Elsevier

Brain Research

Volume 537, Issues 1–2, 24 December 1990, Pages 175-181
Brain Research

Evidence for clonidine presynaptically modulating amino acid release in the rostral ventral medulla: role in hypertension

https://doi.org/10.1016/0006-8993(90)90355-FGet rights and content

Abstract

Reports suggested that the predominant site of action for the antihypertensive effects of clonidine is the rostral ventrolateral medulla (RVL), the presumed tonic vasomotor center. This study examined whether clonidine directly interacts with nerve terminal α2-adrenergic receptors in the RVL to inhibit the release of sympathoexcitatory transmitters like glutamate (Glu) and aspartate (Asp), and/or facilitate the release of sympathoinhibitory transmitters like γ-aminobutyric acid (GABA). Release of GABA and Glu was measured from synaptosomes prepared from the rostral ventral medulla of spontaneously hypertensive rats (SHR), a genetic model of hypertension, and normotensive Wistar-Kyoto rats (WKY). Quantification of neurotransmitter release was performed by high-performance liquid chromatography. Depolarization with 35 mM K+ significantly increased by 58–110% the release of GABA, Glu and Asp; however, no strain differences were observed. In contrast, spontaneous release of GABA and Asp was significantly lower in SHR than that of WKY (−36 and −41%, respectively); this effect was not observed for Glu. Clonidine (1 and 10 μM) enhanced the spontaneous release of GABA (+44%), Asp (+50%) and Glu (+70%) in SHR, but not WKY; this effect was prevented by yohimbine (1 μM). These data, together with previous findings, support the presence of facilitory α2-adrenergic receptors on nerve terminals of GABAergic, glutamatergic and aspartatergic neurons in the rostral ventral medulla. These findings also suggest the existence of another inhibitory transmitter that may mediate the actions of clonidine to decrease sympathetic outflow from the RVL.

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