Pattern of sympathetic vasomotor activity induced by GABAergic inhibition in the brain and spinal cord

• Published in: Pharmacological reports 2020-02, Vol.72 (1), p.67-79
• Main Authors: Milanez, Maycon I. O., Silva, Adilson M., Perry, Juliana C., Faber, Jean, Nishi, Erika E., Bergamaschi, Cássia T., Campos, Ruy R.
• Format: Article
• Language: English
• Subjects: Drug Safety and Pharmacovigilance; Medicine; Pharmacotherapy; Pharmacy
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1007/s43440-019-00025-w

Background Knowledge of the central areas involved in the control of sympathetic vasomotor activity has advanced in the last few decades. γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammal nervous system, and a microinjection of bicuculline, an antagonist of GABA type A (GABA-A) receptors, into the paraventricular nucleus of the hypothalamus (PVN) alters the pattern of sympathetic activity to the renal, splanchnic and lumbar territories. However, studies are needed to clarify the role of GABAergic inputs in other central areas involved in the sympathetic vasomotor activity. The present work studied the cardiovascular effects evoked by GABAergic antagonism in the PVN, RVLM and spinal cord. Methods and results Bicuculline microinjections (400 pMol in 100 nL) into the PVN and rostral ventrolateral medulla (RVLM) as well as intrathecal administration (1.6 nmol in 2 µL) evoked an increase in blood pressure, heart rate, and renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively), inducing a higher coherence between rSNA and sSNA patterns. However, some of these responses were more intense when the GABA-A antagonism was performed in the RVLM than when the GABA-A antagonism was performed in other regions. Conclusions Administration of bicuculline into the RVLM, PVN and SC induced a similar pattern of renal and splanchnic sympathetic vasomotor burst discharge, characterized by a low-frequency (0.5 Hz) and high-amplitude pattern, despite different blood pressure responses. Thus, the differential control of sympathetic drive to different targets by each region is dependent, in part, on tonic GABAergic inputs.