Exercise Training Lowers the Enhanced Tonically Active Glutamatergic Input to the Rostral Ventrolateral Medulla in Hypertensive Rats

The authors tested how low intensity exercise affects the glutamatergic input to the RVLM in spontaneously hypertenive rats. They used WKY and SHR and trained them in treadmill for a period of 12 weeks. Citrate synthase concentration was measured as a measure of exercise training efficacy.  Microinjections were performed in the RVLM to study the changes in BP, HR and RSNA. Blood pressure for the time course experiment were performed using tail-cuff method. Western blotting was performed in RVLM punches to detect the changes in protein levels of vesicular glutamate transporter 2 (vGLUT2). High-performance liquid chromatography (HPLC) was used to measure the glutamate concentration. Data was analysed by a two-way ANOVA followed by post hoc with Student Newman-Keuls. Exercise training decreased the baseline BP and RSNA in SHRs. Execrise training attenuated the decrease in BP, HR and RSNA evoked by blockade of glutamate receptors in the RVLM of SHRs. Exercise training in the SHRs decreased the concentration of glutamate and protein expression of vGLUT2. The overall conclusion is that exercise training lowers the tonically active gluamatergic input in the RVLM of SHRs.

-Madhan

PACAP causes PAC1/VPAC2 receptor mediated hypertension and sympathoexcitation in normal and hypertensive rats.

Am J Physiol Heart Circ Physiol. 2012 Oct 1;303(7):H910-7. 
Farnham MM, Lung MS, Tallapragada VJ, Pilowsky PM.

"Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuropeptide that plays and important role in hypertension and stress responses". 

The authors proposed an idea that PACAP acts as a sympathoexcitatory agent in the RVLM of normotensive and hypertensive rats. The had 3 specific aims for the experiment and tested them using different mechanisms as in described in the above illustration. The major findings of this study is that injection of PACAP in the RVLM caused an increase in splanchnic SNA, heart rate and MAP in SHR, WKY and SD rats. Pretreatment with PAC1/VPAC2 receptor antagonist PACAP (6-38) attenuated this response but did not produce any changes when injected alone suggesting that PACAP receptors are not tonically active. PACAP (6-38)  in the RVLM produced no changes in sSNA or MAP in the SHR suggesting they may not play a role in maintaining hypertension in SHR.

-Madhan

Oxidative stress in the rostral ventrolateral medulla modulates excitatory and inhibitory inputs in spontaneously hypertensive rats

J Hypertens. 2012 Jan;30(1):97-106.  

Nishihara M, Hirooka Y, Matsukawa R, Kishi T, Sunagawa K.

This study aims at answering 3 important questions.

1. Determine whether chronic oxidative stress in the RVLM alters synaptic transmission through glutamatergic inputs.

2. Determine whether chronic oxidative stress in the RVLM alters synaptic transmission through GABA-ergic inputs.

3.  Determine whether chronic oxidative stress in the RVLM alters synaptic transmission through excitatory inputs from the PVN.

Adenoviral vectors encoding MnSOD was transferred into the RVLM of male SHRs and WKYs. Microinjection studies using Kynurenic acid (Glutamate receptor antagonist) and Bicuculline (GABA receptor antagonist) showed that reactive oxygen species (ROS) in the RVLM enhanced the excitatory glutamatergic inputs and reduced the GABAergic inputs to the RVLM neurons in SHRs. In addition, activation of the PVN neurons enhanced the pressor and sympathoexcitation through ROS in the RVLM. These findings suggest that ROS in the RVLM increases glutamatergic excitatory inputs and decreases GABAergic inputs in SHRs.

Madhan