Thursday, June 28, 2018

Differential Activation of Adrenal, Renal, and Lumbar Sympathetic Nerves Following Stimulation of the Rostral Ventrolateral Medulla of the Rat

By: Patrick J. Mueller, Nicholas A. Mischel, and Tadeusz J. Scislo

The RVLM is involved in resting and reflex control of sympathetic activity and blood pressure. The RVLM employs a variety of mechanisms of control, both direct and indirect, to carry out its functions: for example, blood pressure and sympathetic may be controlled directly by vasoconstriction initiated by the RVLM. However, they may also be controlled indirectly through activation of the adrenal and renal nerves. Activating the adrenal nerve stimulates the release of epinephrine, resulting in an increase in cardiac rate and contractility, as well as skeletal muscle vasodilation. Activation of the renal nerve influences renal absorption, renin release, and mediates renal vasoconstriction, thereby controlling blood pressure through manipulation of blood volume. This raises the question: does activation of the RVLM result in differing patterns of nerve activity in the adrenal, renal, and lumbar nerves?

To test this, microinjections of glutamate were performed in the RVLM of the rats. The rats were anesthetized, and nerve activity was recorded simultaneously in all three nerves: renal, adrenal, and lumbar. It was assumed that nerve activity was at its baseline prior to activation; under this assumption, nerve activity was compared as a percent increase in activity in each nerve. Similar studies in cats have previously shown differential and selective nerve activation patterns after activation of the RVLM. This study is the first to observe such patterns in rats.  The authors contribute this to the proportionally smaller size of the rat as compared to the cat and the minute changes in volume and location that produce an effect. Specifically, changes in nerve activity were observed only when the position was shifted by 100–200 μm or when volume was increased by 15 nl. 

Four factors were tested, each leading to results that demonstrate differential and selective activation patterns: concentration of glutamate, volume of glutamate, decreasing mean arterial pressure, and blocking GABAA receptors. 

Concentration:
All nerve activity increased as concentration of glutamate increased.
Adrenal nerves (Pre- ASNA) were the most sensitive to changes in glutamate concentration; therefore, adrenal nerve activation increased by the greatest percentage in comparison to both renal and lumbar nerves.
Renal nerve (RSNA) activation also increased significantly in comparison to Lumbar nerve (LSNA) activation.

Volume:
Pre-ASNA and RSNA increased when volume increased.
LSNA did not change in response to volume. 
Pre-ASNA and RSNA also increased by a greater percentage than LSNA, just in response to the presence of glutamate. 

Decreasing Mean Arterial Pressure (MAP):
Sodium nitroprusside was used to decrease MAP
Pre-ASNA increased significantly compared to LSNA
No significant increase in RSNA compared to pre-ASNA or LSNA

Blocking GABAA Receptors:
Receptors were blocked with bicuculline 
Pre-ASNA and RSNA both increased significantly compared to LSNA
Bicuculline (blocking GABAA Receptors) is 3 to 4 times more effective at increasing nerve activity in all three nerves as sodium nitroprusside (decreasing MAP)

This study is important because determining differential and selective patterns of nerve activity can help "define the contribution of different sympathetic nerves and CNS sites to a given physiological or pathophysiological process."

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