Elevated Arterial Blood Pressure Research Articles

Effects of full-fat dairy products on subclinical vascular function in adults with elevated blood pressure: a randomized clinical trial.

High consumption of low- and non-fat dairy products improves vascular dysfunction associated with elevated arterial blood pressure (BP). Currently, it is unknown if conventional full-fat dairy products improve vascular functions. To determine if adding whole milk and full-fat dairy products to the normal routine diet improves vascular function in adults with elevated BP. Sixty adults (age ± SEM; 58 ± 2 years) with elevated BP (systolic/diastolic; 120-159/ < 99 mmHg) were randomized into a controlled crossover intervention trial consisting of two 4-week dietary periods. The high dairy condition consisted of adding four daily servings of whole milk or full-fat dairy products to the normal diet and eliminated all dairy intake during the control (no dairy) condition. A 2-week washout period separated the dietary conditions. Carotid-femoral pulse wave velocity (cfPWV) did not differ significantly between high dairy (11.3 ± 0.3 versus 10.9 ± 0.3 m/sec) and no dairy conditions (11.2 ± 0.3 versus 11.0 ± 0.3 m/sec). The results were consistent when ultrasound-derived vascular distension measures (arterial compliance, beta-stiffness index, and elastic modulus) were evaluated. Cardiovagal baroreceptor sensitivity (via Valsalva maneuver) demonstrated no significant difference for either dietary condition. Brachial arterial flow-mediated dilation (FMD) did not differ significantly during the high dairy (5.7 ± 0.5 versus 5.4 ± 0.6%) and no dairy conditions (6.5 ± 0.5 versus 5.6 ± 0.6%). The solitary addition of whole milk and full-fat dairy products has no effect on subclinical vascular function in adults with elevated BP.

Age‐Related Changes in Skeletal Muscle and Small Mesenteric Arterial Function in Spontaneously Hypertensive Rats

Essential hypertension is a chronic idiopathic medical condition that is characterized by elevated arterial blood pressure and is associated with increased risk of cardiovascular disease. Endothelial dysfunction is associated with increased age and a casual factor for the development of hypertension. Therefore, we hypothesized that endothelial dysfunction would be exacerbated by age to a greater extent in spontaneously hypertensive rats (SHRs) compared to Wistar‐Kyoto rats (WKY) control rats. Vascular function was assessed using pressure myography in skeletal muscle and mesenteric resistance arteries isolated from SHR and WKY across three age groups: young (16–17 weeks, n = 4/group), aged (62–64 weeks, n = 4/group) and old (88–100 weeks, n = 5/group). Phenylephrine‐induced vasoconstriction responses in either of the resistance arteries were not significantly different between WKY and SHR at any of the age groups. Endothelial‐dependent vasodilation in mesenteric arteries was not significantly different between WKY and SHR across age groups either. However, endothelium‐dependent vasodilation in the skeletal muscle resistance arteries was significantly enhanced in the young SHR compared to WKY, but not in the aged or old rats. Moreover, endothelial‐independent vasodilation in mesenteric arteries was significantly enhanced in SHR compared to WKY across all age groups, while this difference was only observed in the skeletal muscle resistance arteries of the young rats. Contrary to our hypothesis, these data suggest that endothelial dysfunction is not exacerbated by age in the resistance arteries of SHR.Support or Funding InformationResearch support: National Institute of Health grants: R01 HL137769 (JP), R01 HL088105 (LM‐L).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

EXCESSIVE DIETARY SALT PROMOTES AORTIC STIFFNESS IN 2K1C HYPERTENSION

Renal artery stenosis is the most common cause of secondary hypertension. The 2‐kidney‐1‐clip (2K1C) model of renal stenosis is associated with elevated arterial blood pressure (ABP), activation of the sympathetic nervous system, and blunted reno‐renal reflexes and natriuretic responses. Excess dietary salt intake has multiple actions on the cardiovascular system and exacerbates ABP in some models of hypertension. The present study tested the hypothesis that 2K1C mice exhibit salt sensitive hypertension and worsening cardiovascular responses to high salt feeding. Male C57Bl6 mice (8–12 weeks) were fed 0.1% NaCl or 4% NaCl diets and ABP was continuously monitored using telemetry. 2K1C hypertension was produced by placing a 0.5mm length of PTFE tubing around the right renal artery. Baseline 24‐h mean ABP was not different between 0.1% versus 4.0% NaCl fed mice (101±1 vs 99±1 mmHg, respectively; n=8/group). 2K1C significantly increased ABP in both groups; however, 24‐h mean ABP at 3 weeks post‐renal clipping was not different between mice fed 0.1% vs 4.0% NaCl (122±3 vs. 124±6 mmHg, respectively; n=8/group). In addition, renal artery stenosis significantly increased arterial pulse pressure (systolic‐diastolic) in 0.1% NaCl (Day 0: 35±1 vs Day 21: 42±1 mmHg, P&lt;0.05) and 4.0% NaCl (Day 0: 36±1 vs Day 21: 49±3 mmHg, P&lt;0.05). Interestingly, the magnitude of the increase in arterial pulse pressure was significantly greater in mice fed 4.0% vs 0.1% NaCl (Δ14±3 vs Δ7±2 mmHg, P&lt;0.05). This suggests dietary salt intake promotes aortic stiffness in the 2K1C model. To test this, endothelial‐dependent vasodilatory responses were measured using myography in sham and 2K1C mice fed 0.1% and 4.0% NaCl diets for 3 weeks. 4.0% NaCl 2K1C mice exhibited significantly blunted aortic vasodilation responses versus 2K1C mice fed 0.1% NaCl or sham mice fed 0.1% or 4.0% NaCl. These effects were not observed in the mesenteric arteries of the same animal. In vivo, pulse wave velocity (PWV) measurements revealed a significantly higher PWV value in 2K1C mice fed 4.0% NaCl versus 2K1C fed 0.1% NaCl (3.97±0.19; n=7 vs. 3.18±0.19; n=8, P&lt;0.01) or sham fed 0.1% or 4.0% NaCl (3.21±0.19; n=7 vs. 3.01±0.19; n=7). We conclude that high dietary salt does not exaggerate the chronic hypertension in 2K1C mice but produces a specific endothelial‐dependent aortic stiffness.Support or Funding InformationRO1 HL128388This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Renal Sensory Nerves Increase Blood Pressure and Sympathetic Nerve Activity in 2‐Kidney 1‐Clip Hypertensive Mice

Renal denervation lowers arterial blood pressure (ABP) in multiple clinical trials and some experimental models of hypertension. These antihypertensive effects have been attributed to the removal of renal afferent nerves. The purpose of the present study was to determine whether renal sensory nerves contribute to the 2‐Kidney‐1‐Clip (2K1C) model of hypertension. 2K1C hypertension was produced in male C57B16 mice (12–14 weeks, Jackson Laboratories) by placement of a 0.5mm length of PTFE tubing (ID: 0.008” x OD: 0.014”) around the left renal artery. 2K1C mice (n=10) displayed an elevated ABP measured via telemetry (Day 0: 96 ± 1mmHg vs Day 14: 120 ± 3mmHg; P&lt;0.01). Ganglionic blockade with hexamethonium (30mg/kg, ip) produced a greater fall in mean ABP at Day 14 vs Day 0 (Day 0: −35 ± 2mmHg vs Day 14: −57 ± 5mmHg; P&lt;0.01). 2K1C‐clipped kidneys vs 2K1C‐unclipped kidneys had lower mass (105 ± 14mg vs 173 ± 8mg, respectively; P&lt;0.05) and higher mRNA levels of several pro‐inflammatory cytokines (IL1B, IL2, IL10, TNFa; P&lt;0.05). Renal afferent discharge was significantly higher in 2K1C‐clipped kidneys vs 2K1C‐unclipped vs sham mice (2K1C‐clipped: 3.4 ± 0.9 Hz vs 2K1C‐unclipped: 0.7 ± 0.3Hz vs control: 0.3 ± 0.1 Hz, n=6/group; P&lt;0.05). Furthermore, electrical stimulation of renal afferent nerves in control mice (n=6) produced a frequency‐dependent increase in ABP (5Hz: 4 ± 1mmHg, 10Hz: 6 ± 1mmHg, 20Hz: 11 ± 2mmHg; P&lt;0.05). These responses were eliminated after ganglionic blockade with 5mg/kg chlorisondamine (5Hz: 1 ± 1mmHg, 10Hz: 1 ± 1mmHg, 20Hz: 1 ± 1mmHg, n=4/group; P&lt;0.05). Stimulus‐triggered averaging of SNA during stimulation of renal afferent nerves (1 Hz, 200uA) revealed significant (P&lt;0.05, n=4/group) increases in splanchnic (179 ± 11%), renal (195 ± 15%), and lumbar (167 ± 9%) SNA. Interestingly, the latency to the peak SNA (142 ± 10ms) suggests supraspinal pathways mediate the sympathoexcitatory response. Finally, both total renal denervation (10% phenol) or selective denervation of renal afferent nerves (periaxonal application of 33mM capsaicin) at time of clipping resulted in lower ABP than 2K1C mice at Day 14 (2K1C: 120 ± 3mmHg, phenol: 106 ± 3mmHg, capsaicin: 108 ± 3mmHg, n=6–10/group; P&lt;0.05). These findings suggest 2K1C hypertension depends on renal sensory nerves and elevated SNA via supraspinal pathways.Support or Funding InformationNIH grant HL113270, AHA Undergraduate Research FellowshipThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

PULSATILE DRUG DELIVERY SYSTEMS: A CASE OF BETA-BLOCKERS

The diseases involve heart and blood vessels are classified under cardiovascular diseases. Hypertension (HTN) is a disorder of the CV system characterized by elevated arterial blood pressure. Pulsatile drug delivery systems are on highlight today. This is due to their distinct advantage of releasing drug as the circadian rhythm of the disease. The beta-blockers are first-line therapy for the HTN. Hence, researches related to such modified formulations of these drugs are of need to increase the patient compliance and convenience. This review describes the various such systems published in literature. This also includes a brief description about circadian rhythm and beta-blockers. The researchers involved in the development of modified release formulations are the main target audience for this review.

Cyclosporine Metabolites' Metabolic Ratios May Be Markers of Cardiovascular Disease in Kidney Transplant Recipients Treated with Cyclosporine A-Based Immunosuppression Regimens.

Cardiovascular disease (CVD) remains one of the primary causes of death after kidney transplantation (KTX). Cyclosporine (CsA) metabolites may play a role in CVD. Metabolic ratio (MR) may be considered a measure of intra-individual differences of CsA metabolism. The study was aimed at analysis of associations of CVD with indices of CsA metabolism: MRs and dose-adjusted CsA concentrations (C/D and C/D/kg). The study was performed in the Department of Immunology, Transplant Medicine, and Internal Diseases of the Medical University of Warsaw and involved 102 KTX recipients. Whole blood concentrations of cyclosporine A, AM1, AM9, AM4N, demethylcarboxylated (dMC-CsA), dihydroxylated (DiH-CsA), trihydroxylated (TriH-CsA) cyclosporine metabolites were determined by liquid chromatography coupled with tandem mass spectrometry. Lower AM9/CsA were observed in diabetics. Patients with coronary disease and/or myocardial infarction had lower dMC-CsA/CsA and higher AM4N/CsA. Supraventricular arrhythmia (SVA) was associated with higher AM1/CsA and AM4N/CsA. Hypertriglyceridemia (hTG) was associated with lower AM9/CsA, higher C/D and C/D/kg. Decrease of AM9/CsA and AM4N and higher D/C were associated with overweight/obesity. Systolic blood pressure (BP) positively correlated with dMC-CsA/CsA and negatively with C/D/kg. Diastolic BP correlated positively with AM1/CsA, dMC-CsA/CsA, DiH-CsA/CsA and TriH-CsA/CsA. We have demonstrated the association of coronary disease/myocardial infarction, SVA, hTG, overweight/obesity and elevated arterial BP with higher MRs of AM1, AM4N, dMC-CsA, DiH-CsA and TriH-CsA, and lower MRs of AM9, which may indicate deleterious and favourable effects of individual CsA metabolites on cardiovascular system and suggest engagement of specific enzymatic pathways.

Defective Choroidal Blood Flow Baroregulation and Retinal Dysfunction and Pathology Following Sympathetic Denervation of Choroid.

PurposeWe sought to determine if sympathetic denervation of choroid impairs choroidal blood flow (ChBF) regulation and harms retina.MethodsRats received bilateral superior cervical ganglionectomy (SCGx), which depleted choroid of sympathetic but not parasympathetic innervation. The flash-evoked scotopic ERG and visual acuity were measured 2 to 3 months after SCGx, and vasoconstrictive ChBF baroregulation during high systemic arterial blood pressure (ABP) induced by LNAME was assessed by laser Doppler flowmetry (LDF). Eyes were harvested for histologic evaluation.ResultsChBF increased in parallel with ABP in SCGx rats over an ABP range of 90% to 140% of baseline ABP, while in sham rats ChBF remained stable and uncorrelated with ABP. ERG a- and b-wave latencies and amplitudes, and visual acuity were significantly reduced after SCGx. In SCGx retina, Müller cell GFAP immunolabeling was upregulated 2.5-fold, and Iba1+ microglia were increased 3-fold. Dopaminergic amacrine cell fibers in inner plexiform layer were reduced in SCGx rats, and photoreceptors were slightly depleted. Functional deficits and pathology were correlated with impairments in sympathetic regulation of ChBF.ConclusionsThese studies indicate that sympathetic denervation of choroid impairs ChBF baroregulation during elevated ABP, leading to choroidal overperfusion. This defect in ChBF regulation is associated with impaired retinal function and retinal pathology. As sympathetic ChBF baroregulatory defects have been observed in young individuals with complement factor H (CFH) polymorphisms associated with risk for AMD, our results suggest these defects may harm retina, perhaps contributing to AMD pathogenesis.

Abstract 039: Differential Expression of miR-146b-5p Modulates Sex-Specific Cardiac Phenotypes in a Rat Model of Chronic Kidney Disease

Type 4 cardiorenal syndrome is a complex disorder in which primary chronic kidney disease (CKD) contributes to secondary cardiovascular disease (CVD). Although the pathological link between the kidney and heart are well-characterized, the molecular switches which drive cardiac pathology are not well understood. miRNAs have the potential to be master regulators of cellular signaling networks through modulation of RNA and protein expression profiles and have been shown to be important in both cardiovascular health and disease. Previous work in our laboratory identified a significant increase of miR-146b-5p expression in both the heart and the kidney in a 5/6 nephrectomy (5/6Nx) model of CKD in the Sprague-Dawley rat. To evaluate how miR-146b-5p is involved with pathological changes in the heart following 5/6Nx, echocardiography, blood pressure and left ventricle (LV) pressure-volume analyses were performed on male and female wild-type (WT) and miR-146b-5p null mutant (146b -/- ) rats for seven weeks following 5/6Nx or sham surgery. Structural analysis of the heart revealed that male and female rats exhibited significant hypertrophy of the LV wall in both the WT (+21% [1.50 vs. 1.24g] and +24% [1.00 vs. 0.81g] vs. sham, respectively; p&lt;0.001) and 146b -/- (+17% [1.36 vs. 1.17g] and +26% [1.03 vs. 0.82g] vs. sham, respectively; p&lt;0.001) genotypes. Furthermore, dilation of the LV chamber was observed in WT male (+9% LVIDd [9.45 vs. 8.67mm] vs. sham; p=0.032) and female (+29% LVIDd [9.39 vs. 7.30mm] and +36% LVIDs [5.80 vs. 4.86mm] vs. sham; p&lt;0.005) rats 7 weeks post-5/6Nx. However, LV dilation was attenuated in 146b -/- females (-18% LVIDd [8.18 vs. 9.39mm] and -26% LVIDs [4.88 vs. 5.80mm] vs. WT; p=0.07) but not in 146b -/- males. Functionally, LV pressure-volume analysis revealed 146b -/- females exhibit an increase in stroke work (+59% vs. sham; p=0.063) and a significantly elevated mean arterial blood pressure (+23mmHg vs. sham; p=0.02). These alterations in cardiovascular function are not observed in miR-146b -/- males. Taken together, these data suggest 146b -/- female rats may be resistant to eccentric dilation despite increased afterload and highlight the sex-specific modulation of cardiorenal phenotypes by miR-146b-5p following 5/6Nx.

Abstract 081: Renal Sensory Nerves Increase Blood Pressure and Sympathetic Nerve Activity in 2-Kidney 1-Clip Hypertensive Mice

Renal denervation lowers arterial blood pressure (ABP) in multiple clinical trials and some experimental models of hypertension. These antihypertensive effects have been attributed to the removal of renal afferent nerves. The purpose of the present study was to determine whether renal sensory nerves contributed to the 2-Kidney-1-Clip (2K1C) model of hypertension. 2K1C hypertension was produced in male C57Bl6 mice (12-14 weeks, Jackson Laboratories) by placement of a 0.5mm length of PTFE tubing (ID: 0.008” x OD: 0.014”) around the left renal artery. 2K1C mice (n=6) displayed an elevated ABP measured via telemetry (Day 0: 96±4mmHg vs Day 14: 115±3mmHg, P&lt;0.05). Ganglionic blockade with hexamethonium (30mg/kg, ip) produced a greater fall in mean ABP at Day 14 vs Day 0 (Day 0: -38±4mmHg vs Day 14: -51±4mmHg, P&lt;0.05). Ipsilateral vs contralateral kidneys of 2K1C mice had lower mass (0.072±0.01g vs 0.163±0.02g, respectively; P&lt;0.05) and higher mRNA levels of several pro-inflammatory cytokines (IL1B, IL2, IL10, TNFa; P&lt;0.05). Both total renal denervation (10% phenol) or selective denervation of renal afferent nerves (periaxonal application of 33mM capsaicin) at time of clipping resulted in a lower ABP than 2K1C mice at Day 14 (2K1C: 115±3mmHg, phenol: 104±2mmHg, capsaicin: 105±3mmHg; P&lt;0.05). Direct recording of renal afferent nerve activity showed significantly greater discharge in 2K1C versus control mice (control: 2.2±1.3Hz vs 2K1C: 61±12Hz, n=3/group; P&lt;0.05). Furthermore, electrical stimulation of renal afferent nerves in control mice produced a frequency-dependent increase in ABP (5Hz: 3±1mmHg, 10Hz: 7±1mmHg, 20Hz: 12±2mmHg, n=4/group; P&lt;0.05). These responses were eliminated after ganglionic blockade with 5mg/kg chlorisondamine (5Hz: 1±1mmHg, 10Hz: 1±1mmHg, 20Hz: 1±1mmHg; P&lt;0.05). Stimulus-triggered averaging of SNA during stimulation of renal afferent nerves (1 Hz, 200uA) revealed significant (P&lt;0.05, n=4/group) increases in splanchnic (221±28%), renal (195+15%), and lumbar (234±32%) SNA. Interestingly, the latency to the peak SNA (142±10ms) suggests supraspinal pathways mediate the sympathoexcitatory response. These findings suggest 2K1C hypertension depends on renal sensory nerves and elevated SNA via supraspinal pathways.

The Influence of the North Atlantic Oscillation Index on Emergency Ambulance Calls for Elevated Arterial Blood Pressure

The North Atlantic Oscillation (NAO) is the most prominent pattern of atmospheric variability over the middle and high latitudes of the Northern Hemisphere, especially during the cold season. It is found that “weather types” are associated with human health. It is possible that variations in NAO indices (NAOI) had additional impact on human health. We investigated the association between daily emergency ambulance calls (EACs) for exacerbation of essential hypertension and the NAOI by using Poisson regression, adjusting for season, weather variables and exposure to CO, particulate matter and ozone. An increased risk of EACs was associated with NAOI &lt; −0.5 (Rate Ratio (RR) = 1.07, p = 0.013) and NAOI &gt; 0.5 (RR = 1.06, p = 0.004) with a lag of 2 days as compared to −0.5 ≤ NAOI ≤ 0.5. The impact of NAOI &gt; 0.5 was stronger during November-March (RR = 1.10, lag = 0, p = 0.026). No significant associations were found between the NAOI and EACs during 8:00–13:59. An elevated risk was associated during 14:00–21:59 with NAOI &lt; −0.5 (RR = 1.09, p = 0.003) and NAOI &gt; 0.5 (RR = 1.09, p = 0.019) and during 22:00–7:59 with NAOI &lt; −0.5 (RR = 1.12, lag = 1, p = 0.001). The non-linear associations were found between the NAO and EACs. The different impact of the NAO was found during the periods November–March and April–October. The impact of the NAOI was not identical for different times of the day.

Carotid Body Ablation: a New Target to Address Central Autonomic Dysfunction.

An abnormal heightened carotid body (CB) chemoreflex, which produces autonomic dysfunction and sympathetic overactivation, is the common hallmark of obstructive sleep apnea (OSA), resistant hypertension, systolic heart failure (HF), and cardiometabolic diseases. Accordingly, it has been proposed that the elimination of the CB chemosensory input to the brainstem may reduce the autonomic and cardiorespiratory alterations in sympathetic-associated diseases in humans. A growing body of evidence obtained in preclinical animal models support that an enhanced CB discharge produces sympathetic hyperactivity, baroreflex sensitivity and heart rate variability impairment, breathing instability, hypertension, and insulin resistance. The elimination CB chemosensory input reduces the sympathetic hyperactivity, the elevated arterial blood pressure in OSA and hypertensive models, abolishes breathing instability and improves animal survival in HF models, and restores insulin tolerance in metabolic models. These results highlight the role played by the enhanced CB drive in the progression of sympathetic-related diseases and support the proposal that the surgical ablation of the CB is useful to restore the autonomic balance and normal cardiorespiratory function in humans. Accordingly, the CB ablation has been used in pilot human studies as a therapeutic treatment for resistant hypertension and HF-induced sympathetic hyperactivity. In this review, I will discuss the supporting evidence for a crucial contribution of the CB in the central autonomic dysfunction and the pros and cons of the CB ablation as a therapy to revert autonomic overactivation. The CB ablation could be a useful method to reverse the enhanced chemoreflex in HF and severe hypertension, but caution is required before extensive use of bilateral CB ablation, which abolished ventilatory responses to hypoxia and may impair baroreceptor function.

Elevated arterial blood pressure after superior cavo-pulmonary anastomosis is associated with elevated pulmonary artery pressure and cerebrovascular dysautoregulation.

Elevated arterial blood pressure (ABP) is common after superior bidirectional cavopulmonary anastomosis (BCPA). The effects of elevated ABP after BCPA on cerebrovascular hemodynamics are unknown. We sought to determine the relationship between elevated ABP and cerebrovascular autoregulation after BCPA. Prospective, observational study on infants with single-ventricle physiology after BCPA surgery. Continuous recordings of mean ABP, mean cavopulmonary artery pressure (PAP), near-infrared spectroscopy measures of cerebral oximetry (regional cerebral oxygen saturation (rSO2)), and relative cerebral blood volume index were obtained from admission to extubation. Autoregulation was measured as hemoglobin volume index (HVx). Physiologic variables, including the HVx, were tested for variance across ABP. Sixteen subjects were included in the study. Elevated ABP post-BCPA was associated with both, elevated PAP (P<0.0001) and positive HVx (dysautoregulation; P<0.0001). No association was observed between ABP and alterations in rSO2. Using piecewise regression, the relationship of PAP to ABP demonstrated a breakpoint at 68 mm Hg (interquartile range (IQR) 62-70 mm Hg). Curve fit of HVx as a function of ABP identified optimal ABP supporting robust autoregulation at a median ABP of 55 mm Hg (IQR 51-64 mm Hg). Elevated ABP post-BCPA is associated with cerebrovascular dysautoregulation, and elevated PAP. The effects, of prolonged dysautoregulation within this population, require further study.

Short-Term Changes in Weather and Space Weather Conditions and Emergency Ambulance Calls for Elevated Arterial Blood Pressure

Circadian rhythm influences the physiology of the cardiovascular system, inducing diurnal variation of blood pressure. We investigated the association between daily emergency ambulance calls (EACs) for elevated arterial blood pressure during the time intervals of 8:00–13:59, 14:00–21:59, and 22:00–7:59 and weekly fluctuations of air temperature (T), barometric pressure, relative humidity, wind speed, geomagnetic activity (GMA), and high-speed solar wind (HSSW). We used the Poisson regression to explore the association between the risk of EACs and weather variables, adjusting for seasonality and exposure to CO, PM10, and ozone. An increase of 10 °C when T &gt; 1 °C on the day of the call was associated with a decrease in the risk of EACs during the time periods of 14:00–21:59 (RR (rate ratio) = 0.78; p &lt; 0.001) and 22:00–7:59 (RR = 0.88; p = 0.35). During the time period of 8:00–13:59, the risk of EACs was positively associated with T above 1 °C with a lag of 5–7 days (RR = 1.18; p = 0.03). An elevated risk was associated during 8:00–13:59 with active-stormy GMA (RR = 1.22; p = 0.003); during 14:00–21:59 with very low GMA (RR = 1.07; p = 0.008) and HSSW (RR = 1.17; p = 0.014); and during 22:00–7:59 with HSSW occurring after active-stormy days (RR = 1.32; p = 0.019). The associations of environmental variables with the exacerbation of essential hypertension may be analyzed depending on the time of the event.

Cerebral Haemodynamics: Effects of Systemic Arterial Pulsatile Function and Hypertension.

Concepts of pulsatile arterial haemodynamics, including relationships between oscillatory blood pressure and flow in systemic arteries, arterial stiffness and wave propagation phenomena have provided basic understanding of underlying haemodynamic mechanisms associated with elevated arterial blood pressure as a major factor of cardiovascular risk, particularly the deleterious effects of isolated systolic hypertension in the elderly. This topical review assesses the effects of pulsatility of blood pressure and flow in the systemic arteries on the brain. The review builds on the emerging notion of the "pulsating brain", taking into account the high throughput of blood flow in the cerebral circulation in the presence of mechanisms involved in ensuring efficient and regulated cerebral perfusion. Recent studies have provided evidence of the relevance of pulsatility and hypertension in the following areas: (i) pressure and flow pulsatility and regulation of cerebral blood flow, (ii) cerebral and systemic haemodynamics, hypertension and brain pathologies (cognitive impairment, dementia, Alzheimer's disease), (iii) stroke and cerebral small vessel disease, (iv) cerebral haemodynamics and noninvasive estimation of cerebral vascular impedance, (v) cerebral and systemic pulsatile haemodynamics and intracranial pressure, (iv) response of brain endothelial cells to cyclic mechanical stretch and increase in amyloid burden. Studies to date, producing increasing epidemiological, clinical and experimental evidence, suggest a potentially significant role of systemic haemodynamic pulsatility on structure and function of the brain.

Nonmuscle Myosin Light Chain Kinase: A Key Player in Intermittent Hypoxia-Induced Vascular Alterations.

BackgroundObstructive sleep apnea is characterized by repetitive pharyngeal collapses during sleep, leading to intermittent hypoxia (IH), the main contributor of obstructive sleep apnea–related cardiovascular morbidity. In patients and rodents with obstructive sleep apnea exposed to IH, vascular inflammation and remodeling, endothelial dysfunction, and circulating inflammatory markers are linked with IH severity. The nonmuscle myosin light chain kinase (nmMLCK) isoform contributes to vascular inflammation and oxidative stress in different cardiovascular and inflammatory diseases. Thus, in the present study, we hypothesized that nmMLCK plays a key role in the IH‐induced vascular dysfunctions and inflammatory remodeling.Methods and ResultsTwelve‐week‐old nmMLCK +/+ or nmMLCK −/− mice were exposed to 14‐day IH or normoxia. IH was associated with functional alterations characterized by an elevation of arterial blood pressure and stiffness and perturbations of NO signaling. IH caused endothelial barrier dysfunction (ie, reduced transendothelial resistance in vitro) and induced vascular oxidative stress associated with an inflammatory remodeling, characterized by an increased intima‐media thickness and an increased expression and activity of inflammatory markers, such as interferon‐γ and nuclear factor‐κB, in the vascular wall. Interestingly, nmMLCK deletion prevented all IH‐induced functional and structural alterations, including the restoration of NO signaling, correction of endothelial barrier integrity, and reduction of both oxidative stress and associated inflammatory response.ConclusionsnmMLCK is a key mechanism in IH‐induced vascular oxidative stress and inflammation and both functional and structural remodeling.

The mechanism effects of CD4+ CD25+ Foxp3+ regulatory T cells in essential hypertension

Primary hypertension is a kind of cardiovascular syndrome which main clinical manifestation is elevated systemic arterial blood pressure, and it's exact pathogenesis remains unclear. Regulatory T cells are a group of T cell subgroups with immunosuppressive and immunocompromised functions, they play an irreplaceable role in the process of immune suppression and immune tolerance. Recently many studies have showed that hypertension is often accompanied by abnormal immune functions. To search the mechanism of action of regulatory T cells in the development of hypertension is significance to prevent and treat hypertension. Key words: Hypertension/IM; T-lymphocytes, regulatory; CD4-positive T-lymphocytes; Review

Lupus in fabula - hipertenzija mlađeg muškarca i sistemski lupus eritematozus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women during the reproductive period (the ratio of female to male is 9 to 1). Although SLE can affect any organ, glomerulonephritis mediated by immune complexes lead to a sudden deterioration of the disease. The literature data indicate the role of chronic inflammation in the pathogenesis of arterial hypertension (HTA) in patients with SLE. This is a case study of a young man with a newly diagnosed HTA, with lupus nephritis behind. The data were obtained retrospectively, by analyzing the patient's medical record. A 40-year-old patient, with a two-year history of irregular and unsuccessful treatment of HTA with ACE inhibitor, saw his doctor for frequent headaches and elevated arterial blood pressure (TA) during self-measurement. By physical examination an auscultatively accelerated cardiac action was found, TA was 170/100 mmHg, and the ECG registered sinus tachycardia (about 100 bpm), while the rest of the finding was neat. Anamnestic data revealed that patient was recreational athlete, a non-smoker, and there was no positive family history of cardiovascular disease. Laboratory report of blood and urine was without significant deviation. Beta blocker and thiazide diuretic were used in the therapy. A month later lower leg edema appeared, followed by highly elevated TA values (up to 200/110 mmHg) and maculopapular rash. The patient was sent to the internist, and then hospitalized at the department of allergology. During the hospitalization, additional diagnostics was made. Laboratory finding reported sudden renal impairment and anemia (creatinine 144 mmol/L, urea 15.8 mmol/L, proteinuria 9.4 g/day, hemoglobin 106 g/L), and immunological analyzes indicated the positivity of SLE specific antibodies (ANA 1:160; anti-dsDNA 1:320). The patient was moved into the nephrology department where the treatment was initiated by the bolus of methylprednisolone (3x500mg). Under the control of ultrasound, a biopsy of the kidneys was performed, and the pathohistological finding showed lupus nephritis of class IV-G (A / C), activity index 17 and chronicity index 4, of the total of eight analyzed glomeruli one was globally sclerotic and in 3 glomeruli found crescent. Cyclophosphamide bolus therapy was started, and patient was released in a well general condition with prescribed corticosteroid and antihypertensive therapy - ACE inhibitor, calcium-channel blocker, Henle's loop diuretic, and beta blocker. Understanding the pathophysiology of HTA in this chronic autoimmune disease is of great clinical significance for patients suffering from SLE, as the cardiovascular disease is still the main cause of mortality with these patients.

Feohromocitom kao uzrok sekundarne arterijske hipertenzije

Pheohromocytoma is a catecholamine-secreting tumor and it is most commonly found in the adrenal glands, but can also be found outside of them. Generally benign, it has malignant potential in about 10% of all cases. Represents a rare cause of secondary arterial hypertension (HTA). It occurs in 0.1% of all HTA cases. A case study of a young man with secondary HTA caused by pheochromocytoma. Retrospective analysis of the patient's medical record was done. A 37-year-old patient reported to the doctor because of occasionally elevated arterial blood pressure (TA) levels in self-measurement, followed by headache, redness in the face, frequent epistaxis and weight loss. From anamnestic data we found a recreational athlete, a non-smoker, and no hereditary risk factors for cardiovascular disease. The physical finding at the first examination is neat, except for the TA level of 210/110 mmHg. The ECG registered 108 bpm sinus tachycardia. TA was ambulantory regulated by oral therapy, and the patient was proceed to laboratory analysis of blood and urine and an echosonographic examination of the abdomen. On the control check TA was 180/95 mmHg, laboratory findings in the reference range, other than glycemia of 11.3 mmol/L. Abdominal echosonography revealed tumor mass in the area of the right adrenal lodge. After repeated hyperglycemia and HbA1c elevated level oral antidiabetics and antihypertensive therapy by ACE inhibitor were prescribed. Patient was sent to the endocrine surgeon due to described tumor mass. MDCT scan and MRI finding of the adrenal loudge confirm the presence of tumor mass in the right adrenal gland. Additional laboratory findings showed elevated levels of metanefrin and chromogranin A in plasma, and a higher levels of degradation products of catecholamines (vanilmendelic acid and metanefrine) in 24h-urine was detected. Based on clinical phenomenology and the findings of additional diagnostic procedures, a suspicion of pheochromocytoma was raised and surgical treatment was indicated. The tumor mass was operationally removed. Pathohistological findings confirmed the diagnosis. The patient was released in good general condition with prescribed antihypertensive and antidiabetic therapy. In the period of one-year postoperative follow-up, the primary disease remained without relapse, TA was adequately medicamenotous regulated, and laboratory findings was within the reference range. In the etiological consideration of elevated TA values in younger individuals it is also important to keep in mind the rare causes such as pheochromocytoma. With timely diagnosis and adequate treatment, a patient's cure can be achieved, while unrecognized cases can result in a fatal outcome.

Reversible brain lesion following growth hormone replacement therapy in an adolescent

A 12.6-year-old girl presented with a 2-month history of headache, recurrent vomiting and 5 kg weight loss. She had been receiving recombinant human growth hormone (rhGH) replacement therapy at a...

Continuous Cardiac Autonomic and Hemodynamic Responses to Isometric Exercise.

Elevated arterial blood pressure (BP) is associated with autonomic dysfunction and impaired hemodynamic control mechanisms. Isometric exercise (IE) training has been demonstrated effective at reducing BP; however, the continuous cardiovascular responses during IE are underinvestigated. We hypothesized that reflex autonomic cardiovascular control is an important mediator in reducing BP. To test our hypothesis, we investigated continuous cardiac autonomic modulation and baroreceptor reflex sensitivity (BRS) in response to IE. Twenty-five prehypertensive participants performed a single IE wall squat training session. Total power spectral density (PSD) of HR variability (HRV) and associated low-frequency (LF) and high-frequency (HF) power spectral components were recorded in absolute (ms) and normalized units (nu) before, during, and after an IE session. HR was recorded via electrocardiography and BRS via the sequence method. Continuous BP was recorded via the vascular unloading technique and stroke volume via impedance cardiography. Total peripheral resistance was calculated according to Ohm's law. During IE, there were significant reductions in HRV (P < 0.05) and BRS (P < 0.05) and significant increases in HR (P < 0.001), systolic, diastolic, and mean BP (all P < 0.001). In recovery from IE, HRV (P < 0.001), HFnu (P < 0.001), and BRS (P < 0.001) significantly increased with a significant decrease in LFnu (P < 0.001) and LF:HF ratio (P < 0.001), indicative of predominant parasympathetic over sympathetic activity. This autonomic response was associated with a significant reduction in systolic (23.2 ± 18.1 mm Hg, P < 0.001), diastolic (18.7 ± 16.9 mm Hg, P < 0.001), and mean (15.8 ± 15.5 mm Hg, P < 0.001) BP, below baseline and a significant reduction in total peripheral resistance (P < 0.001). A single IE session is associated with improved cardiac autonomic modulation and hemodynamic cardiovascular control in prehypertensive males. These acute responses may be mechanistically linked to the chronic reductions in resting BP reported after IE training interventions.