Journal
NEUROSCIENCE LETTERS
Volume 728, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2020.134976
Keywords
Spinal GABA-A receptor; Spinal AT1 receptor; Renal sympathetic nerve; Splanchnic sympathetic nerve; Renovascular hypertension
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Funding
- FAPESP [18/01898-4, 2018/02671-3]
- CNPq [309020/2017-4]
- CAPES [001]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [18/01898-4] Funding Source: FAPESP
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Previous studies have been described changes in brain regions contributing to the sympathetic vasomotor overactivity in Goldblatt hypertension (2K1C). Furthermore, changes in the spinal cord are also involved in the cardiovascular and autonomic dysfunction in renovascular hypertension, as intrathecal (i.t) administration of Losartan (Los) causes a robust hypotensive/sympathoinhibitory response in 2K1C but not in control rats. The present study evaluated the role of spinal gamma-aminobutyric acid (GABA)-ergic inputs in the control of sympathetic vasomotor activity in the 2K1C rats. Hypertension was induced by clipping the renal artery. After six weeks, a catheter (PE-10) was inserted into the subarachnoid space and advanced to the T10-11 vertebral level in urethane-anaesthetized rats. The effects of i.t injection of bicuculline (Bic) on blood pressure (BP), renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively) were evaluated over 40 consecutive minutes in the presence or absence of spinal AT1 antagonism. I.t. Bic triggered a more intense pressor and sympathoexcitatory response in 2K1C rats, however, these responses were attenuated by previous i.t. Los. No differences in the gene expression of GAD 65 and GABA-A receptors subunits in the spinal cord segments were found. Thus, the sympathoexcitation induced by spinal GABA-A blockade is dependent of local AT1 receptor in 2K1C but not in control rats. Excitatory angiotensinergic inputs to sympathetic preganglionic neurons are tonic controlled by spinal GABAergic actions in Goldblatt hypertension.
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