Repeated Mandibular Extension in Rat: A Procedure to Modulate the Cerebral Arteriolar Tone

Abstract

Previous data have shown both in the rat and in the human that a single mandibular extension lasting 10 min induces a significant important and prolonged reduction in blood pressure and heart rate, affecting also rat pial microcirculation by the release of endothelial factors. In the present work, we assessed whether repeated mandibular extension could further prolong these effects. We performed two mandibular extensions, the second mandibular extension being applied 10 min after the first one. The second mandibular extension produced a reduction in blood pressure and heart rate for at least 240 min. As in the case of a single mandibular extension, pial arterioles dilated persisting up to 140 min after the second extension. Spectral analysis on 30 min recordings under baseline conditions and after repetitive mandibular extensions showed that the pial arterioles dilation was associated with rhythmic diameter changes sustained by an increase in the frequency components related to endothelial, neurogenic, and myogenic activity while a single mandibular extension caused, conversely, an increase only in the endothelial activity. In conclusion, repetitive mandibular extension prolonged the effects of a single mandibular extension on blood pressure, heart rate and vasodilation and induced a modulation of different frequency components responsible of the pial arteriolar tone, in particular increasing the endothelial activity.

Pain Control by Proprioceptive and Exteroceptive Stimulation at the Trigeminal Level

“…Another possibility is that the effect is mediated by nitric oxide (NO). Previous studies have demonstrated that a mandibular extension very similar to that applied in our subjects, was able to substantially lower the systemic blood pressure in humans, and lead to an increase in the NO plasma levels in the rat ( Brunelli et al, 2012 ; Lapi et al, 2013 , 2014 , 2016 , 2017 ; Del Seppia et al, 2016 , 2017 ). Notably, NO has been implicated in pain transmission ( Rosenthal et al, 2015 ), and in some cases NO donors have been shown to produce antinociceptive effects, while NO synthase inhibitors lead to pain ( Yeo, 2002 ; da Silva et al, 2008 ; Fan et al, 2009 ).…”

Renin-Angiotensin System Responds to Prolonged Hypotensive Effect Induced by Mandibular Extension in Spontaneously Hypertensive Rats

“…In the present study we evaluated the effects of a repeated ME procedure on modulation of main physiological parameters (BP and HR) and of principal components of RAS in SHRs, focusing primarily on the response in cerebral cortex. Previous studies in normotensive rats, investigating arteriolar tone modifications, have shown that the stimulation of trigeminal nerve by ME procedure determines a prolonged hypotensive effect accompanied by initial rapid vasoconstriction, followed by a prolonged vasodilation y in the pial microcirculation ( Lapi et al, 2017 ). Furthermore, our studies on humans demonstrated that the submaximal mouth opening for a relatively brief time (10 min) was followed by a prolonged hypotensive and bradycardic effect on normotensive volunteers ( Del Seppia et al, 2016 , 2017 ).…”

“…It is known from the literature that SHR hypertensive phenotype in the brain is greatly sustained by an alteration of a balance in ACE/ACE2, and that AngII synthesis is favored with respect to Ang(1-7) generation ( Gowrisankar and Clark, 2016 ). Specifically, in our SHR model, two hypotensive ME procedures were performed, as previously described in normotensive rats ( Lapi et al, 2017 ). These results are in accordance with those obtained in normotensive rats in which a repeated stimulation induced a decline in BP by nearly 20 mmHg ( Lapi et al, 2017 ), and suggest that the hypotensive effect is even greater (about 28 mmHg, Figure 2B ) and more prolonged in hypertensive animals.…”

“…Specifically, in our SHR model, two hypotensive ME procedures were performed, as previously described in normotensive rats ( Lapi et al, 2017 ). These results are in accordance with those obtained in normotensive rats in which a repeated stimulation induced a decline in BP by nearly 20 mmHg ( Lapi et al, 2017 ), and suggest that the hypotensive effect is even greater (about 28 mmHg, Figure 2B ) and more prolonged in hypertensive animals. At molecular level, AT1R and ACE gene expression were significantly reduced only in parietal area while they did not change in frontal region.…”

“…To induce ME, was used a home-made U-shaped dilatator appropriately designed for rats and described previously ( Lapi et al, 2013 , 2017 ). All ME lasted for 10 min.…”