Sympathoinhibitory pathway from caudal midline medulla to RVLM is independent of baroreceptor reflex pathway

J.R. Potas and R.A.L Dampney

The authors of this paper were interested in whether the caudal midline medulla was causing sympathoinhibitory effects in response to glutamate stimulation by either causing activation of CVLM neurons or direct inhibition of RVLM neurons. In order to iinvestigate this question they injected kynurenate into CVLM and looked at responses to glutamate stimulation of CMM. they found that the sympathoinhition caused by activation of CMM was not inhibited. Next they wanted to see if blockade of GABA receptors in the RVLM would blunt the response. So they blocked the left RVLM so they would not get profound drops in bp and SNA and then they injected bicuculline into the RVLM and looked at responses to CMM stimulation. They found that the response was significantly blunted.

Conclusion: The sympathoinhibitory effects of CMM on the cardiovascular system is not due to activation of CVLM neurons but due to another pathway that ultimately leads to inhibition of RVLM neurons.
-M.D.

Cardiovascular Effects Produced By Activation of GABA Receptors In The Rostral Ventrolateral Medulla of Conscious Rats

The major inhibitory neurotransmitter is GABA .As we already know anesthesia can potentiate the effects of GABA. In this article they looked at the role of GABA on GABA _A and GABA _B receptors in conscious animals. They used Wistar rats. They only looked at blood pressure and heart rate. Their finding suggest that the GABA _A receptor is the most important for mediating the inhibitory response under conscious conditions however , GABA _B receptor were not important for the transduction of inhibitory signals. This suggests that anesthesia might alter the GABA B receptor or even potentiate the effects of GABA binding to GABA _B receptors in anesthetized animals.

The ventrolateral medulla and sympathetic regulation of arterial pressure.

ANN M. SCHREIHOFER AND ALAN F. SVED.  The ventrolateral medulla and sympathetic regulation of arterial pressure. In: Central regulation of autonomic functions.  2^nd Edition. Eds: I.J. Llewellyn-Smith and A.J. Verberne Oxford University Press, Inc. New York, 2011.

So in honor of our guest from Australia I thought it was timely to provide a posting on one of the chapters from Ida's recent book that will likely be considered the bible on neural control for at least the next 5-10 years.  The particular chapter I chose is of course most relevant to our studies on the RVLM, although other chapters in this book are also important in terms of our understanding of brainstem control of arterial pressure.  In this chapter Ann Schreihofer and Alan Sved provide a nice overview of the history and development of what the current knowledge is on brainstem control of sympathetic outflow.  They do a great job in discussing the number of techniques used to examine the ventrolateral medulla in term of it's anatomy and physiology.  Several nice figures combine immunohistochemistry, histology, BP and SNA responses etc. to illustrate the relationship between the CVLM and the RVLM.  There is also some clarification on the confusion caused by the original nomenclature of the C1 cells and that while serving as a useful marker for barosensitive, bulbospinal neurons controlling SNA, use glutamate not epinephrine serves as the primary neurotransmitters of RVLM neurons.  A thorough discussion of the roles of the RVLM and CVLM is provided.   There is a section of the caudal pressor area which while interesting, seems to pale in comparison to the importance of the CVLM and RVLM.  Finally, the last two sections are devoted to differential control and the role of the VLM in hypertension.  Both nice summaries but also highlight the number of unaswered questions that remain to be answered, some of which are being addressed in our laboratory.  Overall this is a chapter that every student, postdoc and faculty working in the field needs to be well-versed in so if you haven't done so recently or already, I would suggest giving it a look soon.

Posted by Pat

Bioactive Compounds in Berries Can Reduce High Blood Pressure

Blog Post July 15, 2011

Bioactive Compounds in Berries Can Reduce High Blood Pressure

ScienceDaily (Jan. 15, 2011) — Eating blueberries can guard against high blood pressure, according to new research by the University of East Anglia (UEA) and Harvard University.

http://www.sciencedaily.com/releases/2011/01/110114155241.htm

Science Daily is a good website for stimulating potential “out of the box” topics which high school students can use in their research process. Articles can also be used as an ice-breaker for lecture and lab. 

According to Science Daily, this study is also published in the American Journal of Clinical Nutrition (could not locate). The article summarizes research completed at the University of East Anglia (UEA) and Harvard University.  The posting got me thinking about connecting the article’s findings with microinjections.

According to the article, 181,000 people were placed in cohorts for a 14 year study. At the start of the study, none of the participants had hypertension. The study found that the participants who consumed flavonoids  were less likely (8%) to be diagnosed with hypertension. Those who ate blueberries once a week were 10% less likely to become hypertensive. So what are flavonoids and how are they related to what we do in our lab?

After a quick search in PubMed (and asking Jessica and Nick), I learned that  GABA lowers blood pressure when injected into the RVLM of rats. I probably heard this response to GABA during the Thursday lab meetings, but it finally clicked for me today--light bulb moment! A PubMed search for  “GABA + Flavonoid”, provided me with information that there is a flavone-binding site in the GABA(A)-receptor. This receptor is a ligand-gated ion channel and it responds to the neurotransmitter gamma-aminobutyric acid. Since microinjected GABA lowers blood pressure when injected into the RVLM and if consumption of blue berries lowers the risk of developing hypertension by 10%. Could we connect the two into an experiment in our lab? 

The receptor for GABA is a flavone-binding site, so what would happen if we injected a flavonoid into the RVLM? Would it decrease the blood pressure? And, what is the specific molecular conversation here? Would the flavonoid enhance the function of the receptor, serving like a cofactor or coenzyme?  Is there a conformational change in the receptor in the presence of flavonoid?