Central cardiovascular actions of L-homocysteine microinjected into ventrolateral medullary autonomic areas of the rat

摘要

Elevated l-homocysteine concentrations in the plasma and cerebrospinal fluid are related to cardiovascular and neuronal diseases, and could contribute to disease development. However, the central cardiovascular actions of l-homocysteine in two important autonomic regulating areas remain unknown: the rostral ventrolateral medulla (RVLM), including pre-sympathetic neurons, and the caudal ventrolateral medulla (CVLM), including interneurons projecting to pre-sympathetic neurons in the RVLM. Therefore, the aim of the current study was to examine the influence of l-homocysteine microinjected into the RVLM and CVLM areas on changes in arterial blood pressure (ABP) and heart rate (HR) of anesthetized rats, as well as the influence of ionotropic excitatory amino acid (iEAA) receptors on the central actions of l-homocysteine. l-Homocysteine solutions were microinjected into the RVLM and CVLM, which were defined according to pressor and depressor responses to l-glutamate microinjections, respectively. ABP and HR increased in the RVLM and decreased in the CVLM after microinjection with l-homocysteine, similar to l-glutamate, in a dose-dependent manner, suggesting mediation of EAA receptors. Prior microinjection of the N-methyl-d-aspartate (NMDA) iEAA receptor antagonist MK801, but not the non-NMDA receptor antagonist CNQX, abolished the observed responses to l-homocysteine in both the RVLM and CVLM. These results indicate the central cardiovascular actions of l-homocysteine via MK801-sensitive receptors of the medullary autonomic neurons in the rat RVLM and CVLM. It remains unknown if the central cardiovascular actions are related to cardiovascular diseases after endogenously and locally augmented l-homocysteine production by disordered metabolism. Further studies on functional significance of l-homocysteine may provide some clue to understand its toxic mechanism.