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.

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.

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.

Doxycycline ameliorates 2K-1C hypertension-induced vascular dysfunction in rats by attenuating oxidative stress and improving nitric oxide bioavailability

Vascular dysfunction associated with two-kidney, one-clip (2K-1C) hypertension may result from both altered matrix metalloproteinase (MMP) activity and higher concentrations of reactive oxygen species (ROS). Doxycycline is considering the most potent MMP inhibitor of tetracyclines and attenuates 2K-1C hypertension-induced high blood pressure and chronic vascular remodeling. Doxycycline might also act as a ROS scavenger and this may contribute to the amelioration of some cardiovascular diseases associated with increased concentrations of ROS. We hypothesized that in addition to its MMP inhibitory effect, doxycycline attenuates oxidative stress and improves nitric oxide (NO) bioavailability in 2K-1C hypertension, thus improving hypertension-induced arterial endothelial dysfunction. Sham operated or 2K-1C hypertensive rats were treated with doxycycline 30 mg/kg/day (or vehicle). After 8 weeks of treatment, aortic rings were isolated to assess endothelium dependent vasorelaxation to A23187. Arterial and systemic levels of ROS were respectively measured using dihydroethidine (DHE) and thiobarbituric acid reactive substances (TBARS). Neutrophils-derived ROS were tested in vitro using the fluoroprobe Carboxy-H(2)DCFDA and human neutrophils stimulated with phorbol 12-myristate 13-acetate (PMA). NO levels were assessed in rat aortic endothelial cells by confocal microscopy. Aortic MMP activity was determined by in situ zymography. Doxycycline attenuated 2K-1C hypertension (169 +/- 17.3 versus 209 +/- 10.9 mm Hg in hypertensive controls, p < 0.05) and protected against hypertension-induced reduction in endothelium-dependent vasorelaxation to A23187 (p < 0.05). Doxycycline also decreased hypertension-induced oxidative stress (p <= 0.05), higher MMP activity (p < 0.01) and improved NO levels in aortic endothelial cells (p < 0.01). Therefore, doxycycline ameliorates 2K-1C hypertension-induced endothelial dysfunction in aortas by inhibiting oxidative stress generation and improving NO bioavailability, in addition to its inhibitory effects on MMP activity. (C) 2012 Elsevier Inc. All rights reserved.

Amphetamine, cocaine and cannabinoids use among truck drivers on the roads in the State of Sao Paulo, Brazil

Drugs are important risk factors for traffic accidents. In Brazil, truck drivers report using amphetamines to maintain their extensive work schedule and stay awake. These drugs can be obtained without prescription easily on Brazilian roads. The use of these stimulants can result in health problems and can be associated with traffic accidents. There are Brazilian studies that show that drivers use drugs. However, these studies are questionnaire-based and do not always reflect real-life situations. The purpose of this study was to demonstrate the prevalence of drug use by truck drivers on the roads of Sao Paulo State, Brazil, during 2009. Drivers of large trucks were randomly stopped by police officers on the interstate roads during morning hours. After being informed of the goals of the study, the drivers gave written informed consent before providing a urine sample. In addition, a questionnaire concerning sociodemographic characteristics and health information was administered. Urine samples were screened for amphetamines, cocaine, and cannabinoids by immunoassay and the confirmation was performed using gas chromatography-mass spectrometry (GC-MS). Of the 488 drivers stopped, 456 (93.4%) provided urine samples, and 9.3% of them (n = 42) tested positive for drugs. Amphetamines were the most commonly found (n = 26) drug, representing 61.9% of the positive samples. Ten cases tested positive for cocaine (23.8%), and five for cannabinoids (11.9%). All drivers were male with a mean age of 40 +/- 10.8 years, and 29.3% of them reported some health problem (diabetes, high blood pressure and/or stress). A high incidence of truck drivers who tested positive for drug use was found, among other reported health problems. Thus, there is an evident need to promote a healthier lifestyle among professional drivers and a need for preventive measures aimed at controlling the use of drugs by truck drivers in Brazil. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Effect of 12 weeks of resistance exercise on post-exercise hypotension in stage 1 hypertensive individuals

Post-exercise hypotension (PEH), the reduction of blood pressure (BP) after a single bout of exercise, is of great clinical relevance. As the magnitude of this phenomenon seems to be dependent on pre-exercise BP values and chronic exercise training in hypertensive individuals leads to BP reduction; PEH could be attenuated in this context. Therefore, the aim of the present study was to investigate whether PEH remains constant after resistance exercise training. Fifteen hypertensive individuals (46 +/- 8 years; 88 +/- 16 kg; 30 +/- 6% body fat; 150 +/- 13/93 +/- 5mm Hg systolic/diastolic BP, SBP/DBP) were withdrawn from medication and performed 12 weeks of moderate-intensity resistance training. Parameters of cardiovascular function were evaluated before and after the training period. Before the training program, hypertensive volunteers showed significant PEH. After an acute moderate-intensity resistance exercise session with three sets of 12 repetitions (60% of one repetition maximum) and a total of seven exercises, BP was reduced post-exercise (45-60 min) by an average of aproximately -22mm Hg for SBP, -8mm Hg for DBP and -13 mm Hg for mean arterial pressure (P<0.05). However, this acute hypotensive effect did not occur after the 12 weeks of training (P>0.05). In conclusion, our data demonstrate that PEH, following an acute exercise session, can indeed be attenuated after 12 weeks of training in hypertensive stage 1 patients not using antihypertensive medication. Journal of Human Hypertension (2012) 26, 533-539; doi:10.1038/jhh.2011.67; published online 7 July 2011

Sural nerve involvement in experimental hypertension: morphology and morphometry in male and female normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR)

Background: The sural nerve has been widely investigated in experimental models of neuropathies but information about its involvement in hypertension was not yet explored. The aim of the present study was to compare the morphological and morphometric aspects of different segments of the sural nerve in male and female spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Rats aged 20 weeks (N = 6 in each group) were investigated. After arterial pressure and heart rate recordings in anesthetized animals, right and left sural nerves were removed and prepared for epoxy resin embedding and light microscopy. Morphometric analysis was performed with the aid of computer software, and took into consideration the fascicle area and diameter, as well as myelinated fiber number, density, area and diameter. Results: Significant differences were observed for the myelinated fiber number and density, comparing different genders of WKY and SHR. Also, significant differences for the morphological (thickening of the endoneural blood vessel walls and lumen reduction) and morphometric (myelinated fibers diameter and G ratio) parameters of myelinated fibers were identified. Morphological exam of the myelinated fibers suggested the presence of a neuropathy due to hypertension in both SHR genders. Conclusions: These results indicate that hypertension altered important morphometric parameters related to nerve conduction of sural nerve in hypertensive animals. Moreover the comparison between males and females of WKY and SHR allows the conclusion that the morphological and morphometric parameters of sural nerve are not gender related. The morphometric approach confirmed the presence of neuropathy, mainly associated to the small myelinated fibers. In conclusion, the present study collected evidences that the high blood pressure in SHR is affecting the sural nerve myelinated fibers.

Mechanisms of endothelial dysfunction in obesity-associated hypertension

Obesity is strongly associated with high blood pressure, dyslipidemia, and type 2 diabetes. These conditions synergistically increase the risk of cardiovascular events. A number of central and peripheral abnormalities can explain the development or maintenance of high blood pressure in obesity. Of great interest is endothelial dysfunction, considered to be a primary risk factor in the development of hypertension. Additional mechanisms also related to endothelial dysfunction have been proposed to mediate the development of hypertension in obese individuals. These include: increase in both peripheral vasoconstriction and renal tubular sodium reabsorption, increased sympathetic activity and overactivation of both the renin-angiotensin system and the endocannabinoid system and insulin resistance. The discovery of new mechanisms regulating metabolic and vascular function and a better understanding of how vascular function can be influenced by these systems would facilitate the development of new therapies for treatment of obesity-associated hypertension.

GLUT4 content decreases along with insulin resistance and high levels of inflammatory markers in rats with metabolic syndrome

Background: Metabolic syndrome is characterized by insulin resistance, which is closely related to GLUT4 content in insulin-sensitive tissues. Thus, we evaluated the GLUT4 expression, insulin resistance and inflammation, characteristics of the metabolic syndrome, in an experimental model. Methods: Spontaneously hypertensive neonate rats (18/group) were treated with monosodium glutamate (MetS) during 9 days, and compared with Wistar-Kyoto (C) and saline-treated SHR (H). Blood pressure (BP) and lipid levels, C-reactive protein (CRP), interleukin 6 (IL-6), TNF-alpha and adiponectin were evaluated. GLUT4 protein was analysed in the heart, white adipose tissue and gastrocnemius. Studies were performed at 3 (3-mo), 6 (6-mo) and 9 (9-mo) months of age. Results: MetS rats were more insulin resistant (p<0.001, all ages) and had higher BP (3-mo: p<0.001, 6-mo: p = 0.001, 9-mo: p = 0.015) as compared to C. At 6 months, CRP, IL-6 and TNF-alpha were higher (p<0.001, all comparisons) in MetS rats vs H, but adiponectin was lower in MetS at 9 months (MetS: 32 +/- 2, H: 42 +/- 2, C: 45 +/- 2 pg/mL; p<0.001). GLUT4 protein was reduced in MetS as compared to C rats at 3, 6 and 9-mo, respectively (Heart: 54%, 50% and 57%; Gastrocnemius: 37%, 56% and 50%; Adipose tissue: 69%, 61% and 69%). Conclusions: MSG-treated SHR presented all metabolic syndrome characteristics, as well as reduced GLUT4 content, which must play a key role in the impaired glycemic homeostasis of the metabolic syndrome.

Late evaluation of the relationship between morphological and functional renal changes and hypertension after non-operative treatment of high-grade renal injuries

Objective: To evaluate the anatomical and functional renal alterations and the association with post-traumatic arterial hypertension. Methods: The studied population included patients who sustained high grades renal injury (grades III to V) successfully non-operative management after staging by computed tomography over a 16-year period. Beyond the review of medical records, these patients were invited to the following protocol: clinical and laboratory evaluation, abdominal computed tomography, magnetic resonance angiography, DMSA renal scintigraphy, and ambulatory blood pressure monitoring. The hypertensive patients also were submitted to dynamic renal scintigraphy (Tc-99m EC), using captopril stimulation to verify renal vascular etiology. Results: Of the 31 patients, there were thirteen grade III, sixteen grade IV (nine lacerations, and seven vascular lesions), and two grade V injuries. All the patients were asymptomatic and an average follow up post-injury of 6.4 years. None had abnormal BUN or seric creatinine. The percentage of renal volume reduction correlates with the severity as defined by OIS. There was no evidence of renal artery stenosis in Magnetic Resonance angiography (MRA). DMSA scanning demonstrated a decline in percentage of total renal function corresponding to injury severity (42.2 +/- 5.5% for grade III, 35.3 +/- 12.8% for grade IV, 13.5 +/- 19.1 for grade V). Six patients (19.4%) had severe compromised function (< 30%). There was statistically significant difference in the decrease in renal function between parenchymal and vascular causes for grade IV injuries (p < 0.001). The 24-hour ambulatory blood pressure monitoring detected nine patients (29%) with post-traumatic hypertension. All the patients were male, mean 35.6 years, 77.8 % had a familial history of arterial hypertension, 66.7% had grade III renal injury, and average post-injury time was 7.8 years. Seven patients had negative captopril renography. Conclusions: Late results of renal function after conservative treatment of high grades renal injuries are favorable, except for patients with grades IV with vascular injuries and grade V renal injuries. Moreover, arterial hypertension does not correlate with the grade of renal injury or reduction of renal function.

High Cholesterol Feeding May Induce Tubular Dysfunction Resulting in Hypomagnesemia

Background/Aims: Hypomagnesemia may induce hypercholesterolemia, but the contrary has not been described yet. Thus, magnesium homeostasis was evaluated in rats fed a cholesterol-enriched diet for 8 days. This study has a relevant clinical application if hypomagnesemia, due to hypercholesterolemia, is confirmed in patients with long-term hypercholesterolemia. Methods: Both hypercholesterolemic (HC) and normocholesterolemic rats (NC) were divided into sets of experiments to measure hemodynamic parameters, physiological data, maximum capacity to dilute urine (C-H2O), variations (Delta) in [Ca2+](i) and the expression of transporter proteins. Results: HC developed hypomagnesemia and showed high magnesuria in the absence of hemodynamic abnormalities. However, the urinary sodium excretion and C-H2O in HC was similar to NC. On the other hand, the responses to angiotensin II by measuring Delta [Ca2+](i) were higher in the thick ascending limb of Henle's loop (TAL) of HC than NC. Moreover, high expression of the cotransporter NKCC2 was found in renal outer medulla fractions of HC. Taken together, the hypothesis of impairment in TAL was excluded. Actually, the expression of the epithelial Mg2+ channel in renal cortical membrane fractions was reduced in HC. Conclusion: Impairment in distal convoluted tubule induced by hypercholesterolemia explains high magnesuria and hypomagnesemia observed in HC. Copyright (C) 2011 S. Karger AG, Basel

Maternal high-sodium intake alters the responsiveness of the renin-angiotensin system in adult offspring

Aims: The goal of the current study was to evaluate the impact of maternal sodium intake during gestation on the systemic and renal renin-angiotensin-aldosterone-system (RAAS) of the adult offspring. Main methods: Female Wistar rats were fed high- (HSD-8.0% NaCl) or normal-sodium diets (NSD-1.3% NaCl) from 8 weeks of age until the delivery of their first litter. After birth, the offspring received NSD. Tail-cuff blood pressure (TcBP) was measured in the offspring between 6 and 12 weeks of age. At 12 weeks of age, the offspring were subjected to either one week of HSD or low sodium diet (LSD-0.1 6%NaCl) feeding to evaluate RAAS responsiveness or to acute saline overload to examine sodium excretory function. Plasma (PRA) and renal renin content (RRC), serum aldosterone (ALDO) levels, and renal cortical and medullary renin mRNA expression levels were evaluated at the end of the study. Key findings: TcBP was higher among dams fed HSD, but no TcBP differences were observed among the offspring. Male offspring, however, exhibited increased TcBP after one week of HSD feeding, and this effect was independent of maternal diet. Increased RAAS responsiveness to the HSD and LSD was also observed in male offspring. The baseline levels of PRA. ALDO, and cortical and medullary renin gene expression were lower but the RRC levels were higher among HSD-fed male offspring (HSDoff). Conversely, female HSDoff showed reduced sodium excretion 4 h after saline overload compared with female NSDoff. Significance: High maternal sodium intake is associated with gender-specific changes in RAAS responsiveness among adult offspring. (C) 2012 Elsevier Inc. All rights reserved.

A behavioral intervention in a cohort of Japanese-Brazilians at high cardiometabolic risk

OBJECTIVE: To assess the effect of a health promotion program on cardiometabolic risk profile in Japanese-Brazilians. METHODS: A total of 466 subjects from a study on diabetes prevalence conducted in the city of Bauru, southeastern Brazil, in 2000 completed a 1-year intervention program (2005-2006) based on healthy diet counseling and physical activity. Changes in blood pressure and metabolic parameters in the 2005-2006 period were compared with annual changes in these same variables in the 2000-2005 period. RESULTS: During the intervention, there were greater annual reductions in mean (SD) waist circumference [-0.5(3.8) vs. 1.2(1.2) cm per year, p<0.001], systolic blood pressure [-4.6(17.9) vs. 1.8(4.3) mmHg per year, p<0.001], 2-hour plasma glucose [-1.2(2.1) vs. -0.2(0.6) mmol/L per year, p<0.001], LDL-cholesterol [-0.3(0.9) vs. -0.1(0.2) mmol/L per year, p<0.001] and Framingham coronary heart disease risk score [-0.25(3.03) vs. 0.11(0.66) per year, p=0.02] but not in triglycerides [0.2(1.6) vs. 0.1(0.42) mmol/L per year, p<0.001], and fasting insulin level [1.2(5.8) vs. -0.7(2.2) IU/mL per year, p<0.001] compared with the pre-intervention period. Significant reductions in the prevalence of impaired fasting glucose/impaired glucose tolerance and diabetes were seen during the intervention (from 58.4% to 35.4%, p<0.001; and from 30.1% to 21.7%, p= 0.004, respectively). CONCLUSIONS: A one-year community-based health promotion program brings cardiometabolic benefits in a high-risk population of Japanese-Brazilians.