Rise In BP Research Articles

Effect of CPAP Withdrawal on BP in OSA: Data from Three Randomized Controlled Trials

Based on meta-analyses, the BP-lowering effect of CPAP therapy in patients with OSA is reported to be approximately 2 to 3mmHg. This figure is derived from heterogeneous trials, which are often limited by poor CPAP adherence, and thus the treatment effect may possibly be underestimated. We analyzed morning BP data from three randomized controlled CPAP withdrawal trials, which included only patients with optimal CPAP compliance. Within the three trials, 149 patients with OSA who were receiving CPAP were randomized to continue therapeutic CPAP (n= 65) or to withdraw CPAP (n= 84) for 2weeks. Morning BP was measured at home before and after sleep studies in the hospital. CPAP withdrawal was associated with a return of OSA (apnea-hypopnea index [AHI] at a baseline of 2.8/h and at follow-up of 33.2/h). Office systolic BP (SBP) increased in the CPAP withdrawal group compared with the CPAP continuation group by+5.4mmHg (95%CI, 1.8-8.9mmHg; P= .003) and in the home SBP group by+9.0mmHg (95%CI, 5.7-12.3mmHg; P< .001). Office diastolic BP (DBP) increased by+5.0mmHg (95%CI, 2.7-7.3mmHg; P< .001), and home DBP increased by+7.8mmHg (95%CI,5.6-10.4mmHg; P< .001). AHI, baseline home SBP, use of statin drugs, sex, and the number of antihypertensive drugs prescribed were all independently associated with SBP change in multivariate analysis, controlling for age, BMI, smoking status, diabetes, and sleepiness. CPAP withdrawal results in a clinically relevant increase in BP, which is considerably higher than in conventional CPAP trials; it is also underestimated when office BP is used. Greater OSA severity is associated with a higher BP rise in response to CPAP withdrawal. ClinicalTrials.gov; No.: NCT01332175 and NCT01797653) URL: www.clinicaltrials.gov and ISRCTN registry (ISRCTN 93153804) URL: http://www.isrctn.com/.

Effect of salt intake on beat-to-beat blood pressure nonlinear dynamics and entropy in salt-sensitive versus salt-protected rats

Blood pressure exhibits substantial short‐ and long‐term variability (BPV). We assessed the hypothesis that the complexity of beat‐to‐beat BPV will be differentially altered in salt‐sensitive hypertensive Dahl rats (SS) versus rats protected from salt‐induced hypertension (SSBN13) maintained on high‐salt versus low‐salt diet. Beat‐to‐beat systolic and diastolic BP series from nine SS and six SSBN13 rats (http://www.physionet.org) were analyzed following 9 weeks on low salt and repeated after 2 weeks on high salt. BP complexity was quantified by detrended fluctuation analysis (DFA), short‐ and long‐range scaling exponents (α S and α L), sample entropy (SampEn), and traditional standard deviation (SD) and coefficient of variation (CV(%)). Mean systolic and diastolic BP increased on high‐salt diet (P < 0.01) particularly for SS rats. SD and CV(%) were similar across groups irrespective of diet. Salt‐sensitive and ‐protected rats exhibited similar complexity indices on low‐salt diet. On high salt, (1) SS rats showed increased scaling exponents or smoother, systolic (P = 0.007 [α L]) and diastolic (P = 0.008 [α L]) BP series; (2) salt‐protected rats showed lower SampEn (less complex) systolic and diastolic BP (P = 0.046); and (3) compared to protected SSBN13 rats, SS showed higher α L for systolic (P = 0.01) and diastolic (P = 0.005) BP. Hypertensive SS rats are more susceptible to high salt with a greater rise in mean BP and reduced complexity. Comparable mean pressures in sensitive and protective rats when on low‐salt diet coupled with similar BPV dynamics suggest a protective role of low‐salt intake in hypertensive rats. This effect likely reflects better coupling of biologic oscillators.

Topochemistry of Internuclear and Intranuclear Interneurons of the Vasomotor Area in the Medulla Oblongata of Hypertensive Rats.

Immunohistochemical examination with the antiserum against neuronal NO synthase and cystathionine β-synthase was used to study the following two pools of interneurons in Wistar rats at various periods after the development of renovascular hypertension: intranuclear interneurons (lying in the projection of the solitary nucleus, reticular gigantocellular nucleus, and parvocellular nucleus) and 2 groups of internuclear interneurons (small interneurons, area 50-300 μ(2); and large interneurons, area above 350 μ(2)). Intranuclear and internuclear interneurons probably play a role in the central mechanisms of hemodynamics regulation. These interneurons differ by not only in topochemical parameters, but also functional properties (different resistances to BP changes). Intranuclear interneurons are characterized by high sensitivity of the gas transmitter systems to a continuous increase in BP, which results in remodeling and dysfunction of the bulbar part of the cardiovascular center. Large internuclear interneurons demonstrate a strong reaction to BP rise, which confirms their involvement into hemodynamics regulation. By contrast, small internuclear interneurons retain their characteristics in arterial hypertension and probably perform an integrative function.

Influence of the hospital environment and presence of the physician on the white-coat effect.

To determine the separate contribution of the physician and the hospital environment to differences between home (HBP) and office BP (OBP). For 3 consecutive days, 65 hypertensive patients measured their HBP. OBP was determined with the same device by the physician. A higher OBP than HBP was regarded as white-coat effect (WCE), whereas lower OBP than HBP was regarded masked effect. OBP was measured automatically before, during and after the presence of the physician. The physician effect was the BP rise caused by the entrance of physician. The WCE minus the physician effect was regarded the hospital's contribution to the BP differences (hospital effect). We assessed the magnitudes of the hospital effect and the physician effect in determining the WCE. Furthermore, we assessed the correlation of these BP phenomena with each other, and with clinical variables. The WCE consisted of 4.6/-1.7 ± 9.9/10.9 mmHg hospital effect and of 4.4/3.4 ± 6.6/3.3 mmHg PE. The masked effect consisted of a substantially larger hospital effect (19.6/9.4 ± 12.7/9.5 mmHg) than physician effect (4.6/3.0 ± 6.4/3.9 mmHg). Physician effect did not correlate with systolic or diastolic WCE or masked effect (r = -0.05 to 0.08, P > 0.39). In regression analysis, age, baseline mean arterial pressure and BMI were not significantly associated with WCE (all P values >0.4). BP differences between home and office can largely be attributed to the hospital environment rather than to the entrance of the physician. The physician-related BP effect is not related to differences of HBP and OBP.

THE INFLUENCE OF OBESITY ON CIRCADIAN BLOOD PRESSURE PATTERNS: A DIETARY INTERVENTION STUDY

In healthy individuals, blood pressure follows a circadian pattern with typically a 10% or more drop in blood pressure nocturnally. Individuals with a lack of nocturnal dipping or rises in nocturnal blood pressure from daytime have an increased risk of many cardiovascular disease, including strokes, heart failure and renal failure. Limited treatment options exist for individuals with such abnormal nocturnal blood pressure patterns, especially if they do not also have a secondary trigger, such as sleep apnea. In this study, we examine a potential correlation between obesity and nocturnal blood pressure abnormalities, including blood pressure non-dipping, and a rise of blood pressure nocturnally, as well as the impact of weight reduction through dietary intervention, on nocturnal blood pressure. We recruited 30 volunteers with a lack of nocturnal dip pattern, 30 volunteers with blood pressure that rises nocturnally from daytime and 20 control volunteers with a healthy nocturnal dip. Individuals with known sleep apnea were excluded. 24-hour ambulatory blood pressure monitoring and BMI measurements were performed before and after a 2 month dietary and lifestyle intervention wherein patients were counseled on the DASH diet and lifestyle program with a targeted 5% weight loss. There was a negative, linear relationship at baseline between the BMI and the abnormalities of nocturnal blood pressure patterns; the average BMI of the control group with a healthy dip in blood pressure nocturnally was 28.1 kg/m2, the average BMI of the group with a lack of nocturnal “dip” was 30.3 kg/m2 and the average BMI of the rise of nocturnal blood pressure group was 35.3 kg/m2 (p<0.0001, r=0.600). After the 2 month dietary intervention, we observed that individuals with abnormal baseline nocturnal blood pressure who achieved a weight loss of 5% or more had an average 8.4% dip in nocturnal blood pressure after the dietary intervention, representing a significant improvement in circadian blood pressure patterns. Those who did not achieve a 5% weight loss & those who gained weight had blood pressure that continued to show an aberrant circadian blood pressure pattern with an average persistent 3.2% rise in BP nocturnally (p<0.0001). The findings of this study suggest that obesity may be an important contributor to nocturnal BP abnormalities. Weight loss, through diet and lifestyle modifications, may improve nocturnal blood pressure pattern, restoring a healthy circadian blood pressure cycle.

Elevated Serum Level of Interleukin 17 in a Population With Prehypertension.

Cytokines play an important role in the pathogenesis of hypertension. The authors hypothesized that interleukin 17 (IL-17) might contribute to the prehypertensive state. This study evaluated the relationship between serum levels of IL-17 and prehypertension. A total of 394 participants were enrolled, after excluding for hypertension or treated hypertension, and divided into two groups (optimal blood pressure [BP] and prehypertension) based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classification of BP. Optimal BP was defined as systolic BP <120 mm Hg and diastolic BP <80 mm Hg. Prehypertension was defined as systolic BP of 120 to 139 mm Hg or diastolic BP of 80 to 89 mm Hg. IL-17A levels were determined by enzyme-linked immunosorbent assay. The mean serum IL-17 concentration in the prehypertension group was significantly higher than in the optimal BP group. The cohort was divided into quartiles Q1 (≤3.5 ng/L), Q2 (3.60 to 6.10 ng/L), Q3 (6.20 to 10.00 ng/L), and Q4 (≥10.10 ng/L) based on IL-17 levels. The Q2 to Q4 groups had increasing odds ratios for having prehypertension compared with the Q1 group. Elevated serum IL-17 was accompanied by a rise in systolic BP. Thus, increased serum IL-17 levels are associated with prehypertension.

Large artery stiffness and hypertension after antiangiogenic drugs: influence on cancer progression.

Systemic hypertension is a frequent side effect of antiangiogenic drugs (AADs) and may represent a marker of efficacy on cancer. We hypothesized that large artery properties are affected by AADs, and contribute to the rise of blood pressure and may be better related to cancer progression and mortality than hypertension. Participants were studied before AADs (V0), 10 days later (V1) and then every 2 weeks for 6 weeks (V1-V4). We included 57 consecutive patients in whom treatment with sorafenib (400 mg twice daily) or sunitinib (37.5-50 mg once daily) was indicated. The target dose could be adjusted according to tolerance and response. Aortic and carotid stiffness, brachial and central blood pressure and augmentation index were measured noninvasively at each visit. Data regarding cancer progression and mortality were collected at 6 months. Twenty-eight patients (49%) developed hypertension. Brachial SBP significantly increased during follow-up (V0-V1: +9.6 ± 15.2 mmHg, P < 0.001; V0-V4: +6.0 ± 17.8 mmHg, P = 0.04). Central BP, and aortic and carotid stiffness increased independently of brachial BP changes. Aortic and carotid stiffening were associated with cancer progression independently of BP changes [hazard risk 1.24 (1.01-1.51) and 1.34 (1.03-1.73), respectively; P < 0.05], but not with cancer mortality. Brachial SBP had no predictive value. Large arteries stiffen during AAD treatment partly independently of BP changes. Arterial mechanical properties are associated with BP rise. Arterial stiffening is related with the effects of AAD on cancer progression independently of BP changes. Large artery properties might help monitor AAD therapy in cancer patients.

Effect of Salt Diet on Beat‐to‐Beat Blood Pressure Dynamics in Hypertensive and Non‐hypertensive Rats

ObjectivesBlood pressure normally exhibits substantial short and long term variability (BPV). We assessed, in salt sensitive hypertensive (SS) and non‐hypertensive (SSBN13) Dahl rats, the impact of high (HS) versus low (LS) salt diet on beat‐to‐beat BPV indices including correlation properties (detrended fluctuation analysis scale coefficient α) and complexity (Sample Entropy; SpEn)MethodsBP data were analyzed from 9 SS [HTN] and 6 SSBN13 [No‐HTN] rats: 1) after 9 weeks of LS diet (0.4%), and 2) repeated after 2 weeks of HS diet (8%). Beat‐to‐beat systolic and diastolic BP series were derived from 2‐minute data epochs (Physionet.org). SpEn, coefficient α, standard deviation (SD) and coefficient of variation (CV, %) were comparedResultsMean systolic and diastolic BP increased on HS – particularly in SS rats (Table). SD and CV were similar across groups irrespective of diet. On LS, HTN and No‐HTN exhibited similar systolic and diastolic complexity and correlation indices. On HS, 1) HTN showed an increased α (smoother) for systolic (p=0.015) and diastolic (p=0.021) BP; 2) No‐HTN showed lower SpEn (less complex) for systolic and diastolic BP (p=0.046), while corresponding α were unchanged; and 3) HTN showed higher systolic (p=0.003) and diastolic (p=0.001) α compared to No‐HTN. Changes in α (ΔHS‐LS) were greater in HTN versus No‐HTN rats for diastolic (p=0.034) and systolic (p=0.099) BP seriesConclusionHypertensive rats are more susceptible to HS with a greater rise in mean BP and reduced complexity. Yet, the comparable mean pressures in HTN and No‐HTN rats when on LS diet coupled with similar BPV dynamics suggest a protective role of low salt diet in hypertensive ratsFunding: None Study Group SS rats (HTN) SSBN13 rats (No‐HTN) Teatment LS HS ΔHS‐LS LS HS ΔHS‐LS Systolic BP mmHg 137±2ab 195±7ab 57±5b 125±2ab 155±3ab 30±2b α 0.94±0.04a 1.15±0.04ab 0.21±0.05 0.91±0.05 0.97±0.02b 0.07±0.04 SpEn 1.43±0.06 1.26±0.06 0.16±0.10 1.51±0.09a 1.24±0.08a ‐0.28±0.09 SD 4.40±0.30 5.73±0.46 1.33±0.57 4.30±1.30 5.19±0.49 0.89±0.59 CV(%) 3.2±0.2 2.9±0.2 0.26±0.34 3.5±0.4 3.4±0.4 ‐0.07±0.48 Diastolic BP mmHg 102±3a 153±7ab 51±6b 97±1a 123±3ab 26±3b α 0.98±0.04a 1.17±0.04ab 0.18±0.06b 0.94±0.04 0.95±0.01b 0.01±0.04b SpEn 1.27±0.04 1.03±0.09 0.24±0.14 1.37±0.06a 1.21±0.02a ‐0.16±0.06 SD 4.03±0.31 4.70±0.48 0.67±0.59 3.80±0.50 4.65±0.56 0.85±0.58 CV(%) 3.97±0.25 3.13±0.29 0.85±0.41 3.89±0.47 3.82±0.47 ‐0.08±0.48 Nbeats: 626‐953; data shown as mean±std err; a = P&lt;0.05 LS vs HS (within‐group); b = P&lt;0.05 SS vs SSBN13 (between‐groups; same treatment); comparisons using the rank sum and the sign rank test as appropriate

Study of autonomic functions in young adults of hypertensive and normotensive parents

Background: Hypertension is a major public health problem worldwide, including India. Nowadays, prehypertension is common in young adults. It has genetic basis and runs in families. Parental history of hypertension increases the risk of developing hypertension, especially if both parents are hypertensive. Cause & effect relation of hypertension & autonomic dysfunction is not clear. Therefore, this study was planned to see autonomic function alterations in young adults of hypertensive parents, if any.Methodology: In this study autonomic activity was assessed in students with both parents hypertensive (n= 30), one parent hypertensive (n= 30) and both parents normotensive (n= 30).Resting heart rate and BP was measured for parasympathetic function assessment and rise in diastolic BP with hand grip dynamometer was used for sympathetic function assessment.Results: The study showed no significant difference in resting pulse rate of all the groups. BP was slightly higher in groups with hypertensive parents as compared to a group of normotensive parents, but the difference was statistically insignificant. Statistically significant rise in diastolic BP with handgrip dynamometer was observed in subjects with hypertensive parents.Conclusion: This rise in diastolic BP indicates increased sympathetic activity. Our results showed higher sympathetic activity in those with hypertensive parents. It also confirmed the genetic basis of sympathetic (vasomotor) tone. Young adults having hypertensive parents are at a greater risk of hypertension at an early age. Regular assessment of blood pressure and autonomic function with lifestyle modifications should be recommended to delay onset of hypertension in them.

Recent clinical and translational advances in pediatric hypertension.

Epidemiological reports describe a child population increase in BP level and an increase in prevalence of hypertension, that is largely, but not entirely, driven by a concurrent increase in childhood obesity. Given current estimates, ≈10% of adolescents have hypertension or prehypertension. In addition to obesity, dietary salt intake and waist circumference, a marker of visceral obesity, are found to be independently associated with the rise in BP among children and adolescents. Dietary salt intake in urban children is well above recommended levels largely because of consumption of processed and fast foods. Childhood exposures, such as stress,52 salt, and fructose, as well as lifestyles, including food sources, sleep patterns, and reductions in physical activity may have a role in obesity-high BP associations. In addition, clinical and translational evidence is mounting that intrauterine exposures alter can effect changes in fetal development that have an enduring effect on cardiovascular and metabolic function later in life. These effects can be detected even in children who are products of a term otherwise normal pregnancy. Hypertension in childhood has been defined statistically (BP ≥ 95th percentile) because of lack of outcome data that links a BP level with heightened risk for future cardiovascular events. Therefore, primary hypertension had been considered a risk factor for later hypertension in adulthood. Intermediate markers of TOD, including cardiac hypertrophy, vascular stiffness, and increases in cIMT, are detectable in adolescents with primary hypertension. Evidence that vascular injury is present in the early phase of hypertension and even in prehypertension warrants consideration on the current definition of pediatric hypertension. With further studies on TOD and other risk factors in addition to high BP, it may be possible to shift from a statistical definition to a definition of childhood hypertension that is evidence based. Preventing or reducing childhood obesity would have substantial benefit in countering the documented increase in BP levels and prevalence of high BP in childhood. Weight control in overweight and obese children, along with dietary changes 53 and increases in physical activity,54 has benefit on BP levels in childhood. Prevention of childhood obesity and BP risk will require multiple levels of intervention, including public health, health policy, and attention to food supply to foster the necessary lifestyle changes to prevent and reduce childhood obesity.

IMPROVEMENT OF AMLODIPINE CONTROL EFFICACY OVER HYPERTENSION USING FIXED COMBINATION OF PERINDOPRIL ARGININE AND AMLODIPINE

Aim. To evaluate possibilities of hypertension control improvement using fixed combination of perindopril arginine and amlodipine. Material and methods. Totally 46 patients studied (25 men, 21 women of the age 53,6±4,3y.)with arterial hypertension 2-3 grade. All patients underwent ABPM with analysis of the following: mean 24-hour BP, velocity of morning SBP and DBP rise, BP variability of Ps BP (VPsBPd, VPsBPn). The criteria of inclusion were insufficient control over hypertension while using free combinations of ACE inhibitor or angiotensin II receptor blockers and diuretic or calcium channel blocker. To control arterial hypertension all patients were prescribed the fixed combination of perindopril arginine/amlodipine it standard dosage 10/5 mg (Prestans, Les Laboratories Servier, France) with further possible increase of dosage up to 10/10 mg. Results. While receiving the therapy 84,7% patients reached BP. Mean 24-hour SBP decreased from 139,24±1,8to 121,13+1,22 mmHg (p<0,05), DBP decreased from 84,51±2,08 to 73,14±1,4 (p<0,05), mean BP decreased from 103,07±1,56 to 87,66±1,13 (p<0,05). 24-hour variability of SBP significantly decreased from 15,28±0,72 to 10,21±0,42 (p<0,05), DBP from 13,46±0,72 to 10,72±0,31 (p<0,001). Values of VMR after the treatment also decreased. Before treatment VMR of SBP was 27±3,26 mmHg/hour, on therapy — 15,3±5,04 mmHg/hour, (p<0,01); the same for DBP — VMR decreased from 23,6±2,37 mmHg/hour to 11±1,62mmHg, (p<0,01). Conclusion. The usage of combined perindopril arginine/amlodipine in patients with former uncontrolled arterial hypertension at the background of free chosen antihypertensive drugs combinations succeeded in the target BP values achievement in 84,7% cases. The reached control over BP was successful daily and during the night, as over variability of BP and velocity of morning BP rise. Usage of fixed combination of perindopril arginine/amlodipine was marked with good tolerability and high patients' compliance.

Blood Pressure Profile and Hypertension in Urban Adolescents: Need for Cognisance

Objective: To find the profile of blood pressure and the prevalence of hypertension in adolescents in an urban area. Methods: A cross sectional study was carried out in Adolescent students in the age group of 11-17 years, in a school in an urban area of Pune, belonging to upper socioeconomic group to measure their blood pressure and anthropometric parameters.Results: The mean SBP and DBP in both boys and girls were found to increase with increasing age and anthropometric measurements. The prevalence of hypertension was 12.23% in boys and 10.1% in girls and the prevalence of overweight as per BMI was 19.14% in boys and 18.62% in girls. The prevalence of hypertension observed in overweight children (36.1% in boys 30.8% in girls) was significantly (p&lt;0.000) higher than normal weight children (6.5% in boys and 5.36% in girls). Among the anthropometric variables only weight &amp; BMI had moderately strong correlation with SBP(r-0.559 &amp;0.506).Conclusion: Hypertension is prevalent among adolescent population and overweight/obesity has been found to play a crucial role in predicting rise in BP in them. It is recommended bp monitoring be made mandatory part of school health services programme for early detection &amp; instituting preventive measures.DOI: http://dx.doi.org/10.3126/jnps.v34i2.10743J Nepal Paediatr Soc 2014;34(2):85-89

Abstract 098: Foxp3+ T Regulatory Lymphocytes Counteract Angiotensin Ii-induced Vascular Injury

Objective: T effector lymphocytes contribute to vascular injury in angiotensin (Ang) II-induced hypertension, but the role of T regulatory lymphocytes (Tregs) is unclear. Ang II-induced hypertension is blunted in T and B lymphocyte-deficient (Rag1-/-) mice, and restored with reconstitution of T cells. We hypothesized that adoptive transfer of FOXP3-deficient Scurfy (Sf) vs. wild-type (WT) T cells will exacerbate Ang II-induced vascular damage in Rag1-/- mice. Methods: Eleven-week old male Rag1-/- mice were injected IV with vehicle, 10 million WT or Sf T cells, 1 million CD4+CD25+ Tregs alone or with Sf T cells, and 2 weeks later were infused or not with Ang II (490 ng/kg/min, SC) for 14 days (n=3-8). Telemetric BP, vascular function and structure, and reactive oxygen species (ROS) production and fibronectin expression in mesenteric arteries (MA) were determined. Results: Ang II induced a 40 mmHg systolic BP rise in all the groups, but diastolic BP rise was ~10 mmHg greater in WT and Sf T cell-injected mice than in controls (P&lt;0.01). Treg injection alone or with Sf T cells prevented or delayed by 7 days the BP rise, respectively (P&lt;0.05). Ang II did not induce endothelial dysfunction in vehicle or Treg only-injected mice. Adoptive transfer of WT T cells restored Ang II induced-endothelial dysfunction (60±5% vs. 83±4%, P&lt;0.05), which was exaggerated in Sf T cell-injected mice (56±6% vs. 97±7%, P&lt;0.01), but reduced by Treg co-injection (74±4%, P&lt;0.05). Ang II increased ROS production in MA wall (239±32% vs. 119±20%) and perivascular fat (369±39% vs. 84±8%) in Sf T cell-injected mice (P&lt;0.01), but not when co-injected with Tregs. Ang II induced increased vascular stiffness (P&lt;0.01) and media/lumen (M/L, P&lt;0.05) in vehicle (strain at 140 mmHg: 0.60±0.02 vs. 0.80±0.02; M/L: 4.1±0.2 vs. 2.9±0.2%) and Sf T cell-injected mice (strain at 140 mmHg: 0.63±0.01 vs. 0.89±0.04; M/L: 4.7±0.3 vs. 2.9±0.1%). Ang II increased MA fibronectin expression (P&lt;0.01) in vehicle (113±12 vs. 51±14 RFU/μm2) and Sf T cell-injected mice (85±7 vs. 36±9 RFU/μm2). Conclusion: These results demonstrate that Foxp3+ Tregs have a protective role against Ang II-induced vascular dysfunction, remodeling and oxidative stress.

Abstract 528: Dose- And Salt-dependency Of Angiogenesis Inhibition-induced Blood Pressure Rise And Renal Toxicity

Angiogenesis inhibition with the VEGF inhibitor sunitinib is an established anti-cancer therapy, inducing hypertension and nephrotoxicity. We explored the dose- and salt-dependency of these side effects. In male WKY rats, mean arterial pressure (MAP) was monitored telemetrically during oral treatment with a high (27.5 mg/kg.day, n=14), an intermediate (14 mg/kg.day, n=6) and low dose (7 mg/kg.day, n=6) of sunitinib or vehicle (n=8) after normal salt diet for 2 weeks. The low dose-model was also combined with a high salt diet (8% NaCl and saline water). Eight days after administration rats were sacrificed and blood and 24h urine samples collected for biochemical measurements. With the high dose of sunitinib, MAP increased from 94.7±0.9 mmHg to 125.8±1.5 mmHg (Δ31.1±0.9 mmHg, p&lt;0.001). The intermediate and low doses induced MAP rises of 24.3±2.7 mmHg (p&lt;0.001) and 13.4±3.3 mmHg (p&lt;0.001), respectively. The low dose of sunitinib with high salt, induced a MAP rise of 43.5±2.2 mmHg (p&lt;0.001 compared to normal salt). With the high dose, circulating ET-1 increased from 0.6±0.1 pg/ml to 1.6±0.2 pg/ml (p&lt;0.01) and serum cystatine-C from 4.5±0.1 mg/L to 6.6±0.3 mg/L (p&lt;0.001). Comparable increases in circulating ET-1 were seen with the intermediate and low doses, whereas serum cystatine-C did increase with the intermediate dose (to 6.3±0.1 mg/L, p0.05). Serum cystatine-C levels with low and high salt were identical. With the high dose of sunitinib, proteinuria increased from 7.5±1.3 to 33.3±4.8 mg/day (p&lt;0.05). The rise in proteinuria was attenuated with the intermediate (16.2±2.1 mg/day, p&lt;0.01) and low dose (19.9±3.3 mg/day, p&lt;0.01), but increased to 40.4±30.1 mg/day (p&gt;0.05) with high salt. Angiogenesis inhibition-induced hypertension and nephrotoxicity are dose-dependent with a lower threshold for the rise in BP than for renal toxicity. The BP rise observed with the low dose of sunitinib observed in normotensive rats is comparable to the sunitinib-induced BP rise observed in patients and clearly is salt-sensitive. Since cystatine-C levels during normal and high salt diet were comparable, the BP rise during high salt seems independent of renal dysfunction.

GABA Derivatives Citrocard and Salifen Reduce the Intensity of Experimental Gestosis

Substitution of drinking water with 1.8 % NaCl solution in pregnant female rats from day 1 of gestation until parturitions was followed by the development of experimental gestosis. Gestosis manifested in an increase in BP by 18.2 %, protein concentration in the urine by 6.2 times, and edema severity in muscles, brain, and omentum in comparison with the initial level. The concentration of homocysteine in blood plasma of rats with complicated pregnancy 4.4-fold surpassed that in pregnant rats without gestosis, which can probably in a cause for gestosis development. GABA derivatives citrocard (50 mg/kg) and salifen (15 mg/kg), and the reference substance sulodexide (30 U/kg) reduced the severity of gestosis manifestations, which was seen from the absence of BP rise, decrease in urinary protein concentration by 1.9, 2.0, and 1.3 times and blood level of homocysteine by 1.7, 1.5, and 2.6 times, respectively, and a decrease in edema degree in comparison with female rats with experimental gestosis receiving physiological saline.

Predictors of Mean Arterial Pressure Morning Rate of Rise and Power Function in Subjects Undergoing Ambulatory Blood Pressure Recording

BackgroundWe determined clinical predictors of the rate of rise (RoR) in blood pressure in the morning as well as a novel measure of the power of the BP surge (BPpower) derived from ambulatory blood pressure recordings.MethodsBPpower and RoR were calculated from 409 ambulatory blood pressure (ABP) recordings from subjects attending a cardiovascular risk clinic. Anthropometric data, blood biochemistry, and history were recorded. The 409 subjects were 20–82 years old (average 57, SD = 13), 46% male, 9% with hypertension but not on medication and 34% on antihypertensive medication.ResultsAverage RoR was 11.1 mmHg/hour (SD = 8) and BPpower was 273 mmHg2/hour (SD = 235). Only cholesterol, low density lipoprotein and body mass index (BMI) were associated with higher BPpower and RoR (P<0.05) from 25 variables assessed. BPpower was lower in those taking beta-blockers or diuretics. Multivariate analysis identified that only BMI was associated with RoR (4.2% increase/unit BMI, P = 0.020) while cholesterol was the only remaining associated variable with BPpower (17.5% increase/mmol/L cholesterol, P = 0.047). A follow up of 213 subjects with repeated ABP after an average 1.8 years identified that baseline cholesterol was the only predictor for an increasing RoR and BPpower (P<0.05). 37 patients who commenced statin subsequently had lower BPpower whereas 90 age and weight matched controls had similar BPpower on follow-up.ConclusionsCholesterol is an independent predictor of a greater and more rapid rise in morning BP as well as of further increases over several years. Reduction of cholesterol with statin therapy is very effective in reducing the morning blood pressure surge.

Nicotine Exposure, Blood Pressure, and Inflammation in Tobacco Smokers and Chewers in a Rural Community in Nepal

Tobacco consumption is high amongst the people of Nepal. This study was carried out in 2011 in a rural community of Nepal, to compare pathological parameters associated with tobacco use in relation to nicotine metabolism between smokers, chewers, and a control group. A total of 216 volunteers provided blood and urine samples for testing nicotine metabolites, C-reactive protein, and cell counts. Data were analyzed using ANOVA, correlation, and t-tests using STATA. Differences in blood pressure amongst the groups indicate a role of smoking in preventing a rise in BP with age, likely attributable to a different mechanism of metabolism of tobacco constituents.

THE STUDY OF AUTONOMIC FUNCTION TESTS IN PATIENTS OF RHEUMATOID ARTHRITIS BY CARDIOVASCULAR ANALYSIS SYSTEM

involvement has rarely been studied and has shown conflicting results. This study was conducted to investigate ANS dysfunction in patients of RA by CANWin using classical Ewing autonomic battery tests. Methods: 50 patients of RA between the age group of 20-70 years along with 25 healthy age and sex matched controls were evaluated by 4 parasympathetic tests including resting heart rate (HR), HR response to deep breathing, standing and valsalva maneuver; and 2 sympathetic tests consisting of blood pressure response to standing and sustained hand grip (SHG) by CANWin analysis system (Window based). Results: Heart rate response to deep breathing (E:I), standing (30:15 ratio) and valsalva showed very significant results in patients of RA as compared to that of controls (P<0.01). 10% of RA patients showed fall in systolic BP on standing by more than 20 mm Hg as compared to controls (0%) with significant p-value of <0.05. 20% of RA patients showed abnormal low rise in diastolic BP on SHG with significant p-value of <0.05. Interpretation & Conclusions: This study has confirmed the presence of cardiac autonomic nervous system dysfunctions including both

Early to mid‐Holocene rapid sea‐level rise and coastal response on the southern Yangtze delta plain, China

ABSTRACTWe used accelerator mass spectrometry (AMS) 14C‐dated sediments of the Holocene basal supratidal flat to upper tidal flat facies in 11 cores on the southern Yangtze delta plain to reconstruct relative sea levels of 8.5–8.0 cal ka BP. Three cores were further AMS 14C dated and used to examine the evolution of sedimentary geomorphological environments in response to the rapid sea‐level rise during the early to mid‐Holocene. Results demonstrate relative sea‐level rise of around 30 mm a−1 from 8.5 to 8.3 cal ka BP and around 10 mm a−1 from 8.3 to 8.0 cal ka BP. Retrogradation from supratidal to lower tidal flat environments occurred in response to the rapid sea‐level rise at 8.5–8.3 cal ka BP, and aggradation from middle to upper tidal flat occurred at 8.3–7.9 cal ka BP. Further retreat of the tidal flat at 7.9–7.2 cal ka BP implies a mean sea‐level rise rate exceeding 5 mm a−1 at this time. We suggest that the rapid relative sea‐level rise during 8.3–8.5 cal ka BP and subsequent slower rise caused drastic changes in the coastal zone and that these changes are key phenomena for understanding the coastal response to future sea‐level rise.

Dietary Sodium Restriction and Association with Urinary Marinobufagenin, Blood Pressure, and Aortic Stiffness

Systolic BP and large elastic artery stiffness both increase with age and are reduced by dietary sodium restriction. Production of the natriuretic hormone marinobufagenin, an endogenous α1 Na+,K+-ATPase inhibitor, is increased in salt-sensitive hypertension and contributes to the rise in systolic BP during sodium loading. The hypothesis was that dietary sodium restriction performed in middle-aged/older adults (eight men and three women; 60 ± 2 years) with moderately elevated systolic BP (139 ± 2/83 ± 2 mmHg) would reduce urinary marinobufagenin excretion as well as systolic BP and aortic pulse-wave velocity (randomized, placebo-controlled, and crossover design). This study also explored the associations among marinobufagenin excretion with systolic BP and aortic pulse-wave velocity across conditions of 5 weeks of a low-sodium (77 ± 9 mmol/d) and 5 weeks of a normal-sodium (144 ± 7 mmol/d) diet. Urinary marinobufagenin excretion (weekly measurements; 25.4 ± 1.8 versus 30.7 ± 2.1 pmol/kg per day), systolic BP (127 ± 3 versus 138 ± 5 mmHg), and aortic pulse-wave velocity (700 ± 40 versus 843 ± 36 cm/s) were lower during the low- versus normal-sodium condition (all P<0.05). Across all weeks, marinobufagenin excretion was related with systolic BP (slope=0.61, P<0.001) and sodium excretion (slope=0.46, P<0.001). These associations persisted during the normal- but not the low-sodium condition (both P<0.005). Marinobufagenin excretion also was associated with aortic pulse-wave velocity (slope=0.70, P=0.02) and endothelial cell expression of NAD(P)H oxidase-p47phox (slope=0.64, P=0.006). These results show, for the first time in humans, that dietary sodium restriction reduces urinary marinobufagenin excretion and that urinary marinobufagenin excretion is positively associated with systolic BP, aortic stiffness (aortic pulse-wave velocity), and endothelial cell expression of the oxidant enzyme NAD(P)H oxidase. Importantly, marinobufagenin excretion is positively related to systolic BP over ranges of sodium intake typical of an American diet, extending previous observations in rodents and humans fed experimentally high-sodium diets.