Abstract
There is an ongoing interest in the renin-angiotensin system (RAS) contribution either to pathological mechanisms leading to hypertension (mainly regarding the ACE/AngII/AT1R axis), or, to RAS protective and pro-regenerative actions, primarily ascribed to the mediation of the AT2R and the MAS1 receptor. In the present study, we evaluated the modulation of gene expression and protein levels of “deleterious” (ACE/AngII/AT1R) and “protective” [ACE/AngII/AT2R and ACE2/Ang(1-7)/MAS1 arms] RAS components in parietal and frontal areas of cerebral cortex of spontaneously hypertensive rats (SHRs), after two periods of mandibular extensions (MEs). Blood pressure, BP and heart rate, HR were also measured. While no significant changes in BP and HR were present in the sham operated (SO) group, in rats after two MEs (2-ME rats), BP displayed a marked decrease (p < 0.001) at ME2, and remained then stably low for the subsequent observation period. In gene expression analysis, in SHRs undergoing two MEs, either in parietal or frontal cortex, we did not observe any significant variation of AT2R and ACE2 with respect to SO rats. In contrast, we observed a decrease in Mas1 gene expression in parietal area (p < 0.01) and an increase in frontal region (p < 0.01). AT1R and ACE gene expression was significantly higher in 2-ME rats than SO in parietal cortex (p < 0.05) but no difference was observed in the frontal area. Concerning protein levels, in parietal area, AT1R and AT2R did not change whereas MAS1 significantly decreased in 2-ME rats (p < 0.05). In frontal area, both AT1R and AT2R significantly decreased in 2-ME rats (p < 0.05), whereas MAS1 did not significantly change. Gene expression analysis in normotensive (NT) rats revealed the non-detectability of AT1R in both parietal and frontal zone. In parietal area, AT2R (p < 0.0001) and Mas1 (p < 0.01) were significantly decreased in 2-ME NT rats, when compared to SO, and ACE and ACE2 resulted not detectable whereas there was some expression of these genes after 2-ME procedure. In conclusion, our data in rat models indicated that a 2-ME procedure induced a hypotensive response and that a modulation of gene expression and protein levels of RAS components occurred in different cerebral cortex areas.
Highlights
The facial area is an important site of autonomic reflexes involving parasympathetic and sympathetic nervous systems in the human and these reflexes have trigeminal fibers as afferent branches
We have shown that two periods of mandibular extension (ME) in the normotensive rat prolongs the effects of a single ME on blood pressure (BP), heart rate (HR) and vasodilation, modulating the pial arteriolar tone by the increase of endothelial activity (Lapi et al, 2014)
We evaluated gene expression of renin-angiotensin system (RAS) components in a group of normotensive (NT) rats undergoing ME procedure, in order to verify that observations on spontaneous hypertensive rat (SHR) were effectively related to the hypertensive condition
Summary
The facial area is an important site of autonomic reflexes involving parasympathetic and sympathetic nervous systems in the human and these reflexes have trigeminal fibers as afferent branches. Stimulation of specific facial regions may induce reflex with certain important implications (Brunelli et al, 2012). In normotensive rats, this effect was abolished by bilateral peripheral trigeminal section, indicating a fundamental role of trigeminal nerve in the hypotensive ME-induced response (Lapi et al, 2013). We have shown that two periods of MEs in the normotensive rat prolongs the effects of a single ME on BP, heart rate (HR) and vasodilation, modulating the pial arteriolar tone by the increase of endothelial activity (Lapi et al, 2014). ME might represent a procedure useful in the control of the systemic BP and, of the organ perfusion, in particular of the brain and vasculature in cardiovascular diseases, such as hypertension
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