Patrick J. Mueller, Nicholas A. Mischel, Tadeusz J. Scislo.
American Journal of Physiology – Regulatory, Integrative and Comparative Physiology (2011)
The sympathetic nerves are part of the autonomic nervous system, which controls unconscious actions, and are important in the response to changes in blood pressure. The rostral ventrolateral medulla (RVLM) has been shown to direct sympathetic nerve activity (SNA) to cardiovascular targets and may have a role in the increased SNA of cardiovascular diseases. This study specifically looks at three areas of SNA: preganglionic adrenal SNA (ASNA), renal SNA (RSNA), and lumbar SNA (LSNA). The goal of this study is to determine how stimulating the RVLM effects the adrenal, renal, and lumbar sympathetic nerves individually.
This study used seventeen Sprague-Dawley rats and they were anesthetized with a mixture of alpha-chloralose and urethane. Microinjections into the RVLM were done by using a triple-barrel micropipette at a 90 degree angle. Dye was injected after the experiments were done to later identify the RVLM as the injection point. All rats were then killed using Fatal-Plus euthanasia solution.
Different concentrations of glutamate, which is the major excitatory neurotransmitter, were injected to observe responses in nerve activity, blood pressure, and heart rate. When the different concentrations were given in a fixed volume, the blood pressure was shown to be significantly increased and while there was a small increase in heart rate, it was not significant. The preganglionic ASNA was shown to significantly increase at each concentration of glutamate. The 10mM and the 100mM concentrations of glutamate did not produce a significant difference in RSNA, but they were significantly increased from the 1mM concentration change in nerve activity. LSNA was significantly increased after the 100mM glutamate injection when compared to the 1mM or 10 mM concentrations. The preganglionic ASNA was shown to exhibit significant increased activity as the concentrations were increased. Overall, the preganglionic ASNA activity exhibited the largest increase out of the three nerves.
The next test was to keep the concentration fixed but change the volume of glutamate. Volumes of 15, 30, 60, or 90 nl were injected into the RVLM and then changes in nerve activity, heart rate, and blood pressure were observed. While heart rate was shown to not significantly change, blood pressure significantly increased at a volume of 90 nl when compared to 15 nl. Nerve activity did increase, but not as large of an increase as when volume was fixed and concentration increased. When the volume was changed from 15 nl to 30 nl, the preganglionic ASNA was the only one to show a significant increase. At 60 nl the RSNA was significantly increased compared to the activity at 15 nl. Nerve activity at 90 nl of glutamate exhibited increases in both RSNA and preganglionic ASNA, but not LSNA. While there did seem to be a small increase in LSNA, it was not significant.
Another study compared nerve activity after given a dose of sodium nitroprusside (SNP) to the nerve activity after a bicuculline (Bic) injection. SNP lowers blood pressure to cause an increase in nerve activity, which attempts to counteract the dilating effects of SNP. Bic is a GABA receptor blocker which leads to a large increase in nerve activity. The increase in nerve activity cause by Bic was about four times greater than the increase in nerve acitivty caused by SNP lowering blood pressure. While all nerves exhibited an increased response, preganglionic ASNA had the largest increase in response to SNP and Bic.
In conclusion, all three nerves exhibited increased sympathetic nerve activity when the RVLM was stimulated, though preganglionic ASNA increased more RSNA and LSNA. When the RVLM inhibitor is blocked, the SNA increase is much higher that the natural increase during low blood pressure. What I found most interesting about this study was the difference in activation between the Bic and SNP injections. I had not realized how much greater the response would be if all GABA receptors are blocked. This data helps to reinforce that even if blood pressure is very low and nerve activity is increasing to respond, there are still inhibitory factors in play.
-Paul M
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