Brain natriuretic peptide-mediated changes in the extracellullar neurotransmitter turnover in the rostral ventrolateral medulla

By: B.R. Dev, M. Nandakumaran, L. Philip, S.J. John. Published in the journal Neuroscience. 

 

Brain natriuretic peptide (BNP) is a hormone secreted by the ventricles of the heart in response to excessive stretching. It is associated with regulation of CV functions, BP, and HR. Increased plasma BNP concentrations have been found in people with CV dysfunctions such as congestive heart failure, hypertension, acute myocardial infarction, etc. Interestingly, other studies have shown that when BP is injected into rats, it only affects HR and BP in hypertension-model rats and not in normotensive-model rats. 

 

The purpose of this study was to observe changes in CV functions (MAP and HR) and in extracellular concentrations of certain neurotransmitters in the RVLM following introduction of BNP. This was accomplished in two ways in this study. The first method involved the use of microinjections. BNP was injected directly into the RVLM at different concentrations of BNP – 2,4,20, & 40 pmol. Changes in HR and MAP were observed throughout the experiment. The study found an overall dose-dependent decrease in HR and MAP following injection of BNP. The microinjections were later confirmed with histology techniques similar to the ones our lab is using.  

 

The second part of the study incorporated microdialysis. Microdialysis is a method by which a solution is slowly perfused through a tissue. As the solution enters the tissue, it may cause changes in the chemical concentrations inside and outside of the cell. These chemicals will diffuse across the membrane of the cell and will be collected in order to analyze. 

 

The BNP solution was perfused into the RVLM over an extended period of time (the full experiment, including use of a control perfusion solution, lasted 7h). The perfusate was collected and analyzed using a high-pressure liquid chromatography machine which separates chemicals in a column based on their weight. The study found a decrease in levels of norepinephrine and epinephrine, as well as an increase in 5-hydroxyindoleacetic acid (5-HIAA, a marker for serotonin). There was no significant change in concentrations of DOPAC (a marker for dopamine).  

 

Some questions I have that are inspired by this study: What are the mechanisms by which BNP causes a change in MAP and HR? Does it cause a change in receptor sites for GABA and glutamate, similar to what we may have noticed? Will a previously sedentary individual who begins to exercise see an increase or decrease in BNP?    

 

-- S. Kulkarni