Blunted sympathoinhibitory responses in obesity-related hypertension are due to aberrant central but not peripheral signalling mechanisms

Jackie M. Y. How, Suhail A. Wardak, Shaik I. Ameer, Rachel A. Davey, Daniela M. Sartor
J Physiol. 2014 Apr 1;592(7):1705-20.


While our lab studies the effect of sedentary conditions, other labs look at other aspects of an unhealthy lifestyle. In this study, they examined the effect of a medium high fat diet vs a low fat diet. The rats on the medium high fat diet that gained the most weight were dubbed obesity prone (OP) while the ones that didn't gain as much were dubbed obesity resistant (OR). Their goal was to look for changes in central mechanisms and/or peripheral mechanisms of controlling sympathetic nerve activity. To do this, they looked at the activity of individual RVLM neurons, in vivo, and tested two sympathoinhibitory stimuli - the baroreflex (via aortic occlusion) and infusion of cholecystokinin (CCK, acts at vagal afferents) upstream from the coeliac artery.
RVLM neurons in OP rats showed a poor synchronicity with the pulse pressure, and their CCK-induced inhibition was pretty much abolished compared to OR  and control rats fed low fat diets - so much so that some neurons were actually slightly excited by it. The also showed a decreased inhibition caused by increases in blood pressure. The pressure needed to attain 20% reduction in firing frequency was increase both in terms of percent change and absolute pressure. Only 2 of 8 neurons from OP rats could even be inhibited beyond 20%, compared to 10 of 11 neurons in the other groups being inhibited 20-100%. Despite these changes in response to stimuli, there was no significant difference in baseline firing frequency, though OP rats were slightly higher.
They also looked at FOS immunoreactivity in the NTS and CVLM, finding that the OP rats had fewer FOS-IR in the NTS after CCK administration compared to saline controls, but in the CVLM, OP rats had fewer FOS-IR cells compared to both OR and controls.
To show that the diet-induced changes were central rather then peripheral, they looked at subdiaphragmatic nerve discharge during CCK infusion and found no difference between groups.
I liked this paper because it adds to the growing body of knowledge that says the brain does stuff. Many people still think that changes in blood pressure are due to peripheral effects rather than central, but this study shows there are strong changes in the RVLM due to differences in something simple as your diet. I guess the only other question is that if the presympathetic nerves are changing, what good does that do if it's not affecting sympathetic nerve activity (in that particular nerve)? -DJH