l-Cysteine and l-AP4 microinjections in the rat caudal ventrolateral medulla decrease arterial blood pressure

The thiol amino acid l-cysteine increases arterial blood pressure (ABP) when injected into the cerebrospinal fluid space in conscious rats, indicating a pressor response to centrally acting l-cysteine. A prior synaptic membrane binding assay suggests that l-cysteine has a strong affinity for the l-2-amino-4-phosphonobutyric acid (l-AP4) binding site. The central action of l-cysteine may be via l-AP4 sensitive receptors. The present study investigated cardiovascular responses to l-cysteine and l-AP4 microinjected into the autonomic area of the caudal ventrolateral medulla (CVLM) where inhibitory neurons regulate ABP via pre-sympathetic vasomotor neurons. Both the injection of l-cysteine and l-AP4 in the CVLM sites identified with l-glutamate produced the same depressor and bradycardic responses in urethane-anesthetized rats. Neither a prior antagonist microinjection of MK801 for the N-methyl-d-aspartate (NMDA) receptor nor CNQX for the non-NMDA receptor attenuated the responses to l-cysteine, but the combination of the two receptor blocking with an additional prior injection abolished the response. In contrast, either receptor blockade alone abolished the response to l-AP4, indicating distinct mechanisms between responses to l-cysteine and l-AP4 in the CVLM. The results indicate that the CVLM is a central active site for l-cysteine's cardiovascular response. Central l-cysteine's action could be independent of the l-AP4 sensitive receptors. Cardiovascular regulation may involve endogenous l-cysteine in the CVLM. Further multidisciplinary examinations are required to elaborate on l-cysteine's functional roles in the CVLM.