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

Exercise training causes sympathoinhibition through antioxidant effect in the rostral ventrolateral medulla of hypertensive rats

Clin Exp Hypertens. 2012;34(4):278-83.
Kishi T, Hirooka Y, Katsuki M, Ogawa K, Shinohara K, Isegawa K, Sunagawa K.

The authors were interested to know whether exercise training affects sympathetic nerve activity through central mechanisms in stroke-prone spontaneously hypertensive rats (SPSHR). They performed a series of experiments to determine the role of oxidative stress and angiotensin II in this pathway. First, they implanted radio-telemetry system to measure mean arterial pressure and heart rate in both SHRSP and Wistar-Kyoto (WKY) rats. The animals were seperated into 4 groups exercise trained (Treadmill) and non exercise trained for 28 days. After 28 days, urinary norepinephrine was measured as an indicator of sympathetic nerve activity. They measured conscious baroreflex sensitivity by spontaneous sequence method. Thiobarbituric acid-reactive substances were measured from RVLM punches as an indicator of oxidative stress. Tempol, a superoxide dismutase mimetic and angiotensin II were microinjected into the RVLM to determine the pathway. The overall findings are that exercise training in SHRSP caused sympathoinhibition and improved baroreflex sensitivity and reduced oxidative stress through blocked AT1R in the RVLM.

-Madhan

Time course of sympathoadrenal adaptation to endurance exercise in man

Today's blog post is on a paper published before we were born. Well, most of us anyway :-P

One of the first documented physiological effects of endurance exercise training was that trained subjects exhibited lower heart rates during exercise as compared to untrained. In this study, the authors wanted to determine the time course of development of this phenomenon as well as the relationship to whole body sympathetic nervous system activity. They took six normal dudes and put them on a seven week exercise training program involving both cycling and running. The intensity of training was increased at week four of the program. At one week intervals while subjects were training, they measured heart rate and plasma levels of catecholamines and lactate during isolated acute bouts of exercise. As expected, heart rate during acute bouts of exercise decreased over time, with further reduction when intensity was increased. Interestingly, plasma catecholamines decreased over time as well, but were not further decreased when training intensity was increased. The authors suggest that the decrease in heart rate during the first phase of training is mediated by decreased sympathetic action on the heart. The second phase of training however, produces effects on heart rate independent of the SNS, maybe through increased parasympathetic tone alone.

This and other exercise training studies performed around that time were among the first to establish the effect that chronic exercise has on autonomic control of the cardiovascular system. Without it, we would all be just running blots and doing PCR instead of cool rat experiments.

Exercise Training Restores Baroreflex Sensitivity in Never-Treated Hypertensive Patients

Laterza MC, de Matos LD, Trombetta IC, Braga AM, Roveda F, Alves MJ, Krieger EM, Negrão CE, Rondon MU. Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.Hypertension. 2007 Jun;49(6):1298-306. Epub 2007 Apr 16.


As we have already established, the baroreflex is an important mechanism in cardiovascular control, and exercise is a good way to deal with the hypertension. There is a possibility that arterial baroreflex sensitivity is decreased in individuals who suffer from some cardiovascular diseases, such as hypertension. Based on this possibility, the researchers in this study wanted to find if there was a decreased baroreflex response upon muscle sympathetic nerve activity (MSNA) and blood pressure (BP) and whether these two parameters were related in their changes in response to the exercise.


Using 20 hypertensive individuals who have never been treated for that condition before, as well as 10 normotensive individuals as a control, they made two subgroups of exercise-trained and non-exercised trained individuals. The MSNA was monitored by microneurography, and the BP was monitored both by sphygmomanometer and by a finger photoplethysmography device. Arterial baroreflex responsiveness was measured by infusion of either phenylephrine or sodium nitroprusside into the antecubital vein while monitoring drug effects upon mean BP, MSNA, and heart rate.


In the hypertensive individuals, their BP was significantly higher than in the normotensive individuals, and their MSNA had a higher burst frequency and burst incidence than the normotensive individuals. Baroreflex control of the BP was significantly lower in the hypertensive individuals. At the conclusion of the experiment, the baroreflex control of the exercise trained individuals was more on par with the baroreflex control of the normotensive individuals. Also, the changes in MSNA and changes in BP were significantly correlated in the exercise-trained and non-trained individuals.


Therefore, baroreflex control of MSNA was shown, by this study, to be decreased in hypertensive individuals, and that exercise would produce control that is similar to the level found in normotensive individuals. Also, the study showed a relationship between MSNA activity and BP, but does not establish how they are related.