Plasticity of GABAergic control of hypothalamic presympathetic neurons in hypertension.
Increased sympathetic outflow contributes to the pathogenesis of hypertension. However, the mechanisms of increased sympathetic drive in hypertension remain unclear. We examined the tonic GABAergic inhibition in control of the excitability of paraventricular (PVN) presympathetic neurons in spontaneously hypertensive rats (SHR) and normotensive controls, including Sprague-Dawley (SD) and Wistar-Kyoto (WKY) rats. Whole cell patch-clamp recordings were performed on retrogradely labeled PVN neurons projecting to the rostral ventrolateral medulla (RVLM) in brain slices. The basal firing rate of PVN neurons was significantly decreased in 13-wk-old SD and WKY rats but increased in 13-wk-old SHR, compared with their respective 6-wk-old controls. The GABA(A) antagonist bicuculline consistently increased the firing of PVN neurons in normotensive controls. Surprisingly, bicuculline either decreased the firing or had no effect in 59.3% of labeled cells in 13-wk-old SHR. In contrast, the GABA(B) antagonist CGP-55845 had no effect on the firing of PVN neurons in normotensive controls but significantly increased the firing of 75% of cells studied in 13-wk-old SHR. Furthermore, the evoked GABA(A) current decreased significantly in labeled PVN neurons of 13-wk-old SHR compared with that in normotensive controls. Both the frequency and amplitude of GABAergic spontaneously inhibitory postsynaptic currents were also reduced in 13-wk-old SHR. This study demonstrates an unexpected functional change in GABA(A) and GABA(B) receptors in regulation of the firing activity of PVN-RVLM neurons in SHR. This change in GABA(A) receptor function and GABAergic inputs to PVN output neurons may contribute to increased sympathetic outflow in hypertension.
Li
De-Pei
DP
Department of Anesthesiology H187, Pennsylvania State University College of Medicine, 500 University Dr., Hershey, Pennsylvania 17033, USA.
Pan
Hui-Lin
HL
D000200:Action Potentials; D000818:Animals; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology; D009473:Neuronal Plasticity; D010286:Paraventricular Hypothalamic Nucleus / Q000503:physiopathology*; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid