Erick A. Bourassa, Kristen A. Stedenfeld, Alan F. Sved,
Robert C. Speth
Neurochemical Research Vol. 40, Issue 10 (October 2015)
The rostral ventrolateral medulla (RVLM) contains
bulbospinal neurons that mediate sympathetic tone. These bulbospinal neurons
are activated in two ways: baroreflex (drop in blood pressure) or by excitatory
inputs from the paraventricular nucleus of the hypothalamus (PVN). The
renin-angiotensin (RAS) system also plays a role in the regulation of peripheral
blood pressure. Data suggests that elevated activity of the brain-specific
renin-angiotensin system contributes to hypertension.
Within the RVLM there are two distinct types of neurons: C1
and non-C1. C1 Both C1 and non-C1 neurons are spinally projecting
(bulbospinal), but they differ in that C1 neurons contain the enzymes required
to synthesize epinephrine (tyrosine hydroxylase (TH) and phenylethanolamine
N-methyltransferase (PNMT)), while non-C1 neurons do not. However, non-C1
neurons still express vGlu2, suggesting that they are glutamatergic like the C1
neurons. Studies have shown that both groups of neurons are involved in
cardiovascular responses, but it is unknown whether the affects of angiotensin
II (Ang II) in the RVLM are due to activation of the C1 neurons, the non-C1
neurons, or both. In this study, the AT1 receptor (Ang II receptor in the RVLM)
is used to determine how active the C1s are versus the non-C1s in response to
Ang II.
To test this, rats were either injected with DSAP
(anti-dopamine-beta-hydroxylase-saporin) or MZAB (control) into one side of the
RVLM. The other side of the RVLM was left alone to provide something to compare
the experimental side of the RVLM to. The DSAP targets and destroys C1 neurons,
while the MZAB has no effect. The rats were then decapitated 3-4 weeks
post-injection and their brain was sectioned and stained for TH (indicative of
C1 neurons). The number of C1 neurons in the RVLM of each rat was determined by
examination of the processed brain tissue via light microscopy. The number of
AT1 receptors was also determined, but by a different technique called
quantitative angiotensin receptor autoradiography. It is important to note that
two comparisons were made to determine results: comparison between right and
left RVLM (contralateral) of the same rat to determine percent change, followed
by comparison of the determined percent change between experimental RVLM and
control RVLM of different rats.
DSAP produced a 57% depletion of C1 neurons, using the contralateral
RVLM comparison, when compared to the contralateral comparison of the control
MZAB injected RVLM. Also, the AT1 receptor binding was 10% lower in the
experimental group when using the contralateral comparison, and 19% lower in
the experimental group when comparing the binding between the DSAP and MZAB
groups, not comparing contralaterally. If C1 neurons contained most of the AT1
receptors, as was previously thought, then a 57% decrease in C1 neurons would
result in a similar decrease in the amount of AT1 receptors, but this was not
the case. These results suggest that the non-C1 neurons in the RVLM contain
most of the AT1 receptors.
The result of this study is significant to my work in the lab because it reminds us that while we focus on one role of the RVLM, it has other functions as well. It can be activated and inhibited by other pathways and it is important to remember that these other pathways may affect the results of our studies
- Ben Huber
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