GABA‐A receptors mediating sympathoinhibition elicited by moxonidine in rats

Abstract

The sympathoinhibition elicited by moxonidine has been attributed to activation of α2‐adrenergic/imidazoline receptors in the rostral ventrolateral medulla (RVLM) and, more recently, in the nucleus of the solitary tract (NTS). In the present study, we aimed to determine the role of the γ‐aminobutyric acid (GABA) mechanisms in the commissural NTS (cNTS) in mediating anti‐hypertensive effects of moxonidine in anesthetized normotensive rats. Mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (sSNA) were recorded in urethane anaesthetized and artificially ventilated male Wistar rats (280–320 g, n = 5–7). Injections of moxonidine (2.5 and 5 nmol/50 nl) into the cNTS reduced resting MAP (105 ± 3 and 95 ± 5 mmHg, vs. pre‐injection: 117 ± 4 mmHg) and resting sSNA (92 ± 1 and 82 ± 3% of the control). The pre‐treatment with the GABA‐A antagonist bicuculline (25 pmol/50 nl) in the cNTS blocked the hypotension (Δ = −2 ± 3 mmHg, vs. moxonidine: Δ = −22 ± 4 mmHg) and sympathoinhibition (Δ = −1 ± 2%, vs. moxonidine: Δ = −18 ± 3%; p<0.05) elicited by moxonidine‐injected (5 nmol/50 nl) in the cNTS. These current data suggest that GABAergic mechanisms in the cNTS are essential for the sympathoinhibition and hypotension of moxonidine.Financial support: FAPESP; CNPq; CAPES.