A five-parameter logistic equation for investigating asymmetry of curvature in baroreflex studies.

Ricketts JH, Head GA.
Am J Physiol. 1999 Aug;277(2 Pt 2):R441-54.

   This paper started off with the first two pages as a review of different techniques which had previously been used to mathematically describe baroreflex curves measuring arterial pressure against nerve activity and heart rate. It then went on to describe a new method, a 5-parameter equation, that was predicted to be able to account for asymmetry sometimes seen in baroreflex curves. The argument in favor of this new method was that it would be able to fit a curve better when the curve showed asymmetry between upper and lower limits, or differences in slope on either side of the midpoint. If no such asymmetry existed, the 5th parameter was averaged out and the formula was able to approximate the curve the same way a traditional 4-parameter equation would.

   The paper then went on to analyze pre-existing baroreflex data of MAP vs heart rate and renal nerve sympathetic activity in rabbits and dogs via 4- and 5- parameter curves - in both cases, they tested by forcing the curves to fit to the resting points and tested again without forcing them. They found that when there was an asymmetry in the curves of some subjects, the 5-parameter equation could account for it, though for the most part the 5-parameter method did not report values that were significantly different than the 4-parameter method. The biggest changes seemed to be caused by forcing the curve through the resting point, and according to this paper, doing that seems like a questionable technique. The paper did make a good point that even though this technique may not result in significantly different results over the 4-parameter technique in most cases, in cases where asymmetry is present, it will yield a more accurate result - and if you need it for one parameter, you should use the same technique for all parameters within a study. I think that's a pretty fair argument. -DH

Physical Activity and Cardiorespiratory Fitness Are Beneficial for White Matter in Low-Fit Older Adults

Agnieszka Zofia Burzynska, Laura Chaddock-Heyman, Michelle W. Voss, Chelsea N. Wong, Neha P. Gothe, Erin A. Olson, Anya Knecht, Andrew Lewis, Jim M. Monti, Gillian E. Cooke, Thomas R. Wojcicki, Jason Fanning, Hyondo David Chung, Elisabeth Awick, Edward McAuley, and Arthur F. Kramer

PLoS One. 2014; 9(9): e107413.

Our lab studies effects of sedentary vs physical activity on the brain and have shown an active lifestyle to be overall beneficial to cardiovascular health. I found this paper exciting because it looks at not only how an active lifestyle and good cardiovascular health can have positive effects on white matter later in life but also the neural correlates for these relationships. Using 88 healthy low-fit adults they examined the relationship between cardiorespiratoy fitness (CRF) with three different levels of physical activity (PA) and how it affected the levels of white matter (WM). Adults used for this study were between the ages of 60-79 years old, had no history of stroke or neurological illness, and had similar scores thresholds many other test. Participants PA was monitored for a week with a accelerometer worn on the hip and measurements collected placed them in one of the three levels of PA: sedentary behavior, light PA, and moderate to vigorous PA (MV-PA). T2 weighted MRI images were used to examine the integrity of WM and presence of white matter hyperintensities (WMH); lesions that appear in WM during old age that damage WM integrity. Age-related degeneration of WM micro-structures can be captured as decreased fractional anisotropy (FA) measured with diffusion tensor imaging (DTI). The study concluded that higher levels of MV-PA were linked to lower WMH volume, PA and CRF are related but not equivalent in their relationships with WM health in aging, and PA is associated with WM health in aging in an intensity- and region-specific manner. 

It’s interesting to look at the additional effects an active lifestyle can have on the body past the cardiovascular level. This paper shows it’s never too late to start doing any level of PA and that its has many of its benefits are still unknown to us. 

Zachery

Nucleus ambiguus inhibits activity of cardiovascular units in RVLM.

McKitrick DJ, Calaresu FR.
Brain Res. 1996 Dec 2;742(1-2):203-10.

   In our lab we tend to think mostly of the activity in the RVLM as increasing sympathetic nerve activity because of signals coming from the baroreceptors through the NTS and the CVLM. This paper examines the interaction between the sympathetic and parasympathetic nerve activity (PSNA) by injecting glutamate into the nucleus ambiguus (NA, excited by the NTS to activate PSNA) and measuring the effect on the activity of neurons in the RVLM of urethane-anesthetized rats. Because activating the NA would cause a direct drop in cardiac output which would also activate the RVLM, they used atropine to block the inhibitory effect of the NA on the heart.
   The cells they examined fired at about 7Hz at resting. They were not examined for latency or conduction velocity via antidromic activation because they considered the cardiac rhythmicity and barosensitivity to be indicitive of presympathetic neurons, but they mentioned that the possibility exists that some of them may not have been. Of the neurons they tested, 24 of 36 decreased activity after microinjection of glutamate into the nucleus ambiguus (NA), hinting at an inhibitory connection between the two structures. Injection of the inhibitory amino acid, glycine, into the NA, did not cause an increse in firing frequency, but did enhance the cardiac rhythmicity. They discuss that the data suggests that the NA might have a a direct effect on the RVLM, but they suggest that there might be other pathways in play, such as a direct connection from the NTS to the RVLM, that they did not eliminate in their preparation. So they can't conclude in this paper that that the NA directly connects to the RVLM, but it hints at a possible mechanism for a cool effect. -DJH

Sympathetic activity and blood pressure are tightly coupled at 0.4 Hz in conscious rats

David R. Brown, Laura V. Brown, Abhijit Patwardham, and David C. Randall

Am J Physiol. 1994 Nov;267(5 Pt 2):R1378-84

This study looked at the interactions of sympathetic nerve activity (SNA), blood pressure (BP), and heart rate (HR) at the 0.4Hz frequency. As where the studies in our lab are looking at the changes of signal coherence of active and sedentary conditions is study look at the coherence in rats while they rested in a cloth sock, roamed freely in there home cage, and after anesthesia. The data was obtained in a similar method that our lab uses. Electrodes were attached to the renal sympathetic nerve to measure SNA, while catheters were placed in the left jugular and aorta to administer drugs. All the data for each rat was collected over a 9.56 min period. The data showed in conscious rats that SNA frequency peaked at 0.4Hz while the BP and HR were at lower frequency's. Although they did note that the BP did display a some higher 0.4Hz frequency not seen in HR. The coherence of the SNA - BP was at its highest at the 0.4Hz and declined as the frequency got lower. Anesthesia did not change the coherence of SNA - BP. This study shows that SNA and BP are coupled at the 0.4Hz frequency and suggest that maybe BP reflects SNA. I agree with these results because SNA results from output of rostral ventral lateral medulla (RVLM) unit neurons which are influenced by BP.

-Zachery

Ventrolateral medulla in spontaneously hypertensive rats and the role of angiotensin 2

In this week’s blog, I reviewed a paper that studied the role of Angiotensin II in the ventrolateral medulla (VLM) in spontaneously hypertensive rats (SHR) and its contributions to cardiovascular regulation. Initially, Muratani et al, examined the VLM by microinjection of Angiotensin II antagonist into the rostral or ventral portion of the VLM. The antagonist caused a depressive effects and bradycardia in the RVLM, conversely, causing stimulating effects and tachycardia in the CVLM. Ultimately, blood pressure increased in SHR compared to the control group of normotensive rats. A group of 32 male rats between 14-16 week old were used in this study. Animals were anesthetized using urethan before injection. The results of this experiment indicated microinjections of Angiotensin II antagonist into the CVLM increased blood pressure and heart rate in SHR compared to normotensive rats. On the contrary, Angiontensin II antagonist injection into the RVLM produced a depressive response ultimately decreasing mean arterial pressure and heart rate. Therefore, angiontensin II receptor blockage in the VLM imply that angiotensin II has a tonic effect on the neural activity of the RVLM and CVLM of SHR. Furthermore, the results of this study show that brain Angiotensin II contribute to the continual regulation neural activity of the VLM and its regulation of the blood pressure.

This was an older paper that I read on angiotensin II and though it doesn’t directly relate to what I am currently working on, it did focus on the VLM and how different aspects can effect its regulation of blood pressure. Furthermore, since CV is the leading cause of death, it shows that continual research still must be conducted on this brain region to figure alternative ways to regulate on blood pressure and ultimately reduce the amount of deaths from CV.

Dean

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

Attenuated baroreflex control of sympathetic nerve activity after cardiovascular deconditioning in rats

J. A. Moffitt, C. M. Foley, J. C. Schadt, M. H. Laughlin, E. M. Hasser
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology Published 1 May 1998 Vol. 274 no. 5, R1397-R1405

  This study used male rats to measure the effect of 14 days of hindlimb unloading (HU) on mean arterial pressure (MAP) vs heart rate(HR) , renal sympathetic nerve activity (RSNA), and lumbar sympathetic nerve activity (LSNA - controls hindlimb skeletal muscle) by intravenously infusing PE and SNP. This gave them the ability to construct baroreflex curves covering roughly 45-170mmHg MAP for each animal. The curve parameters for each animal were then averaged to make group curves and compared between HU and control rats.
  Similar to the other study on HU I blogged (which was done by some of the same people, after this study), HU rats had decreased body weight and soleus muscle mass. They found that HU also caused a resting tachychardia. However,  there were no significant differences in resting MAP, or maximum/minimum HR.
  LSNA was greatly attenuated in the HU group. Where control rats showed a LSNA increase to 350% of baseline at MAP of ~40mmHg, HU rats were only able to increase LSNA to 200%. the midpoint MAP was not different between groups, and the minimum LSNA at high MAP for both groups was at ~0%. This produced a significant reduction in gain as well. When viewed as a percent of maximal nerve activity, HU rats showed a significantly higher resting LSNA than controls, suggesting a reduction in response range rather than a reduction in absolute nerve activity.
  The results of looking at the RSNA were pretty similar to those of the LSNA; reduced maximum as a % of baseline, reduced gain, and a higher resting RSNA (as a percentage of the maximum). However, minimum RSNA was significantly lower in HU rats, where it wasn't in terms of LSNA.
  The take-home message here is that lack of regular exercise, or deconditioning, causes increases in resting SNA at the level of the kidney and skeletal muscle, and that leads to a reduction in the reserve SNA needed to meet the demands of decreases in MAP. -DJH