The Hypotensive and bradycardic effects of mouth opening: evidence in an animal model.

Objective Previous studies in normotensive anesthetized rats (Lapi Arch.Ital.Biol 151:11-23,2013) showed that peripheral stimulation of the trigeminal nerve induced by submaximal mouth opening (mandibular extension, ME) caused prolonged (at least 80min) bradycardia, hypotension and cerebral hemodynamic changes (pial arterioles showed a characteristic response pattern consisting in a significant constriction during ME followed by a dilatation for the entire remaining observation time). Design and method In this study we assessed the in vivo effects of ME on HR, MABP and pial microcirculation in hypertensive rats. Experiments were performed in male Wistar rats weighing 250-300g (n = 8). Hypertension was induced by intraperitoneal daily injection of dexamethasone (0.03mg/kg/day) for 10 days. ME was obtained by inserting an ad hoc developed retractor between the dental arches. HR and MABP were recorded by ECG and a catheter placed in the left femoral artery and measured by a computer-assisted system. Pial arterioles were observed through a closed cranial window implanted above the left parietal cortex and visualized by an in vivo fluorescence microscopy technique to assess vessel diameter changes before (baseline), during 10min ME and thereafter until 160min. Arteriolar diameters were measured with a computer-assisted method (MIP Image program, frame by frame). Results In sham-treated (no ME) hypertensive rats (n=3) HR, MABP and pial microcirculation did not change during whole observation period. Hypertensive rats subjected to ME (n=5) showed a significant decrease of HR and MABP. HR declined by 42bpm, (p<0.01) starting from 60 min after ME up to 160min, while MABP by 18mmHg (p<0.05) starting from 20min after ME up to 100min, compared with baseline. Pial arterioles exhibited a biphasic response: the arteriolar diameter decreased by 2.94&#956;m (p<0.05) during ME, afterwards it significantly increased by 3.46&#956;m (p<0.01) starting from 20min after ME; this vasodilatation lasted for the whole observation period. Conclusions Our results suggest that ME is able to exert profound and prolonged regulatory effects on systemic arterial blood pressure and pial arteriolar tone in hypertensive rats

Hypotensive and bradycardic effects of mouth opening: evidence in the human

Objective Previous studies in normotensive anesthetized rats (Lapi Arch.Ital.Biol 151:11-23,2013) showed that peripheral stimulation of the trigeminal nerve induced by submaximal mouth opening (mandibular extension, ME) caused prolonged (at least 80min) bradycardia, hypotension and cerebral hemodynamic changes (pial arterioles showed a characteristic response pattern consisting in a significant constriction during ME followed by a dilatation for the entire remaining observation time). Design and method In this study we assessed the in vivo effects of ME on HR, MABP and pial microcirculation in hypertensive rats. Experiments were performed in male Wistar rats weighing 250-300g (n = 8). Hypertension was induced by intraperitoneal daily injection of dexamethasone (0.03mg/kg/day) for 10 days. ME was obtained by inserting an ad hoc developed retractor between the dental arches. HR and MABP were recorded by ECG and a catheter placed in the left femoral artery and measured by a computer-assisted system. Pial arterioles were observed through a closed cranial window implanted above the left parietal cortex and visualized by an in vivo fluorescence microscopy technique to assess vessel diameter changes before (baseline), during 10min ME and thereafter until 160min. Arteriolar diameters were measured with a computer-assisted method (MIP Image program, frame by frame). Results In sham-treated (no ME) hypertensive rats (n=3) HR, MABP and pial microcirculation did not change during whole observation period. Hypertensive rats subjected to ME (n=5) showed a significant decrease of HR and MABP. HR declined by 42bpm, (p<0.01) starting from 60 min after ME up to 160min, while MABP by 18mmHg (p<0.05) starting from 20min after ME up to 100min, compared with baseline. Pial arterioles exhibited a biphasic response: the arteriolar diameter decreased by 2.94&#956;m (p<0.05) during ME, afterwards it significantly increased by 3.46&#956;m (p<0.01) starting from 20min after ME; this vasodilatation lasted for the whole observation period. Conclusions Our results suggest that ME is able to exert profound and prolonged regulatory effects on systemic arterial blood pressure and pial arteriolar tone in hypertensive rats

Repeated mandibular extension in rat: A procedure to modulate the cerebral arteriolar tone

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

Trigeminocardiac reflex by mandibular extension on rat pial microcirculation: Role of nitric oxide

In the present study we have extended our previous findings about the effects of 10 minutes of passive mandibular extension in anesthetized Wistar rats. By prolonging the observation time to 3 hours, we showed that 10 minutes mandibular extension caused a significant reduction of the mean arterial blood pressure and heart rate respect to baseline values, which persisted up to 160 minutes after mandibular extension. These effects were accompanied by a characteristic biphasic response of pial arterioles: during mandibular extension, pial arterioles constricted and after mandibular extension dilated for the whole observation period. Interestingly, the administration of the opioid receptor antagonist naloxone abolished the vasoconstriction observed during mandibular extension, while the administration of Nω-Nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, abolished the vasodilation observed after mandibular extension. Either drug did not affect the reduction of mean arterial blood pressure and heart rate induced by mandibular extension. By qRT-PCR, we also showed that neuronal nitric oxide synthase gene expression was significantly increased compared with baseline conditions during and after mandibular extension and endothelial nitric oxide synthase gene expression markedly increased at 2 hours after mandibular extension. Finally, western blotting detected a significant increase in neuronal and endothelial nitric oxide synthase protein expression. In conclusion mandibular extension caused complex effects on pial microcirculation involving opioid receptor activation and nitric oxide release by both neurons and endothelial vascular cells at different times

Early Hypertension Is Associated With Reduced Regional Cardiac Function, Insulin Resistance, Epicardial, and Visceral Fat

Mild-to-moderate hypertension is often associated with insulin resistance and visceral adiposity. Whether these metabolic abnormalities have an independent impact on regional cardiac function is not known. The goal of this study was to investigate the effects of increased blood pressure, insulin resistance, and ectopic fat accumulation on the changes in peak systolic circumferential strain. Thirty-five male subjects (age: 47±1 years; body mass index: 28.4±0.6 kg . m −2 ; mean±SEM) included 13 with normal blood pressure (BP: 113±5/67±2 mm Hg), 13 with prehypertension (BP: 130±1/76±2 mm Hg), and 9 newly diagnosed with essential hypertension (BP: 150±2/94±2 mm Hg) who underwent cardiac magnetic resonance tissue tagging (MRI) and MRI quantitation of abdominal visceral and epicardial fat. Glucose tolerance, on oral glucose tolerance test, and insulin resistance were assessed along with the serum lipid profile. All of the subjects had normal glucose tolerance, left- and right-ventricular volumes, and ejection fraction. Across the BP groups, left ventricular mass tended to increase, and circumferential shortening was progressively reduced at basal, midheart, and apical segments (on average, from −17.0±0.5% in normal blood pressure to −15.2±0.7% in prehypertension to −13.6±0.8% in those newly diagnosed with essential hypertension; P =0.004). Reduced circumferential strain was significantly associated with raised BP independent of age ( r =0.41; P =0.01) and with epicardial and visceral fat, serum triglycerides, and insulin resistance independent of age and BP. In conclusion, regional left ventricular function is already reduced at the early stages of hypertension despite the normal global cardiac function. Insulin resistance, dyslipidemia, and ectopic fat accumulation are associated with reduced regional systolic function

Pain threshold is reduced in depression.

Pain and depression may share common neurochemical substrates, therefore the study of pain sensation in depression might be valuable in the investigation of the pathophysiology of depression itself. In order to investigate the sensation of pain in depression, we measured pain threshold and sensory threshold by means of a dental tester, comparing a group of depressed patients with healthy volunteers. The results showed the presence of a higher sensory threshold and pain threshold in patients than in controls. This may be related to a hyperfunction of the opiate system, which in turn might be primary or secondary to a decreased modulatory function of other neurotransmitters, in particular of serotonin, whose abnormalities in depressive states are well-documented

The importance of knowing the timing within the menstrual cycle in non-menopausal hypertensive women in the diagnostic workup for primary aldosteronism

We read with interest the paper by Ahmed el al (1), which demonstrates the importance of knowing the timing within the menstrual cycle when a diagnostic test is done for primary aldosteronism in non-menopausal women, reporting greater percentages of positive fludrocortisone suppression tests in the luteal compared to the follicular phase. Interestingly, a positive fludrocortisone test in the luteal phase was less likely to predict subsequent positive adrenal vein sampling than in the follicular phase, suggesting a lesser diagnostic accuracy of the test in the luteal phase. In their paper, the Authors focused on a late step of the diagnostic workup for hyperaldosteronism, that generally consists of performing a confirmatory test (such as the fludrocortisone test) after an initial laboratory positive screening test by means of determination of plasma aldosterone and renin levels. As also mentioned by Ahmed et al, some years ago we provided evidence that the menstrual cycle may affect the diagnostic performance for primary aldosteronism even in the early laboratory screening phase in hypertensive female patients (2) in a way similar to that observed by Ahmed, i.e. a higher "positivity" for suspected hyperaldosteronism when the test was done in the same women in the luteal compared to the follicular phase. We also recently confirmed this finding in an extended series of patients (3) (Fig 1). This article is protected by copyright. All rights reserved

INDEXES OF PERCEIVED STRESS AND ANXIETY: AN OBSERVATIONAL STUDY IN NEWLY EVALUATED HYPERTENSIVE PATIENTS

Background: Chronic stress and anxiety are frequently associated with arterial hypertension (Greenage et al. Curr Atheroscler Rep, 2010) and related to sympathetic activation and hypothalamic, hypophyseal and adrenal activation. A link between plasma aldosterone and stress/anxiety has also been recently suggested both in animals and humans, particularly in women (Jezova and Hlavacova, Ann. N.Y.Acad.Sci, 2008). Objective: To investigate in hypertensive subjects the relationships between emotional stress and anxiety with endocrine or hemodynamic parameters as assessed in a routine diagnostic workup for arterial hypertension. Design and Methods: An observational study was started in day-hospital hypertensive patients (n = 74 up to date, 38M, 36F; mean age &#61503;SD 53 &#61503;14), including two questionnaires for self-perceived stress (PSS10) and anxiety (TAS-20)respectively, which were administered on first-evaluation day, soon after (9.00-9:30am) blood pressure and heart rate measurements (by automatic device) and blood samples withdrawal for PRA, aldosterone and cortisol determinations according to standardized procedures. Results: The scores of the two tests were directly related with each other (p < .0001). For both, a positive association was found with heart rate and a negative one with cortisol levels, more significantly (p < .05 and p < 0.01 respectively) after the exclusion of cases (n = 14) who had positive screening criteria for primary aldosteronism. Anxiety scores were negatively related to cortisol levels particularly in women. No other significant differences or relationships were observed. Conclusions: These preliminary up-to-date results were unable to confirm a significant association between plasma aldosterone and anxiety/stress profiles in hypertensive patients as previously suggested by others. The relationship of anxiety and perceived stress scores with heart rate but not blood pressure levels may be explained by an higher sensitivity of heart rate as an index of sympathetic activation, suggesting it as a sensitive marker of anxiety level in the diagnostic evaluation and follow up of hypertensive patients. Interestingly, in our patients cortisol levels appeared unexpectedly to be negatively related to stress profiles, suggesting a possible primary defect in coping with emotional stress and anxiety in arterial hypertension

Hypotensive Effect Induced by Mandibular Extension in Aged, Hypertensive Humans and Rats

Objectives: Previous research has shown that submaximal mouth opening by mandibular extension (ME) is followed by a prolonged reduction in blood pressure. This effect was observed in young and adult normotensive and hypertensive rats and in young normotensive human subjects. Methods: We assessed the effects of a ME for 10 minutes obtained with a fixed mouth opener in both hypertensive adult humans (aged 55 years or older) and elderly (6-7 months) anaesthetized, hypertensive rats (SHR). Blood pressure and heart rate were measured every 10 minutes by non-invasive automatic recorders for 30 minutes before and 120 minutes after the procedure. Nine human hypertensive subjects (7 experimental and 2 controls) and seven spontaneously hypertensive rats (5 experimental and 2 controls) were tested. Results: A statistically significant reduction in systolic blood pressure (SBP), mean arterial blood pressure (MABP) and heart rate (HR) was observed after ME in the seven hypertensive human subjects, in whom an average decrease of 15 mmHg for SBP, 10 mmHg for MABP and 7 bpm for HR, was observed. A similar hypotensive effect was recorded in spontaneously hypertensive rats that displayed a statistically significant decrease of SBP, DBP and MABP, amounting to about 40-50 mmHg. Conclusion: This study provides the first evidence that ME has an important and prolonged hypotensive effect when applied to subjects with high blood pressure, making their arterial blood pressure decrease toward normal values for at least two hours