oxide/cyclic guanosine monophosphate pathway modulates both tachycardic and bradycardic baroreflex responses

Abstract

Neural reflex mechanisms, such as the baroreflex, are involved in regulating cardiovascular system activity. Previous results showed that the ventral portion of the medial prefrontal cortex (vMPFC) is involved in modulation only of the cardiac baroreflex bradycardic component. Moreover, vMPFC N-methyl-D-aspartate (NMDA) receptors modulate the bradycardia baroreflex, but the baroreflex tachycardic component has not been investigated. Furthermore, glutamatergic neurotransmission into the vMPFC is involved in activation of the cardiac sympathetic and parasympathetic nervous system. Finally, it has been demonstrated that glutamatergic neurotransmission into the vMPFC can be modulated by the endocannabinoid system and that activation of the CB1 cannabinoid receptor by anandamide, an endocannabinoid, can decrease both cardiac baroreflex bradycardic and tachycardic responses. Thus, there is the possibility that glutamatergic neurotransmission into the vMPFC does not modulate only the cardiac bradycardic component of the baroreflex. Therefore, the present study investigated whether glutamatergic neurotransmission into the vMPFC modulates both cardiac baroreflex bradycardic and tachycardic responses. We found that vMPFC bilateral microinjection of the NMDA receptor antagonist AP7 (4 nmol/200 nl), of a selective inhibitor of neuronal nitric oxide (NO) synthase N-propyl (0.08 nmol/200 nl), of the NO scavenger carboxy-PTIO (2 nmol/200 nl), or of the NO-sensitive guanylate cyclase ODQ (2 nmol/200 nl) decreased the baroreflex activity in unanesthetized rats. Therefore, our results demonstrate the participation of NMDA receptors, production of NO, and activation of guanylate cyclase in the vMPFC in the modulation of both cardiac baroreflex bradycardic and tachycardic responses.

Dorsal hippocampus cholinergic and nitrergic neurotransmission modulates the cardiac baroreflex function in rats

“…Stimulation of hippocampus may evoke BP and HR decrement, responses that are abolished by the inhibition of the MPFC (Ruit & Neafsey, ). The MPFC sends projections to brainstem areas related to cardiovascular tonic control (Fisk & Wyss, ; Vertes, ), and we demonstrated that MPFC modulates baroreflex function (Ferreira‐Junior et al, , ). Therefore, MPFC may be a relay area for hippocampal control in the baroreflex function once hippocampus has no direct projections to the brainstem (Cenquizca & Swanson, ).…”

“…The peripheral information about BP status is integrated into the solitary tract nucleus that projects to other brainstem areas as rostral and caudal ventrolateral medulla and vagal nuclei (Guyenet, ). However, supramedullary areas such as amygdala (Fortaleza, Ferreira‐Junior, Lagatta, Resstel, & Correa, ), medial prefrontal cortex (MPFC; Ferreira‐Junior, Fedoce, Alves, Correa, & Resstel, ; Ferreira‐Junior, Fedoce, Alves, & Resstel, ) and hippocampus (Ferreira‐Junior et al, , ) can modulate the baroreflex activity.…”

Hippocampal subareas arranged in the dorsoventral axis modulate cardiac baroreflex function in a site‐dependent manner in rats

“…Furthermore, the MPFC modulates baroreflex function (Ferreira‐Junior et al . , ). Therefore, the MPFC may be a part of the neural circuitry that allows the VH to modulate cardiac baroreflex function.…”

Multivariate analysis of subjective responses to d-amphetamine in healthy volunteers finds novel genetic pathway associations

“…Both acute DA and glutamate effects in rat brain, and the alteration of long-term potentiation via glutamatergic tone and metabotropic glutamate receptors are crucial to acute responses to psychostimulant drugs and addiction (Zhang, Loonam et al 2001), (Kalivas 2009). The ventral medial prefrontal cortex, with abundant glutamatergic transmission, is involved in modulating bradycardic/tachycardic reflexes (Ferreira-Junior, Fedoce et al 2013). Cardiac vagal preganglionic neurons are also responsible for heart rate modulation, and receive glutamatergic signaling input (Hildreth and Goodchild 2010).…”