Key result
Renovascular hypertension in rats increased the density of GAD67ir and VGLUT2ir boutons in PVN-RVLM neurons (P<0.001), resulting in a net predominance of excitatory over inhibitory inputs.
Anatomical remodeling of GABA and glutamate afferent inputs in the PVN leads to a net predominance of excitatory inputs, potentially driving enhanced neurohumoral activity in renovascular hypertension.
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May drive sympathetic overactivity in renovascular hypertension; hypothesis-generating for human neurogenic mechanisms.
Altered hypothalamic synaptic function contributes to exacerbated neurohumoral drive in hypertension. Using immunohistochemistry and tract‐tracing techniques, we determined if remodeling of afferent GABAergic and glutamatergic inputs in PVN‐RVLM neurons contributes to the imbalanced excitatory/inhibitory function observed in renovascular hypertensive rats (RVH). The density of GAD67ir and VGLUT2ir boutons increased in PVN‐RVLM neurons from RVH rats (P< 0.001). Despite this concomitant increase, time‐dependent and compartment‐specific differences in their reorganization resulted in an altered balance of excitatory/inhibitory inputs. In SHAM and early stage RVH rats (3 weeks), cell body VGLUT2ir predominated over GAD67ir (P< 0.001); no differences were observed in proximal dendrites. Conversely, in late‐stage RVH rats (6 weeks), the somatic VGLUT2/GAD67 predominance diminished (P>0.5), while this relationship in proximal dendrites increased (P< 0.05). Our results support that anatomical remodeling of GABA and glutamate afferent inputs in the PVN, resulting in a net predominance of excitatory over inhibitory inputs, may contribute as an underlying mechanism to enhanced neurohumoral drive in renovascular hypertension. This work was supported by NIH HL090948‐01 to Stern JE and CAPES BEX0325/03‐1 (Brazil).
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Biancardi et al. (2009) studied Renovascular hypertension. Renovascular hypertension vs. SHAM was evaluated on Density of GAD67ir and VGLUT2ir boutons in PVN-RVLM neurons (p=< 0.001). Renovascular hypertension in rats increased the density of GAD67ir and VGLUT2ir boutons in PVN-RVLM neurons (P<0.001), resulting in a net predominance of excitatory over inhibitory inputs.
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