Felypressin Increases Blood Pressure During Dental Procedures in Hypertensive Patients

Background: Felypressin has been added to local anesthetic to increase the length of the anesthetic effect and reduce toxicity during dental procedures. However, the effect on blood pressure remains uncertain, and this may be highly relevant in the dental treatment of hypertensive patients. Objective: To investigate the effect of felypressin on blood pressure in hypertensive patients with controlled BP. Methods: 71 subjects with these characteristics and in need of periodontal treatment were studied. After 10 minutes of rest, local anesthesia (prilocaine) was infiltrated with and without addition of felypressin. Then, a deep subgingival scaling was performed. Blood pressure was measured by an automated oscillometric device (DIXTAL DX2010). Ten minutes after the administration of the anesthetic, peak anesthetic action was recorded. The State-Trait Anxiety Inventory (STAI) was used to assess the patients' trait anxiety. Results: Systolic blood pressure increased after anesthesia, regardless of association with felypressin, throughout the dental procedure (p<0.05) and this response can be explained, at least in part, by the trait anxiety levels of the subjects. However, a further increase in diastolic blood pressure was observed when prilocaine was associated with felypressin (p<0.05), but this response did not change with trait anxiety levels. Conclusion: Felypressin increased the diastolic blood pressure of hypertensive patients with controlled blood pressure. Patients with high trait anxiety presented increases in systolic blood pressure upon some procedures, suggesting that an increase in blood pressure might also be related to fear or anxiety. (Arq Bras Cardiol 2012;99(2):724-731)

Exercise training program based on minimum weekly frequencies: effects on blood pressure and physical fitness in elderly hypertensive patients

Background: Exercise training (ET) can reduce blood pressure (BP) and prevent functional disability. However, the effects of low volumes of training have been poorly studied, especially in elderly hypertensive patients. Objectives: To investigate the effects of a multi-component ET program (aerobic training, strength, flexibility, and balance) on BP, physical fitness, and functional ability of elderly hypertensive patients. Methods: Thirty-six elderly hypertensive patients with optimal clinical treatment underwent a multi-component ET program: two 60-minute sessions a week for 12 weeks at a Basic Health Unit. Results: Compared to pre-training values, systolic and diastolic BP were reduced by 3.6% and 1.2%, respectively (p < 0.001), body mass index was reduced by 1.1% (p < 0.001), and peripheral blood glucose was reduced by 2.5% (p= 0.002). There were improvements in all physical fitness domains: muscle strength (chair-stand test and elbow flexor test; p < 0.001), static balance test (unipedal stance test; p < 0.029), aerobic capacity (stationary gait test; p < 0.001), except for flexibility (sit and reach test). Moreover, there was a reduction in the time required to perform two functional ability tests: "put on sock" and "sit down, stand up, and move around the house" (p < 0.001). Conclusions: Lower volumes of ET improved BP, metabolic parameters, and physical fitness and reflected in the functional ability of elderly hypertensive patients. Trial Registration RBR-2xgjh3.

Is income area level associated with blood pressure in adults regardless of individual-level characteristics? A multilevel approach

This population-based health survey was carried out in Florianopolis, Brazil, to assess the association between adult systolic blood pressure (SBP) and contextual income level, after controlling for potential individual-level confounders. A statistically significant negative association between SBP levels and contextual income was identified after adjusting for individual-level characteristics. SBP levels in the highest and in the intermediate tertiles of contextual income were 5.78 and 2.82 mmHg lower, respectively, than that observed in the bottom tertile. The findings suggest an association between income area level and blood pressure, regardless of well-known individual-level hypertension risk factors. (C) 2012 Elsevier Ltd. All rights reserved.

Blood Pressure, Metabolic and Autonomic Responses to Insulin and Intralipid (R) Infusion in Chagasic Patients

Background: Intralipid (R) and heparin infusion results in increased blood pressure and autonomic abnormalities in normal and hypertensive individuals. Objective: To evaluate insulin sensitivity and the impact of Intralipid (R) and heparin (ILH) infusion on hemodynamic, metabolic, and autonomic response in patients with the indeterminate form of Chagas' disease. Methods: Twelve patients with the indeterminate form of Chagas' disease and 12 healthy volunteers were evaluated. Results: Baseline blood pressure and heart rate were similar in both groups. Plasma noradrenaline levels were slightly increased in the Chagas' group. After insulin tolerance testing (ITT), a significant decline was noted in glucose in both groups. ILH infusion resulted in increased blood pressure in both groups, but there was no significant change in plasma noradrenaline. The low-frequency component (LF) was similar and similarly increased in both groups. The high-frequency component (HF) was lower in the Chagas' group. Conclusion: Patients with the indeterminate form of Chagas' disease had increased sympathetic activity at baseline and impaired response to insulin. They also had a lower high-frequency component and impaired baroreflex sensitivity at baseline and during Intralipid (R) and heparin infusion. (Arq Bras Cardiol 2012;98(3):225-233)

Ambulatory blood pressure monitoring in children with obstructive sleep apnea and primary snoring

Objective: To evaluate the systemic blood pressure (BP) during daytime and nighttime in children with sleep breathing disorders (SBD) and compare parameters of BP in children with diagnosis of obstructive sleep apnea syndrome (OSA) to those one with primary snoring (PS). Methods: Children, both genders, aged from 8 to 12 years, with symptoms of SBD realized an overnight polysomnography followed by a 24 h recording of ambulatory BP. Results: All subjects presented with a history of snoring 7 nights per week. Children who have apnea/hipoapnea index >= four or a apnea index >= one presented a mean BP of 93 +/- 7 mmHg and 85 +/- 9 mmHg diurnal and nocturnal respectively whereas children who have a apnea/hipoapnea < four or a apnea index < one presented 90 +/- 7 mmHg and 77 +/- 2 mmHg. Eight children out of fourteen, from OSA group, lost the physiologic nocturnal dipping of the blood pressure. Among OSA children 57% were considered non-dippers. Two (16%) have presented absence of nocturnal dipping among children with primary snoring. The possibility of OSA children loosing physiologic blood pressure dipping was 6.66 higher than the possibilities of patients from PS group. Discussion: Our results indicate that children with sleep apnea syndrome exhibit a higher 24 h blood pressure when compared with those of primary snoring in form of decreased degree of nocturnal dipping and increased levels of diastolic and mean blood pressure, according to previous studies in literature. OSA in children seems to be associated to the development of hypertension or other cardiovascular disease. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Longitudinal familial analysis of blood pressure involving parametric (co)variance functions

Abstract Background For analyzing longitudinal familial data we adopted a log-linear form to incorporate heterogeneity in genetic variance components over the time, and additionally a serial correlation term in the genetic effects at different levels of ages. Due to the availability of multiple measures on the same individual, we permitted environmental correlations that may change across time. Results Systolic blood pressure from family members from the first and second cohort was used in the current analysis. Measures of subjects receiving hypertension treatment were set as censored values and they were corrected. An initial check of the variance and covariance functions proposed for analyzing longitudinal familial data, using empirical semi-variogram plots, indicated that the observed trait dispersion pattern follows the assumptions adopted. Conclusion The corrections for censored phenotypes based on ordinary linear models may be an appropriate simple model to correct the data, ensuring that the original variability in the data was retained. In addition, empirical semi-variogram plots are useful for diagnosis of the (co)variance model adopted.

Gene by environment QTL mapping through multiple trait analyses in blood pressure salt-sensitivity: identification of a novel QTL in rat chromosome 5

Background The genetic mechanisms underlying interindividual blood pressure variation reflect the complex interplay of both genetic and environmental variables. The current standard statistical methods for detecting genes involved in the regulation mechanisms of complex traits are based on univariate analysis. Few studies have focused on the search for and understanding of quantitative trait loci responsible for gene × environmental interactions or multiple trait analysis. Composite interval mapping has been extended to multiple traits and may be an interesting approach to such a problem. Methods We used multiple-trait analysis for quantitative trait locus mapping of loci having different effects on systolic blood pressure with NaCl exposure. Animals studied were 188 rats, the progenies of an F2 rat intercross between the hypertensive and normotensive strain, genotyped in 179 polymorphic markers across the rat genome. To accommodate the correlational structure from measurements taken in the same animals, we applied univariate and multivariate strategies for analyzing the data. Results We detected a new quantitative train locus on a region close to marker R589 in chromosome 5 of the rat genome, not previously identified through serial analysis of individual traits. In addition, we were able to justify analytically the parametric restrictions in terms of regression coefficients responsible for the gain in precision with the adopted analytical approach. Conclusion Future work should focus on fine mapping and the identification of the causative variant responsible for this quantitative trait locus signal. The multivariable strategy might be valuable in the study of genetic determinants of interindividual variation of antihypertensive drug effectiveness.

The relationship between training status, blood pressure and uric acid in adults and elderly

Abstract Background Hypertension can be generated by a great number of mechanisms including elevated uric acid (UA) that contribute to the anion superoxide production. However, physical exercise is recommended to prevent and/or control high blood pressure (BP). The purpose of this study was to investigate the relationship between BP and UA and whether this relationship may be mediated by the functional fitness index. Methods All participants (n = 123) performed the following tests: indirect maximal oxygen uptake (VO2max), AAHPERD Functional Fitness Battery Test to determine the general fitness functional index (GFFI), systolic and diastolic blood pressure (SBP and DBP), body mass index (BMI) and blood sample collection to evaluate the total-cholesterol (CHOL), LDL-cholesterol (LDL-c), HDL-cholesterol (HDL-c), triglycerides (TG), uric acid (UA), nitrite (NO2) and thiobarbituric acid reactive substances (T-BARS). After the physical, hemodynamic and metabolic evaluations, all participants were allocated into three groups according to their GFFI: G1 (regular), G2 (good) and G3 (very good). Results Baseline blood pressure was higher in G1 when compared to G3 (+12% and +11%, for SBP and DBP, respectively, p<0.05) and the subjects who had higher values of BP also presented higher values of UA. Although UA was not different among GFFI groups, it presented a significant correlation with GFFI and VO2max. Also, nitrite concentration was elevated in G3 compared to G1 (140±29 μM vs 111± 29 μM, for G3 and G1, respectively, p<0.0001). As far as the lipid profile, participants in G3 presented better values of CHOL and TG when compared to those in G1. Conclusions Taking together the findings that subjects with higher BP had elevated values of UA and lower values of nitrite, it can be suggested that the relationship between blood pressure and the oxidative stress produced by acid uric may be mediated by training status.

Genetic and environmental influences on blood pressure and physical activity: a study of nuclear families from Muzambinho, Brazil

Blood pressure (BP) and physical activity (PA) levels are inversely associated. Since genetic factors account for the observed variation in each of these traits, it is possible that part of their association may be related to common genetic and/or environmental influences. Thus, this study was designed to estimate the genetic and environmental correlations of BP and PA phenotypes in nuclear families from Muzambinho, Brazil. Families including 236 offspring (6 to 24 years) and their 82 fathers and 122 mothers (24 to 65 years) were evaluated. BP was measured, and total PA (TPA) was assessed by an interview (commuting, occupational, leisure time, and school time PA). Quantitative genetic modeling was used to estimate maximal heritability (h²), and genetic and environmental correlations. Heritability was significant for all phenotypes (systolic BP: h² = 0.37 ± 0.10, P < 0.05; diastolic BP: h² = 0.39 ± 0.09, P < 0.05; TPA: h² = 0.24 ± 0.09, P < 0.05). Significant genetic (r g) and environmental (r e) correlations were detected between systolic and diastolic BP (r g = 0.67 ± 0.12 and r e = 0.48 ± 0.08, P < 0.05). Genetic correlations between BP and TPA were not significant, while a tendency to an environmental cross-trait correlation was found between diastolic BP and TPA (r e = -0.18 ± 0.09, P = 0.057). In conclusion, BP and PA are under genetic influences. Systolic and diastolic BP share common genes and environmental influences. Diastolic BP and TPA are probably under similar environmental influences.

Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats

High systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threonine kinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-α (TNFα) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNFα-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-κB (Iκβ) and c-Jun N-terminal kinase (JNK) in the aorta. Overall, our study revealed the cardiovascular benefits of infliximab in SHR. In addition, the present findings further suggested that the reduction of systolic pressure and left ventricle hypertrophy by infliximab are secondary effects to the reduction of endothelial inflammation and the recovery of AKT/eNOS pathway activation.

P2Y1 receptors expressed by C1 neurons determine peripheral chemoreceptor modulation of breathing, sympathetic activity, and blood pressure

Catecholaminergic C1 cells of the rostral ventrolateral medulla (RVLM) are key determinants of the sympathoexcitatory response to peripheral chemoreceptor activation. Overactivation of this reflex is thought to contribute to increased sympathetic activity and hypertension; however, molecular mechanisms linking peripheral chemoreceptor drive to hypertension remain poorly understood. We have recently determined that activation of P2Y1 receptors in the RVLM mimicked effects of peripheral chemoreceptor activation. Therefore, we hypothesize that P2Y1 receptors regulate peripheral chemoreceptor drive in this region. Here, we determine whether P2Y1 receptors are expressed by C1 neurons in the RVLM and contribute to peripheral chemoreceptor control of breathing, sympathetic activity, and blood pressure. We found that injection of a specific P2Y1 receptor agonist (MRS2365) into the RVLM of anesthetized adult rats increased phrenic nerve activity (≈55%), sympathetic nerve activity (38±6%), and blood pressure (23±1 mm Hg), whereas application of a specific P2Y1 receptor antagonist (MRS2179) decreased peripheral chemoreceptor–mediated activation of phrenic nerve activity, sympathetic nerve activity, and blood pressure. To establish that P2Y1 receptors are expressed by C1 cells, we determine in the brain slice preparation using cell-attached recording techniques that cells responsive to MRS2365 are immunoreactive for tyrosine hydroxylase (a marker of C1 cells), and we determine in vivo that C1-lesioned animals do not respond to RVLM injection of MRS2365. These data identify P2Y1 receptors as key determinants of peripheral chemoreceptor regulation of breathing, sympathetic nerve activity, and blood pressure.

Chronic hypoxia increases blood pressure and noradrenaline spillover in healthy humans

[EN] Chronic hypoxia is associated with elevated sympathetic activity and hypertension in patients with chronic pulmonary obstructive disease. However, the effect of chronic hypoxia on systemic and regional sympathetic activity in healthy humans remains unknown. To determine if chronic hypoxia in healthy humans is associated with hyperactivity of the sympathetic system, we measured intra-arterial blood pressure, arterial blood gases, systemic and skeletal muscle noradrenaline (norepinephrine) spillover and vascular conductances in nine Danish lowlanders at sea level and after 9 weeks of exposure at 5260 m. Mean blood pressure was 28 % higher at altitude (P < 0.01) due to increases in both systolic (18 % higher, P < 0.05) and diastolic (41 % higher, P < 0.001) blood pressures. Cardiac output and leg blood flow were not altered by chronic hypoxia, but systemic vascular conductance was reduced by 30 % (P < 0.05). Plasma arterial noradrenaline (NA) and adrenaline concentrations were 3.7- and 2.4-fold higher at altitude, respectively (P < 0.05). The elevation of plasma arterial NA concentration was caused by a 3.8-fold higher whole-body NA release (P < 0.001) since whole-body noradrenaline clearance was similar in both conditions. Leg NA spillover was increased similarly (x 3.2, P < 0.05). These changes occurred despite the fact that systemic O2 delivery was greater after altitude acclimatisation than at sea level, due to 37 % higher blood haemoglobin concentration. In summary, this study shows that chronic hypoxia causes marked activation of the sympathetic nervous system in healthy humans and increased systemic arterial pressure, despite normalisation of the arterial O2 content with acclimatisation.

Sleep-related changes in blood pressure in hypocretin-deficient narcoleptic mice

Objectives. Blood pressure (BP) physiologically has higher and lower values during the active and rest period, respectively. Subjects failing to show the appropriate BP decrease (10-20%) on passing form diurnal activity to nocturnal rest and sleep have increased risk of target organ damage at the cardiac, vascular and cerebrovascular levels. Hypocretin (HCRT) releasing neurons, mainly located in the lateral hypothalamus, project widely to the central nervous system. Thus HCRT neurons are involved in several autonomic functions, including BP regulation. HCRT neurons also play a key role in wake-sleep cycle regulation, the lack of which becomes evident in HCRT-deficient narcoleptic patients. I investigated whether chronic lack of HCRT signaling alters BP during sleep in mouse models of narcolepsy. Methods. The main study was performed on HCRT-ataxin3 transgenic mice (TG) with selective post-natal ablation of HCRT neurons, HCRT gene knockout mice (KO) with preserved HCRT neurons, and Wild-Type control mice (WT) with identical genetic background. Experiments where replicated on TG and WT mice with hybrid genetic background (hTG and hWT, respectively). Mice were implanted with a telemetric pressure transducer (TA11PA-C10, DSI) and electrodes for discriminating wakefulness (W), rapid-eye-movement sleep (REMS) and non-REMS (NREMS). Signals were recorded for 3 days. Mean BP values were computed in each wake-sleep state and analyzed by ANOVA and t-test with significance at p<0.05. Results. The decrease in BP between either NREMS or REMS and W was significantly blunted in TG and KO with respect to WT as well as in hTG with respect to hWT. Conclusions. Independently from the genetic background, chronic HCRT deficiency leads to a decreased BP difference between W and sleep potentially adverse in narcoleptic subjects. These data suggest that HCRT play an important role in the sleep-dependent cardiovascular control.