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

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.

Thyroid hormone deiodinases response in brain of spontaneausly hypertensive rats after hypotensive effects induced by mandibular extension

“…Our results confirm previous observations in SHR [17,18] showing a marked decrease in MBP and HR induced after two MEs and suggest, for the first time, a possible involvement of deiodinases in the compensative response to a hypotensive stimulus (ME) in rat brain cortex. So far, data available on deiodinases expression in the rodent brain are limited to observations in hyper-or hypo-thyroid conditions or in association with the brain maturation [15,26,27].…”

“…Rats underwent a double mandibular extension (ME) treatment, in order to induce a hypotensive response throughout the trigeminal nerve stimulation [17,18]. In general, the facial area presents many autonomic reflexes having trigeminal fibers as afferent branches.…”

Interaction between the Renin–Angiotensin System and Enteric Neurotransmission Contributes to Colonic Dysmotility in the TNBS-Induced Model of Colitis

“…RNA quantification and purity were measured spectrophotometrically at 260/280 in a plate reader (BioTek Synergy) adapted for 2 µL volume readings (Take3 adapter, BioTek, Winooski, VT, USA). Real-time polymerase chain reactions (qPCRs) were carried out applying SsoAdvanced™ Universal SYBR® Green Supermix (BioRad, Hercules, CA, USA) and run on a Bio-Rad CFX 96 thermalcycler using rat-specific primer pairs for the receptors AT 1 and AT 2 , shown in Table 3 [ 74 ]. Data was normalized to the expression of housekeeping genes Papbn, Hprt-1 and Hmbs, whose expression was altered by sex, using the delta-delta C t ( ΔΔ C t ) method [ 75 ].…”

Fetal Undernutrition Modifies Vascular RAS Balance Enhancing Oxidative Damage and Contributing to Remodeling

“…Gene amplification protocol started with 95 • C for 30 s, followed by 39 cycles at 95 • C for 15 s and 60 • C for 30 s. Each assay was performed in a triplicate with a negative control. The relative expression of the genes Renin, ACE, ACE2, AT1 receptor, AT2 receptor, Mas receptor and MrgD [70] were calculated using the 2−∆∆Ct method [71], normalized to the expression of three housekeeping genes: HPRT-1: hypoxanthine phosphoribosyltransferase I; Hmbs: Hydroxymethylbilane synthase; and Papbn-1: Polyadenylate-binding protein 1 [72].…”