Control Of Arterial Blood Pressure Research Articles

Systemic and renal oxidative stress in the pathogenesis of hypertension: modulation of long-term control of arterial blood pressure by resveratrol.

Hypertension affects over 25% of the global population and is associated with grave and often fatal complications that affect many organ systems. Although great advancements have been made in the clinical assessment and treatment of hypertension, the cause of hypertension in over 90% of these patients is unknown, which hampers the development of targeted and more effective treatment. The etiology of hypertension involves multiple pathological processes and organ systems, however one unifying feature of all of these contributing factors is oxidative stress. Once the body's natural anti-oxidant defense mechanisms are overwhelmed, reactive oxygen species (ROS) begin to accumulate in the tissues. ROS play important roles in normal regulation of many physiological processes, however in excess they are detrimental and cause widespread cell and tissue damage as well as derangements in many physiological processes. Thus, control of oxidative stress has become an attractive target for pharmacotherapy to prevent and manage hypertension. Resveratrol (trans-3,5,4′-Trihydroxystilbene) is a naturally occurring polyphenol which has anti-oxidant effects in vivo. Many studies have shown anti-hypertensive effects of resveratrol in different pre-clinical models of hypertension, via a multitude of mechanisms that include its function as an anti-oxidant. However, results have been mixed and in some cases resveratrol has no effect on blood pressure. This may be due to the heavy emphasis on peripheral vasodilator effects of resveratrol and virtually no investigation of its potential renal effects. This is particularly troubling in the arena of hypertension, where it is well known and accepted that the kidney plays an essential role in the long term regulation of arterial pressure and a vital role in the initiation, development and maintenance of chronic hypertension. It is thus the focus of this review to discuss the potential of resveratrol as an anti-hypertensive treatment via amelioration of oxidative stress within the framework of the fundamental physiological principles of long term regulation of arterial blood pressure.

Epithelial sodium channel modulates platelet collagen activation

Activated platelets adhere to the exposed subendothelial extracellular matrix and undergo a rapid cytoskeletal rearrangement resulting in shape change and release of their intracellular dense and alpha granule contents to avoid hemorrhage. A central step in this process is the elevation of the intracellular Ca2+ concentration through its release from intracellular stores and on throughout its influx from the extracellular space. The Epithelial sodium channel (ENaC) is a highly selective Na+ channel involved in mechanosensation, nociception, fluid volume homeostasis, and control of arterial blood pressure. The present study describes the expression, distribution, and participation of ENaC in platelet migration and granule secretion using pharmacological inhibition with amiloride. Our biochemical and confocal analysis in suspended and adhered platelets suggests that ENaC is associated with Intermediate filaments (IF) and with Dystrophin-associated proteins (DAP) via α-syntrophin and β-dystroglycan. Migration assays, quantification of soluble P-selectin, and serotonin release suggest that ENaC is dispensable for migration and alpha and dense granule secretion, whereas Na+ influx through this channel is fundamental for platelet collagen activation.

Gap junction regulation of vascular tone: implications of modulatory intercellular communication during gestation.

In the vasculature, gap junctions (GJ) play a multifaceted role by serving as direct conduits for cell-cell intercellular communication via the facilitated diffusion of signaling molecules. GJs are essential for the control of gene expression and coordinated vascular development in addition to vascular function. The coupling of endothelial cells to each other, as well as with vascular smooth muscle cells via GJs, plays a relevant role in the control of vasomotor tone, tissue perfusion and arterial blood pressure. The regulation of cell-signaling is paramount to cardiovascular adaptations of pregnancy. Pregnancy requires highly developed cell-to-cell coupling, which is affected partly through the formation of intercellular GJs by Cx43, a gap junction protein, within adjacent cell membranes to help facilitate the increase of uterine blood flow (UBF) in order to ensure adequate perfusion for nutrient and oxygen delivery to the placenta and thus the fetus. One mode of communication that plays a critical role in regulating Cx43 is the release of endothelial-derived vasodilators such as prostacyclin (PGI2) and nitric oxide (NO) and their respective signaling mechanisms involving second messengers (cAMP and cGMP, respectively) that are likely to be important in maintaining UBF. Therefore, the assertion we present in this review is that GJs play an integral if not a central role in maintaining UBF by controlling rises in vasodilators (PGI2 and NO) via cyclic nucleotides. In this review, we discuss: (1) GJ structure and regulation; (2) second messenger regulation of GJ phosphorylation and formation; (3) pregnancy-induced changes in cell-signaling; and (4) the role of uterine arterial endothelial GJs during gestation. These topics integrate the current knowledge of this scientific field with interpretations and hypotheses regarding the vascular effects that are mediated by GJs and their relationship with vasodilatory vascular adaptations required for modulating the dramatic physiological rises in uteroplacental perfusion and blood flow observed during normal pregnancy.

Closed and open loop mechanisms controlling arterial blood pressure in waking state in human and experimental animal

Time-honored indices of classical, closed loop arterial blood pressure (BPa) control have recently been supplemented by analyses thought to be sensitive to both closed and open loop mechanisms. These newer tools include, among others, power spectral analyses of heart rate (HR) and BPa, and the cross-correlation between changes in BPa and changes in HR or R-R interval. The „baroreceptor effectiveness index‟ (BEI) is significantly larger in supine, healthy individuals as compared to diabetic patients with peripheral neuropathy. Such findings give promise that BEI may provide a means to assess the development of autonomic neuropathy in diabetic or in other at-risk patients. The cross-correlation between BPa and heart rate in man includes a peak where the two are positively correlated with HR changes leading pressure changes, suggestive of open loop control, and a sharp nadir where the two are negatively correlated and BPa changes precede HR changes, suggestive of closed loop control. In rat the positive cross-correlation depends upon intact spinal sympathetic pathways. The magnitudes of both the positive and negative cross correlations are weaker in tetraplegic patients as compared to neutrally intact subjects. Both peaks remain relatively strong in healthy subjects during the challenge of head up tilt, but decline precipitously in tetraplegic patients. The recognition that both closed and open loop mechanisms are operative and functionally important suggests multiple additional possible etiologies for cardiovascular dysfunctions, including hypertension. The advent of non-invasive means to quantify autonomic function promises new insights into control of the cardiovascular system in health and disease

A computational analysis of the long-term regulation of arterial pressure

The asserted dominant role of the kidneys in the chronic regulation of blood pressure and in the etiology of hypertension has been debated since the 1970s. At the center of the theory is the observation that the acute relationships between arterial pressure and urine production—the acute pressure-diuresis and pressure-natriuresis curves—physiologically adapt to perturbations in pressure and/or changes in the rate of salt and volume intake. These adaptations, modulated by various interacting neurohumoral mechanisms, result in chronic relationships between water and salt excretion and pressure that are much steeper than the acute relationships. While the view that renal function is the dominant controller of arterial pressure has been supported by computer models of the cardiovascular system known as the “Guyton-Coleman model”, no unambiguous description of a computer model capturing chronic adaptation of acute renal function in blood pressure control has been presented. Here, such a model is developed with the goals of: 1. representing the relevant mechanisms in an identifiable mathematical model; 2. identifying model parameters using appropriate data; 3. validating model predictions in comparison to data; and 4. probing hypotheses regarding the long-term control of arterial pressure and the etiology of primary hypertension. The developed model reveals: long-term control of arterial blood pressure is primarily through the baroreflex arc and the renin-angiotensin system; and arterial stiffening provides a sufficient explanation for the etiology of primary hypertension associated with ageing. Furthermore, the model provides the first consistent explanation of the physiological response to chronic stimulation of the baroreflex.

A computational analysis of the long-term regulation of arterial pressure

The asserted dominant role of the kidneys in the chronic regulation of blood pressure and in the etiology of hypertension has been debated since the 1970s. At the center of the theory is the observation that the acute relationships between arterial pressure and urine production—the acute pressure-diuresis and pressure-natriuresis curves—physiologically adapt to perturbations in pressure and/or changes in the rate of salt and volume intake. These adaptations, modulated by various interacting neurohumoral mechanisms, result in chronic relationships between water and salt excretion and pressure that are much steeper than the acute relationships. While the view that renal function is the dominant controller of arterial pressure has been supported by computer models of the cardiovascular system known as the “Guyton-Coleman model”, no unambiguous description of a computer model capturing chronic adaptation of acute renal function in blood pressure control has been presented. Here, such a model is developed with the goals of: 1. capturing the relevant mechanisms in an identifiable mathematical model; 2. identifying model parameters using appropriate data; 3. validating model predictions in comparison to data; and 4. probing hypotheses regarding the long-term control of arterial pressure and the etiology of primary hypertension. The developed model reveals: long-term control of arterial blood pressure is primarily through the baroreflex arc and the renin-angiotensin system; and arterial stiffening provides a sufficient explanation for the etiology of primary hypertension associated with ageing. Furthermore, the model provides the first consistent explanation of the physiological response to chronic stimulation of the baroreflex.

Baroreceptor sensitivity and diabetes mellitus

Diabetes mellitus (DM) is a disease of increasing incidence and prevalence. Arterial baroreceptors are stretch-sensitive receptors, which in a reflex manner are involved in the homeostatic control of arterial blood pressure. Diabetic subjects have depressed baroreflex sensitivity (BRS), although the exact pathomechanisms are unclear. In this review, we discuss the features, clinicaland prognostic implications of reduced BRS for diabetic patients and the potential involvement of cardiovascular autonomic neuropathy and atherosclerosis. Finally, we demonstrate evidence on interventions (e.g. pioglitazone, alpha-lipoic acid, leptin, fluvastatin, physicaltraining etc.) which could improve BRS and ameliorate cardiovascular autonomic dysfunction in diabetic patients.

Nephroprotective action of sirtuin 1 (SIRT1)

Sirtuins, silent information regulator 2 (Sir 2) proteins, belong to the family of NAD(+)-dependent enzymes with deacetylase or mono-ADP-ribosyltransferase activity. These enzymes are responsible for processes of DNA repair or recombination, chromosomal stability and gene transcription. In mammals, sirtuins occur in seven varieties, from 1 to 7 (SIRT1-SIRT7), differing among themselves with location. SIRT1, the best known variety, exerts its effects on proteins via NAD(+) coenzymes, being thus associated with cellular energetic metabolism and the 'red-ox' state. Its deficits are, among others, concomitant with stressful situations and associated with pathophysiologies of many medical conditions, including diabetes mellitus, cardiovascular diseases, neurodegenerative syndromes and kidney diseases. In kidney disorders, it promotes (stimulates) the survival of cells in an affected kidney by modulating their responses to various stress stimuli, takes part in arterial blood pressure control, protects against cellular apoptosis in renal tubules by catalase induction and triggers autophagy. More and more available in vitro and in vivo data indicate SIRT1 activity to be oriented, among others, towards nephroprotection. Thus, SIRT1 may become a novel element in the therapy of age-related renal diseases, including diabetic nephropathy.

Endothelin-1 inhibits sodium reabsorption by ETAand ETBreceptors in the mouse cortical collecting duct

The collecting duct (CD) is a major renal site for the hormonal regulation of Na homeostasis and is critical for systemic arterial blood pressure control. Our previous studies demonstrated that the endothelin-1 gene (edn1) is an early response gene to the action of aldosterone. Because aldosterone and endothelin-1 (ET-1) have opposing actions on Na reabsorption (JNa) in the kidney, we postulated that stimulation of ET-1 by aldosterone acts as a negative feedback mechanism, acting locally within the CD. Aldosterone is known to increase JNa in the CD, in part, by stimulating the epithelial Na channel (ENaC). In contrast, ET-1 increases Na and water excretion through its binding to receptors in the CD. To date, direct measurement of the quantitative effect of ET-1 on transepithelial JNa in the isolated in vitro microperfused mouse CD has not been determined. We observed that the CD exhibits substantial JNa in male and female mice that is regulated, in part, by a benzamil-sensitive pathway, presumably ENaC. ENaC-mediated JNa is greater in the cortical CD (CCD) than in the outer medullary CD (OMCD); however, benzamil-insensitive JNa is present in the CCD and not in the OMCD. In the presence of ET-1, ENaC-mediated JNa is significantly inhibited. Blockade of either ETA or ETB receptor restored JNa to control rates; however, only ETA receptor blockade restored a benzamil-sensitive component of JNa. We conclude 1) Na reabsorption is mediated by ENaC in the CCD and OMCD and also by an ENaC-independent mechanism in the CCD; and 2) ET-1 inhibits JNa in the CCD through both ETA and ETB receptor-mediated pathways.

Role of adrenergic neurotransmission in the Median Preoptic Nucleus in experimental hypertension

The present study sought to determine the involvement of the adrenergic neurotransmission in the Median Preoptic Nucleus (MnPO) in arterial blood pressure (MAP) control in normotensive and spontaneously hypertensive rats (SH). Male Wistar normotensive (NT) and SH rats (250–320g) were anesthetized with urethane (1.2 g/kg, i.v.) and instrumented for recordings of MAP, aortic blood flow (ABF) and renal (RBF). The rats were fixed in a stereotaxic apparatus and made nanoinjections (100 nl) of saline (0. 15 M) and Fentolamina (6.3 mM; α‐adrenergic antagonist). Aortic vascular conductance (AVC) and renal (RVC) was calculated as the ratio ABF or RBF/MAP and expressed as percentage of baseline. The results demonstrated that adrenergic neurotransmission blocking in MnPO resulted in a decrease in MAP (−7.7 ± 1.1 mmHg, n=7), ABF (−7.3 ± 2.0% above baseline, n=5) and RBF (−7.2 ± 2.1% above baseline, n = 7) of NT rats. In SH also observed decrease in MAP (−14.3 ± 6 mmHg, n = 6) and increase in AVC (8.3 ± 3.0% above baseline, n=5) and RVC (9.6 ± 1.9% above baseline, n=6), indicating vasodilation. These results suggest the participation of MnPO in tonic regulation of blood pressure in NT and SH rats.

The Effect of Blood Pressure Regulation During Aortic Coarctation Repair on Brain, Kidney, and Muscle Oxygen Saturation Measured by Near-Infrared Spectroscopy

In this study, we compared the effects of 3 frequently used arterial blood pressure-regulating agents on brain (rScO2), renal (SrO2), and muscle (SmO2) oxygen saturation, during aortic coarctation repair in children. Based on the reported adverse effect of sodium nitroprusside (SNP) on left-sided rScO2 during aortic coarctation repair, we tested the hypothesis that the alterations in left rScO2 occurring with SNP would not be present with sevoflurane and nitroglycerin (NTG). Additionally, we explored the effects of blood pressure regulation with SNP, NTG, or sevoflurane on right-sided rScO2, SrO2, and SmO2. Children with isolated aortic coarctation undergoing surgical repair through a left thoracotomy without the use of cardiopulmonary bypass were considered eligible for the study. During aortic cross-clamping, control of mean arterial blood pressure (MAP) was conducted according to randomization by the use of SNP, NTG, or sevoflurane to obtain a mean target right brachial blood pressure of 120% to 150% of the MAP value before cross-clamping. Bilateral rScO2, SrO2, and SmO2 were recorded continuously with near-infrared spectroscopy. As a primary end point, the maximal relative change in left-sided rScO2 in response to aortic cross-clamping was compared among treatment groups. Ten patients per group were included. No significant difference among treatment groups was observed in maximal relative change in left-sided rScO2 (SNP versus sevoflurane: mean difference -0.7%, 99% confidence interval [CI] -31% to 29%, P = 1.0; SNP versus NTG: mean difference -1.8%, 99% CI -32% to 28%, P = 1.0; sevoflurane versus NTG: mean difference -1.1%, 99% CI -31% to 29%, P = 1.0). Additional analyses also detected no difference between groups in right rScO2 (P = 0.4). Compared with NTG, treatment with SNP resulted in a significantly larger (-64% ± 17% vs -34% ± 25%, P = 0.01) and faster (-9 ± 4 %·min(-1) vs -4 ± 3 %·min(-1), P = 0.004) decrease in SmO2. Right-sided rScO2 and MAP showed a poor correlation for NTG (r = -0.2, P = 0.93), whereas borderline for sevoflurane (r = 0.44, P = 0.09) and SNP (r = 0.56, P = 0.04). The mean differences in left-sided rScO2 among the patients treated with SNP, NTG, or sevoflurane for proximal hypertension during aortic cross-clamping were no more than 32%. Additional analysis demonstrated a low MAP-rScO2 dependence with the use of NTG. Because NTG also resulted in a smaller and slower decrease of oxygen saturation in peripheral tissues, our data suggest that its use might be preferable for proximal blood pressure control during surgical procedures involving aortic cross-clamping.

Cardiovascular Rehabilitation, Ballroom Dancing and Sexual Dysfunction

Sexual dysfunction is an important public health concern, highly prevalent among men and women1,2. It is related to the major cardiovascular and metabolic diseases eligible for cardiopulmonary and metabolic rehabilitation (CPMR), such as systemic arterial hypertension, coronary arterial disease, heart failure, and diabetes mellitus3,4. Of the vascular, structural and functional abnormalities related to sexual dysfunction, the following stand out: endothelial changes; systolic pressure elevation; and atherosclerosis5. Sexual function is a good parameter to assess the treatment of cardiovascular diseases, known to improve the quality of life of patients6, most of whom show interest in maintaining an active sexual life. Nevertheless, the manifestations of sexuality are usually underestimated by physicians and other health care professionals, in part due to cultural aspects, taboos and prejudice7. That should change, because, after a cardiovascular event or intervention, the instructions about sexual activity are as relevant as those concerning return to work and engagement into exercise programs8. The complexity of that relationship and the need for instructions have become evident in studies, such as the COPE-ICD, which reported, contrary to the expected, expressive sexual function worsening in patients of both sexes who underwent defibrillator implantation8. Historically, the medicamentous treatment of cardiovascular diseases has been associated with worse sexual performance5,9,10. However, the new generation medications, such as modern beta-blockers (nebivolol and bisoprolol), diuretics (indapamide) and angiotensin-receptor blockers, seem to contribute to improve erectile dysfunction, especially by improving endothelial function and increasing cardiac fitness10,11, enabling the simultaneous treatment of sexual dysfunction. Sexual function is mediated by a complex interaction of psychological and physiological factors (hormonal, vascular, muscular and neurological), which might all be influenced by exercise3, emphasis given to the greater production and lower degradation of nitric oxide, considered the major mediator of male and female sexual function12. It is worth noting that research related to exercise and sexual function has shown that high doses of physical activity reduce the risk of acute myocardial infarction and sudden death during sexual intercourse13. In addition, among young men, those with better cardiorespiratory fitness are less susceptible to erectile dysfunction14. Thus, it is evident that physical exercise should be included among the interventions that benefit cardiovascular and sexual health11. The effects of exercise on physical fitness, endothelial function, autonomic modulation and emotional aspects (anxiety, depression, self-esteem) evidence the broad spectrum of action of exercise, resulting beneficial for the treatment of cardiovascular and metabolic diseases, as well as for the management of sexual dysfunction. However, the conventional forms of physical exercise offered in CPMR programs seem little attractive to provide the necessary adherence to treatment, justifying the search for new strategies3,15-19. In that context, ballroom dancing, a popular, ludic, pleasurable and socializing activity, should be considered, because it might contribute to increase adherence to exercise practice and optimize its benefits. The manifestation of sexuality can be potentiated by the combination of music and physical activity, in a situation that naturally propitiates high levels of well-being hormones, such as endorphins6,15. Since 2007, in our CPMR programs in the city of Florianopolis, Santa Catarina state, ballroom dancing has been a mean of physical conditioning, with the adoption of various rhythms (forro, bolero, samba, merengue, waltz, rock and roll, and salsa). Rather than teaching the technique, which would require frequent interruptions, we have been aiming at maintaining patients active as long as possible to sustain their target heart rate zone during exercise training. By doing so, we have achieved higher adherence, with a better chronotropic response and arterial blood pressure control, factors widely associated with sexual dysfunction and even cardiovascular outcomes20,21. The advantage of dancing as compared to conventional exercise methods incorporated to CPMR is mainly due to its characteristic of bringing people closer together, both physically and emotionally. In that context, ballroom dancing can be seen as a strategy to concomitantly treat cardiovascular diseases and sexual dysfunction.

Chorein Sensitivity of Actin Polymerization, Cell Shape and Mechanical Stiffness of Vascular Endothelial Cells

Background/Aims: Endothelial cell stiffness plays a key role in endothelium-dependent control of vascular tone and arterial blood pressure. Actin polymerization and distribution of microfilaments is essential for mechanical cell stiffness. Chorein, a protein encoded by the VPS13A gene, defective in chorea-acanthocytosis (ChAc), is involved in neuronal cell survival as well as cortical actin polymerization of erythrocytes and blood platelets. Chorein is expressed in a wide variety of further cells, yet nothing is known about the impact of chorein on cells other than neurons, erythrocytes and platelets. The present study explored whether chorein is expressed in human umbilical vein endothelial cells (HUVECs) and addressed the putative role of chorein in the regulation of cytoskeletal architecture, stiffness and survival of those cells. Methods: In HUVECs with or without silencing of the VPS13A gene, VPS13A mRNA expression was determined utilizing quantitative RT-PCR, cytoskeletal organization visualized by confocal microscopy, G/F actin ratio and phosphorylation status of focal adhesion kinase quantified by western blotting, cell death determined by flow cytometry, mechanical properties studied by atomic force microscopy (AFM) and cell morphology analysed by scanning ion conductance microscopy (SICM). Results: VPS13A mRNA expression was detectable in HUVECs. Silencing of the VPS13A gene attenuated the filamentous actin network, decreased the ratio of soluble G-actin over filamentous F-actin, reduced cell stiffness and changed cell morphology as compared to HUVECs silenced with negative control siRNA. These effects were paralleled by a significant decrease in FAK phosphorylation following VPS13A silencing. Moreover, silencing of the VPS13A gene increased caspase 3 activity and induced necrosis in HUVECs. Conclusions: Chorein is a novel regulator of cytoskeletal architecture, cell shape, mechanical stiffness and survival of vascular endothelial cells.

Elevated local skin temperature impairs cutaneous vasoconstrictor responses to a simulated haemorrhagic challenge while heat stressed

During a simulated haemorrhagic challenge, syncopal symptoms develop sooner when individuals are hyperthermic relative to normothermic. This is due, in part, to a large displacement of blood to the cutaneous circulation during hyperthermia, coupled with inadequate cutaneous vasoconstriction during the hypotensive challenge. The influence of local skin temperature on these cutaneous vasoconstrictor responses is unclear. This project tested the hypothesis that local skin temperature modulates cutaneous vasoconstriction during simulated haemorrhage in hyperthermic humans. Eight healthy participants (four men and four women; 32 ± 7 years old; 75.2 ± 10.8 kg) underwent lower-body negative pressure to presyncope while heat stressed via a water-perfused suit sufficiently to increase core temperature by 1.2 ± 0.2 °C. At forearm skin sites distal to the water-perfused suit, local skin temperature was either 35.2 ± 0.6 (mild heating) or 38.2 ± 0.2 °C (moderate heating) throughout heat stress and lower-body negative pressure, and remained at these temperatures until presyncope. The reduction in cutaneous vascular conductance during the final 90 s of lower-body negative pressure, relative to heat-stress baseline, was greatest at the mildly heated site (-10 ± 15% reduction) relative to the moderately heated site (-2 ± 12%; P = 0.05 for the magnitude of the reduction in cutaneous vascular conductance between sites), because vasoconstriction at the moderately heated site was either absent or negligible. In hyperthermic individuals, the extent of cutaneous vasoconstriction during a simulated haemorrhage can be modulated by local skin temperature. In situations where skin temperature is at least 38 °C, as is the case in soldiers operating in warm climatic conditions, a haemorrhagic insult is unlikely to be accompanied by cutaneous vasoconstriction.

Psychosomatik und arterielle Hypertonie - Love it or leave it?

Over the last two decades modern psychosomatic research has found multiple evidence for an impact of psychosocial factors on the control of arterial blood pressure as well as the development of arterial hypertension. This narrative review focuses first on the current stress concept and factors that influence the degree of blood pressure change following a psychosocial stressor. Second, relevant psychosocial factors associated with blood pressure are presented such as marital status, social support, socioeconomic status and work conditions. In addition, the influence of personality and cognition on blood pressure will be discussed. The second part focuses on the outcome of cognitive-behavioral therapies and relaxation techniques as a means to effectively control blood pressure. In conclusion, there is now good evidence showing that psychosocial factors and stressors may increase blood pressure. The working environment, the socioeconomic status as well as aspects of personality and cognitive factors like rumination may also impact blood pressure with to an extent that is clinically relevant. With respect to therapeutic options, cognitive-behavioral interventions, combined with relaxation techniques all fitting the needs of the individual patient best can offer a clinically meaningful contribution of an effective blood pressure control.

Endogenous hydrogen sulfide is involved in the brain's control of arterial blood pressure

Hydrogen sulfide (H2S) has recently been found to play an important role in the regulation of the circulatory system, however, its effect on the brain's control of arterial blood pressure has not been established yet. In the study we investigated the hemodynamic effects of intracerebroventricular (icv) infusions of S‐adenosyl‐L‐metionine (SAM), an activator of cystathionine betasynthase which produces H2S in the brain. We preformed experiments on freely moving, male, Wistar Kyoto rats. Mean arterial blood pressure (MAP) and heart rate (HR) were recorded at baseline and during icv infusions of SAM. The infusions produced a dose dependent, biphasic response, i.e. moderate hypotension and bradycardia lasting 10–15 min, which were followed by long‐lasting significant increases in MAP and HR. These findings suggest that endogenous H2S in the brain is involved in the neurogenic control of blood pressure, and that the effects of H2S may depend on its concentration and/or the site of its action in the brain. This work was supported by the National Science Center, grant 3G29 and Medical University of Warsaw, grant 1MA/PM11/11.

Reactive oxygen species enter the tug‐of‐war between metabolic vasodilatation and sympathetic vasoconstriction

Reactive oxygen species enter the tug‐of‐war between metabolic vasodilatation and sympathetic vasoconstriction

Essential hypertension – Is erroneous receptor output to blame?

Hypertension is a chronic medical condition in which systemic arterial blood pressure is elevated. About 80–90% of diagnosed hypertension is considered essential (idiopathic), which means there is no obvious cause of the increase in blood pressure. My hypothesis states that part of idiopathic hypertension results from erroneous information that the brain receives from receptors involved in the regulation of arterial blood pressure, i.e. if, despite high systemic blood pressure, the brain receives false “low-arterial pressure input” from cardiovascular receptors. As a result the brain centres which control blood pressure reset and produce an inappropriate output to the effectors (heart, blood vessels, kidneys and glands). The information errors may result from: (i) structural and/or functional impairment of cardiovascular receptors, (ii) changes in cardiovascular receptors activity, which are caused by other factors than changes in blood pressure, and (iii) impaired transmission in afferent fibres. I assume that in contrast to the lack of input from damaged or denervated cardiovascular receptors, an erroneous input will impair the control of arterial blood pressure. This will apply especially to false input which imitates “low-arterial pressure input”. Higher priority of “low-arterial pressure input” over “high-arterial pressure input” or none input may be explained by the evolutionary adaptation, i.e. low blood pressure, mostly due to haemorrhage, used to be a more common condition than high blood pressure and constitute a major threat to humans.

Avaliação de resultados em um serviço de atenção secundária para pacientes com Diabetes mellitus

OBJETIVO: Avaliar o componente resultado em um serviço de atenção secundária a usuários com Diabetes mellitus tipo 2, tomando como indicadores os controles de pressão arterial, hemoglobina glicada e lipoproteína de baixa densidade. MÉTODOS: Estudo do tipo documental e retrospectivo envolvendo a análise desses indicadores, obtidos nos anos entre 2007 e 2009, com base na consulta de 108 prontuários de usuários de um serviço de atenção secundária, realizada na avaliação de cuidados em saúde. RESULTADOS: Os resultados evidenciaram que 30,3% dos usuários alcançaram a meta para a hemoglobina glicada, 48,1%, para a pressão arterial e 42,3%, para a lipoproteína de baixa densidade. CONCLUSÃO: Os dados avaliados foram semelhantes aos encontrados em outras investigações internacionais e nacionais, com grande proporção de usuários com DM2 estudados, apresentando controle dos níveis hemoglobina A1c, PA e LDL-C, aquém do preconizado nos consensos.

The EMILIN/Multimerin Family

Elastin microfibrillar interface proteins (EMILINs) and Multimerins (EMILIN1, EMILIN2, Multimerin1, and Multimerin2) constitute a four member family that in addition to the shared C-terminus gC1q domain typical of the gC1q/TNF superfamily members contain a N-terminus unique cysteine-rich EMI domain. These glycoproteins are homotrimeric and assemble into high molecular weight multimers. They are predominantly expressed in the extracellular matrix and contribute to several cellular functions in part associated with the gC1q domain and in part not yet assigned nor linked to other specific regions of the sequence. Among the latter is the control of arterial blood pressure, the inhibition of Bacillus anthracis cell cytotoxicity, the promotion of cell death, the proangiogenic function, and a role in platelet hemostasis. The focus of this review is to highlight the multiplicity of functions and domains of the EMILIN/Multimerin family with a particular emphasis on the regulatory role played by the ligand–receptor interactions of the gC1q domain. EMILIN1 is the most extensively studied member both from the structural and functional point of view. The structure of the gC1q of EMILIN1 solved by NMR highlights unique characteristics compared to other gC1q domains: it shows a marked decrease of the contact surface of the trimeric assembly and while conserving the jelly-roll topology with two β-sheets of antiparallel strands it presents a nine-stranded β-sandwich fold instead of the usual 10-stranded fold. This is likely due to the insertion of nine residues that disrupt the ordered strand organization and forma a highly dynamic protruding loop. In this loop the residue E933 is the site of interaction between gC1q and the α4β1 and α9β1 integrins, and contrary to integrin occupancy that usually upregulates cell growth, when gC1q is ligated by the integrin the cells reduce their proliferative activity.