Hypertension in Women.

Hypertension is one of the main causes of morbidity and mortality in the human population. Nevertheless, the intricate network of pathophysiological mechanisms that lead to the development of hypertension in women still awaits to be fully understood. From young age to maturity and senescence, the female body transits through different stages, each of them characterized with specific physiological features and disposition to particular pathological conditions, and that is exactly what makes the understanding of the genesis and adequate treatment of hypertension in women so challenging. Clinical and experimental findings emphasize the role of sex hormones, autonomic nervous system, renin-angiotensin-aldosterone system and arterial stiffness in the development of chronically elevated blood pressure in females. The purpose of this review is to briefly summarize the knowledge of the mechanisms and treatment of hypertension in women.

GLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body Inhibition.

BACKGROUND: Aberrant sympathetic nerve activity exacerbates cardiovascular risk in hypertension and diabetes, which are common comorbidities, yet clinically sympathetic nerve activity remains poorly controlled. The hypertensive diabetic state is associated with increased reflex sensitivity and tonic drive from the peripheral chemoreceptors, the cause of which is unknown. We have previously shown hypertension to be critically dependent on the carotid body (CB) input in spontaneously hypertensive rat, a model that also exhibits a number of diabetic traits. CB overstimulation by insulin and leptin has been similarly implicated in the development of increased sympathetic nerve activity in metabolic syndrome and obesity. Thus, we hypothesized that in hypertensive diabetic state (spontaneously hypertensive rat), the CB is sensitized by altered metabolic signaling causing excessive sympathetic activity levels and dysfunctional reflex regulation. METHODS: Using a hypothesis-free RNA-seq approach, we investigated potential molecular targets implicated in energy metabolism mediating CB sensitization and its regulation of sympathetic outflow in experimental hypertension. Identified targets were characterized using molecular and functional techniques assessing peripheral chemoreflex sensitivity in situ and in vivo. RESULTS: We discovered GLP1R (glucagon-like peptide-1 receptor) expression in the CBs of rat and human and showed that its decreased expression is linked to sympathetic hyperactivity in rats with cardiometabolic disease. We demonstrate GLP1R to be localized to CB chemosensory cells, while targeted administration of GLP1R agonist to the CB lowered its basal discharge and attenuated chemoreflex-evoked blood pressure and sympathetic responses. Importantly, hyperglycemia-induced peripheral chemoreflex sensitization and associated basal sympathetic overactivity were abolished by GLP1R activation in the CB suggesting a role in a homeostatic response to high blood glucose. CONCLUSIONS: We show that GLP1 (glucagon-like peptide-1) modulates the peripheral chemoreflex acting on the CB, supporting this organ as a multimodal receptor. Our findings pinpoint CBs as potential targets for ameliorating excessive sympathetic activity using GLP1R agonists in the hypertensive-diabetic condition.

Static magnetic field on behavior, hematological parameters and organ damage in spontaneously hypertensive rats.

Previous studies showed contradictory results of static magnetic field (SMF) influence on behavior, hematological parameters and organ damage. The aim of this study was to investigate influence of subchronic continuous exposure to upward and downward oriented SMF of moderate intensity on behavior, hematological characteristics, heart and kidney tissue of spontaneously hypertensive rats. SH rats exposed to downward oriented SMF demonstrated lack of anxious-like behavior. SMF of either orientation caused decrease in the number of platelets in peripheral blood, granulocytes in the spleen and bone marrow and increase in the number of erythrocytes in the spleen, in both exposed groups. We also demonstrated that spontaneously hypertensive rats exposed to upward oriented SMF exhibited decreased lymphocytes count in blood, decreased bone marrow erythrocytes count and rats exposed to downward oriented SMF had increased lymphocytes count in bone marrow. The results showed adverse effect of differently oriented SMF on hematological parameters of spontaneously hypertensive rats. Also, exposure to different oriented SMF didn't affect their heart and kidney morphological characteristics.

Biogenic amine content during the production and ripening of Sremski kulen, Serbian traditional dry fermented sausage.

Sremski kulen is a wide diameter dry fermented sausage, produced from pork, seasoned with red spicy paprika, stuffed into pork cecum, and preserved by smoking, fermentation and drying. Due to specific ripening process, Sremski kulen is suitable for the accumulation of biogenic amines. Therefore, the aminogenesis was studied in traditionally produced Sremski kulen, taking into account the physicochemical parameters and microbial counts. The content of six biogenic amines (tryptamine, phenylethylamine, tyramine, histamine, putrescine, and cadaverine) was analyzed using high-performance liquid chromatography. The ripening process of Sremski kulen was slow followed by changes in aw and pH value as well as expressed proteolysis. The autochthonous microbiota showed pronounced decarboxylase activity. Tryptamine and phenylethylamine were detected at each examined ripening stage while histamine was not detected until the end of ripening (16.55 ± 2.33 mg/kg). Tyramine, cadaverine, and putrescine content significantly increased during the ripening period (p < .05). In the final product, cadaverine was the dominant biogenic amine (132.40 ± 5.05 mg/kg), followed by tyramine (115.80 ± 15.46 mg/kg) and putrescine (68.55 ± 2.39 mg/kg). Although the long ripening period greatly contributed to the accumulation of biogenic amines in final product, their content are not of concern from product safety aspects, but requires improvement in hygiene of production process.

Cardiovascular variability and ß-ARs gene expression at two stages of doxorubicin - Induced cardiomyopathy.

Using comprehensive analysis of heart rate (HRV) and blood pressure (BPV) short-term variability we estimated the time course of changes of autonomic nervous system remodeling in two stages of doxorubicin-induced cardiomyopathy (DCM). We also investigated the level of gene expression of cardiac ß-1 (ß-1AR) and ß-2 (ß-2AR) adrenoceptors. Experiments were performed in adult male Wistar rats equipped with indwelling catheters for BP recording and blood withdrawal. A 15 mg/kg total cumulative dose of doxorubicin was injected i.p. to rats to induce DCM or saline for control (n=18). Rats were assessed for general toxicity, cardiovascular hemodynamic and echocardiography before treatment (n=6), 35 days (DOX35; n=6) and 70 days (DOX70; n=6) post-treatment. HRV was evaluated by spectral analysis, Poincaré plots, sample and approximate entropy. Expression of ß-1AR and ß-2AR mRNA was evaluated by RT-qPCR. Doxorubicin-treated rats exhibited poor general condition and lower survival than saline-treated rats. In DOX35 rats, there were no echocardiography signs of decompensation, no increase in serum cardiac troponins, but there was an increase of HRV and decrease of HR complexity. In these rats typical microscopic signs of cardiotoxicity were seen along with over-expression of ß-1AR mRNA. 70 days post-treatment echocardiography revealed signs of decompensation and serum cardiac troponin T was increased. At this stage BPV decreased. In conclusion, HRV increase matches transient over-expression of cardiac ß-1AR mRNA in compensate stage of DCM while decompensate stage of DCM is characterized by a decrease of BPV and no changes in ß-1AR and ß-2AR gene expression.

Sudden death: Neurogenic causes, prediction and prevention.

Sudden death is a major health problem all over the world. The most common causes of sudden death are cardiac but there are also other causes such as neurological conditions (stroke, epileptic attacks and brain trauma), drugs, catecholamine toxicity, etc. A common feature of all these diverse pathologies underlying sudden death is the imbalance of the autonomic nervous system control of the cardiovascular system. This paper reviews different pathologies underlying sudden death with emphasis on the autonomic nervous system contribution, possibilities of early diagnosis and prognosis of sudden death using various clinical markers including autonomic markers (heart rate variability and baroreflex sensitivity), present possibilities of management and promising prevention by electrical neuromodulation.

Dependency Structures in Differentially Coded Cardiovascular Time Series.

Objectives. This paper analyses temporal dependency in the time series recorded from aging rats, the healthy ones and those with early developed hypertension. The aim is to explore effects of age and hypertension on mutual sample relationship along the time axis. Methods. A copula method is applied to raw and to differentially coded signals. The latter ones were additionally binary encoded for a joint conditional entropy application. The signals were recorded from freely moving male Wistar rats and from spontaneous hypertensive rats, aged 3 months and 12 months. Results. The highest level of comonotonic behavior of pulse interval with respect to systolic blood pressure is observed at time lags τ = 0, 3, and 4, while a strong counter-monotonic behavior occurs at time lags τ = 1 and 2. Conclusion. Dynamic range of aging rats is considerably reduced in hypertensive groups. Conditional entropy of systolic blood pressure signal, compared to unconditional, shows an increased level of discrepancy, except for a time lag 1, where the equality is preserved in spite of the memory of differential coder. The antiparallel streams play an important role at single beat time lag.

Static magnetic field reduces blood pressure short-term variability and enhances baro-receptor reflex sensitivity in spontaneously hypertensive rats.

PURPOSE: It has been shown that chronic exposure of young spontaneously hypertensive rats (SHR) to static magnetic field (SMF) delays the development of overt hypertension. Therefore the aim of the present work was to investigate the effects of SMF on autonomic cardiovascular control in adult spontaneously hypertensive rats. MATERIALS AND METHODS: Experiments were performed in freely moving spontaneously hypertensive rats equipped with femoral arterial catheter for blood pressure recording. Spontaneously hypertensive rats were exposed for 30 days to upward-oriented SMF (n = 17) or downward-oriented SMF (n = 17) of 16 mT intensity. A control group of spontaneously hypertensive rats (n = 17) was not exposed to SMF. Neurogenic cardiovascular control was evaluated by spectral analysis of arterial blood pressure and heart rate short-term variability and baro-receptor reflex sensitivity using the sequence method. RESULTS: Exposure of spontaneously hypertensive rats to both upward- and downward-oriented SMF significantly reduced arterial blood pressure and enhanced baro-receptor reflex sensitivity. Downward-oriented SMF reduced heart rate, too. SMF of either orientation reduced systolic blood pressure variability in very low frequency domain while downward-oriented SMF also reduced low-frequency and increased high frequency domains. CONCLUSION: It follows that prolonged exposure to SMF is beneficial for neurogenic cardiovascular control in hypertension.

Over-expression of V1A receptors in PVN modulates autonomic cardiovascular control.

The hypothalamic paraventricular nucleus (PVN) is a key integrative site for the neuroendocrine control of the circulation and of the stress response. It is also a major source of the neuropeptide hormone vasopressin (VP), and co-expresses V1a receptors (V1aR). We thus sought to investigate the role of V1aR in PVN in cardiovascular control in response to stress. Experiments were performed in male Wistar rats equipped with radiotelemetric device. The right PVN was transfected with adenoviral vectors (Ads) engineered to over-express V1aR along with an enhanced green fluorescent protein (eGFP) tag. Control groups were PVN transfected with Ads expressing eGFP alone, or wild-type rats (Wt). Rats were recorded with and without selective blockade of V1aR (V1aRX) in PVN under both baseline and stressed conditions. Blood pressure (BP), heart rate (HR), their short-term variabilities, and baroreflex sensitivity (BRS) were evaluated using spectral analysis and the sequence method, respectively. Under baseline physiological conditions,V1aR rats exhibited reduced BRS and a marked increase of BP and HR variability during exposure to stress. These effects were all prevented by V1aRX pretreatment. In Wt rats, V1aRX did not modify cardiovascular parameters under baseline conditions, and prevented BP variability increase by stress. However, V1aRX pretreatment did not modify baroreflex desensitization by stress in either rat strain. It follows that increased expression of V1aR in PVN influences autonomic cardiovascular regulation and demarcates vulnerability to stress. We thus suggest a possible role of hypothalamic V1aR in cardiovascular pathology.

The optimisation of traditional fermentation process of white cabbage (in relation to biogenic amines and polyamines content and microbiological profile).

White cabbage heads cultivar "Futoski" and hybrid "Bravo" were investigated during fermentation process, for 50days, at different temperature regimes (16-18; 18-20; 20-22°C) and salt concentrations 1, 1.5 and 2%. The quantity of biogenic amines (tryptamine, phenylethylamine, putrescine, cadaverine, histamine, serotonine, tyramine, spermidine and spermine), as well as microbiological profile (lactic acid bacteria, total number of microorganisms, yeasts and moulds and Enterobacteriaceae) have been determined during fermentation. The optimum processing conditions were determined by Response Surface Method, coupled with Fuzzy Synthetic Evaluation algorithm. The optimal process parameters, regarding low biogenic amines and polyamines content, for "Futoski" cabbage was: salt concentration of 2%, at 18°C, and for hybrid "Bravo": salt concentration of 1%, at 20°C.

Overexpression of oxytocin receptors in the hypothalamic PVN increases baroreceptor reflex sensitivity and buffers BP variability in conscious rats.

BACKGROUND AND PURPOSE: The paraventricular nucleus (PVN) of the hypothalamus is an important integrative site for neuroendocrine control of the circulation. We investigated the role of oxytocin receptors (OT receptors) in PVN in cardiovascular homeostasis. EXPERIMENTAL APPROACH: Experiments were performed in conscious male Wistar rats equipped with a radiotelemetric device. The PVN was unilaterally co-transfected with an adenoviral vector (Ad), engineered to overexpress OT receptors, and an enhanced green fluorescent protein (eGFP) tag. Control groups: PVN was transfected with an Ad expressing eGFP alone or untransfected, sham rats (Wt). Recordings were obtained without and with selective blockade of OT receptors (OTX), during both baseline and stressful conditions. Baroreceptor reflex sensitivity (BRS) and cardiovascular short-term variability were evaluated using the sequence method and spectral methodology respectively. KEY RESULTS: Under baseline conditions, rats overexpressing OT receptors (OTR) exhibited enhanced BRS and reduced BP variability compared to control groups. Exposure to stress increased BP, BP variability and HR in all rats. In control groups, but not in OTR rats, BRS decreased during stress. Pretreatment of OTR rats with OTX reduced BRS and enhanced BP and HR variability under baseline and stressful conditions. Pretreatment of Wt rats with OTX, reduced BRS and increased BP variability under baseline and stressful conditions, but only increased HR variability during stress. CONCLUSIONS AND IMPLICATIONS: OT receptors in PVN are involved in tonic neural control of BRS and cardiovascular short-term variability. The failure of this mechanism could critically contribute to the loss of autonomic control in cardiovascular disease.

Sensory, physical and chemical characteristics of cooked ham manufactured from rapidly chilled and earlier deboned M. semimembranosus.

Effects of rapid chilling of carcasses (at -31°C in the first 3h of chilling, and then at 2-4°C) and earlier deboning (8h post-mortem), compared to rapid (till 24h post-mortem) and conventional chilling (at 2-4°C, till 24h post-mortem), on quality characteristics of pork M. semimebranosus and cooked ham were investigated. Quality measurements included pH value, colour (CIEL a b values) and total aerobic count of M. semimebranosus, as well as sensory (colour, juiciness, texture, and flavour), physical (pH value, colour - CIEL a b values and texture - Warner-Bratzler shear and penetration forces) and chemical (protein, total fat, and moisture content) characteristics of cooked ham. The cooked ham was manufactured from pieces of M. semimebranosus with ultimate lightness (CIEL value) lower than 50. Rapid chilling and earlier deboning significantly increased quantity of M. semimebranosus desirable for cooked ham manufacturing. Earlier start of pork fabrication did not affect important quality characteristics of cooked ham.