Blood Pressure Rhythm Research Articles

Therapeutic effect of adjuvant treatment of acupuncture in a period of day from 7:00 am to 9:00 am on non-dipper essential hypertension

To compare the infuences on circadian rhythm of blood pressure in the patients with non-dipper essential hypertension between the combined treatment of time acupuncture and western medication and the simple western medication. A total of 70 patients with non-dipper essential hypertension were randomized into an acupuncture plus western medication group (35 cases, 2 cases dropped out) and a western medication group (35 cases). In the western medication group, levamlodipine maleate tablets were taken orally, 2.5 mg each time, once daily. In the acupuncture plus western medication group, on the base of the treatment as the western medication group, acupuncture was applied specially in the period of the day from 7:00 am to 9:00 am. The acupoints included Fengchi (GB 20), Zhongwan (CV 12), Tianshu (ST 25), Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36), etc. Acupuncture was given once daily, 5 treatments a week. The duration of treatment in the two groups was 4 weeks. The clinic blood pressure before and after treatment, 24 h ambulatory blood pressure and the levels of serum melatonin (MT) and 5-serotonin (5-HT) were observed in the two groups. The total effective rate of anti-hypertension was 75.8% (25/33) in the acupuncture plus western medication group, better than 54.3% (19/35) in the western medication group (P<0.05). The 24 h average systolic blood pressure, the daytime average systolic blood pressure, the daytime average diastolic pressure, and the nighttime average systolic blood pressure were all reduced after treatment in the two groups (P<0.05). The reduction effect of the aforementioned 4 indexes in the acupuncture plus western medication group was much more obvious as compared with the western medication group (P<0.05). After treatment, the serum level of MT was increased and 5-HT decreased in the patients of two groups (P<0.05). The serum level of MT in the acupuncture plus western medication group was higher than that in the western medication group and the level of 5-HT was lower than the western medication group (P<0.05). Time acupuncture therapy in the period of the day from 7:00 am to 9:00 am, combined with western medication effectively reduce blood pressure and regulate the levels of serum MT and 5-HT so as to maintain the circadian rhythm of blood pressure in patients with non-dipper essential hypertension. The therapeutic effect of this combined treatment is superior to simple western medication.

Clinical Implications

Clinical Implications

0349 Circadian Patterns of Blood Pressure Differ Between Retired Night Shift Workers and Retired Day Workers

Abstract Introduction Approximately 15% of full-time employees in the U.S. work outside the traditional daytime schedule. These individuals exhibit circadian rhythm abnormalities and increased rates of cardiovascular disease compared to day shift workers. Altered circadian patterns of cardiovascular function may persist into retirement even after returning to a normal nocturnal sleep schedule, and may contribute to the elevated cardiovascular disease burden among retired night shift workers. The purpose of this study was to determine whether circadian rhythms of cardiovascular indicators differed between retired night shift workers and retired day workers. Methods Participants (N = 72, 53% females, 83% non-Hispanic White, mean age: 68.66 years) were 33 retired night shift workers and 39 retired day workers who completed a 60-hour sleep/circadian laboratory assessment. Blood pressure and heart rate were assessed hourly during a 24-hour constant routine protocol. Multilevel cosinor analysis estimated group differences in circadian rhythms of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR). Covariates included age, sex, race, education, and body mass index. Results The 24-hour pattern of DBP (bsine*shiftwork = 1.47, [95% CI: 0.58, 2.35], p = 0.002) and MAP (bsine*shiftwork = 1.38, [95% CI: 0.28, 2.50], p = 0.015) differed between retired night shift workers and retired day workers. Retired night shift workers displayed a later trough of DBP and MAP compared to retired day workers. No group differences were found for circadian rhythms of SBP or HR. Conclusion Retired night shift workers exhibited altered circadian rhythms of blood pressure, which may indicate a circadian “scarring” of night shift work that persists after a return to normal daytime schedule. Future research should investigate explanations for observed differences and the extent to which chronic alterations in cardiovascular circadian rhythms affect morbidity and mortality. Support R01AG047139, T32HL082610, T32HL07560, UL1TR001857

Diurnal Timing Dependent Alterations in Gut Microbial Composition Are Synchronously Linked to Salt-Sensitive Hypertension and Renal Damage.

Alterations of diurnal rhythms of blood pressure (BP) and reshaping of gut microbiota are both independently associated with hypertension. However, the relationships between biorhythms of BP and gut microbial composition are unknown. We hypothesized that diurnal timing-associated alterations of microbial compositions are synchronous with diurnal rhythmicity, dip in BP, and renal function. To test this hypothesis, Dahl salt-sensitive (S) rats on low- and high-salt diets were examined for time of day effects on gut microbiota, BP, and indicators of renal damage. Major shifts in night and day patterns of specific groups of microbiota were observed between the dark (active) and light (rest) phases, which correlated with diurnal rhythmicity of BP. The diurnal abundance of Firmicutes, Bacteroidetes, and Actinobacteria were independently associated with BP. Discrete bacterial taxa were observed to correlate independently or interactively with one or more of the following 3 factors: (1) BP rhythm, (2) dietary salt, and (3) dip in BP. Phylogenetic Investigation of Communities revealed diurnal timing effects on microbial pathways, characterized by upregulated biosynthetic processes during the active phase of host, and upregulated degradation pathways of metabolites in the resting phase. Additional metagenomics functional pathways with rhythm variations were noted for aromatic amino acid metabolism and taurine metabolism. These diurnal timing dependent changes in microbiota, their functional pathways, and BP dip were associated with concerted effects of the levels of renal lipocalin 2 and kidney injury molecule-1 expression. These data provide evidence for a firm and concerted diurnal timing effects of BP, renal damage, and select microbial communities.

Circadian Regulation of Blood Pressure: of Mice and Men.

Blood pressure (BP) exhibits strong diurnal variations that have been shown to be important for normal physiology and health. In this review, we highlight recent advances in both basic and clinic research on how the circadian clock affects these BP rhythms. Tissue-specific and inducible knockout rodent models have provided novel ways to dissect how circadian clocks regulate BP rhythms and demonstrated that loss of these rhythms is associated with the development of disease. The use of circadian-specific research protocols has translated findings from rodent models to humans, providing insight into circadian control of BP, as well as how sleep, activity, and other factors influence diurnal BP rhythms. Circadian mechanisms play an important role in the regulation of diurnal BP rhythms. Future research needs to extend these findings to clinical populations and determine the extent to which circadian factors may play a role in the development of novel treatment approaches to the management of hypertension.

Diurnal Control of Blood Pressure Is Uncoupled From Sodium Excretion.

The diurnal rhythms of sodium handling and blood pressure are thought to be regulated by clock genes, such as Bmal1. However, little is known about the regulation of these factors by Bmal1, especially in rats. Using a novel whole-body Bmal1 knockout rat model (Bmal1-/-), we hypothesized that time of day regulation of sodium excretion is dependent on Bmal1. Using telemetry to continuously record mean arterial pressure, we observed that male and female Bmal1-/- rats had significantly reduced mean arterial pressure over the course of 24 hours compared with littermate controls. The circadian mean arterial pressure pattern remained intact in both sexes of Bmal1-/- rats, which is in contrast to the Bmal1-/- mouse model. Male Bmal1-/- rats had no significant difference in baseline sodium excretion between 12-hour active and inactive periods, indicating a lack of diurnal control independent of maintained mean arterial pressure rhythms. Female Bmal1-/- rats, however, had significantly greater sodium excretion during the active versus inactive period similar to controls. Thus, we observed a clear dissociation between circadian blood pressure and control of sodium excretion that is sex dependent. These findings are consistent with a more robust ability of females to maintain control of sodium excretion, and furthermore, demonstrate a novel role for Bmal1 in control of diurnal blood pressure independent of sodium excretion.

Prognostic Value of a Riser Pattern of Nighttime Blood Pressure in Very Elderly Adults of ≥80 Years: A General Practice-Based Prospective SEARCH Study.

We examined our hypothesis that participants with higher mean nighttime blood pressure (BP) levels and/or those with a riser BP pattern, both measured by ambulatory blood pressure (BP) monitoring (ABPM), would show higher risk for cardiovascular disease (CVD) events compared to those with normal nighttime BP levels or a normal dipper BP pattern of circadian BP rhythm, even in very elderly participants in a general practice population. This prospective observational study enrolled 485 very elderly outpatients of ≥80 years (mean age: 83.2 ± 3.3 years; 44.7% male; 89.3% using antihypertensive medications). The prevalences of extreme dipper, dipper, nondipper, and riser status were 15.5%, 38.6%, 32.2%, and 13.8%, respectively. During a mean follow-up of 3.9 years (1,734 person-years), 41 CVD events occurred. The participants with a riser pattern (higher nighttime systolic BP [SBP] than daytime SBP) showed a significantly higher risk for CVD events with adjustment for covariates: hazard ratio (HR), 2.61; 95% confidence interval (CI), 1.03-6.62. Even after adjusting for covariates and mean nighttime SBP level, the CVD risks in participants with a riser pattern remained significant: HR, 3.11; 95% CI, 1.10-8.88. On the other hand, all BP variables showed no significant risks for CVD events. In addition, when we divided study participants into quartiles by their ambulatory BP levels, none of the ambulatory BP variables showed a J- or U-shaped relationship with CVD event risk. In very elderly general practice outpatients, a riser BP pattern was significantly associated with CVD events independently of mean nighttime BP.

Food Availability Regulates Circadian Blood Pressure Rhythms in Rats

Blood pressure (BP) changes throughout the day and follows a circadian rhythm that is believed to be controlled by so‐called clock genes. Loss of BP reductions during the sleep period are associated with increased risk of cardiovascular and renal disease. Recent human studies suggest that timing of food intake can affect BP. Therefore, the aim of our study was to determine if food availability affects blood pressure rhythms in the absence of light cues in rats with functional and dysfunctional molecular clocks. Individually housed Bmal1KO rats (n=4) and littermate controls (n=6) were implanted with DSI HD‐S10 telemetry transmitters at 10 weeks of age. Data were collected for 2 minutes every 10 minutes at 1000 samples/second. Animals were given ad lib access to food and water in a 12:12 light/dark (LD) cycle for 2 weeks to establish normal BP rhythms. After 2 weeks, animals were placed in constant darkness (DD) with ad lib food and water for 4 weeks. Food availability was then restricted to 12 hours per day (CT 14.5 to CT 2.5, CT=clock time) under DD conditions (DD‐TRF, TRF=time restricted feeding) for 1 week. Cosinor analysis was performed to determine period, amplitude and phase of activity and systolic blood pressure (SBP) rhythms. In LD conditions, period, amplitude, and phase of SBP and activity were similar between Bmal1KO and control rats. After 4 weeks of DD, control rats had SBP rhythms that peaked at CT 19.9±0.3 hours while Bmal1KO rats had SBP rhythms that peaked at CT 12.0±1.8 hours (p&lt;0.05) indicating a significant change in acrophase. SBP amplitude and period were similar in both groups under DD conditions. For locomotor activity, period was shortened in Bmal1KO rats in DD compared to control rats (control: 24.1±0.01 hours vs. Bmal1‐KO: 23.8±0.08 hours). In DD‐TRF, control rats have SBP rhythms that peak at CT 20.69± 0.44 hours, when food was available. However, SBP rhythms of Bmal1 rats peaked at CT 13.94±3.4 hours. SBP amplitude, period, and activity period were similar between groups during DD‐TRF. These results suggest that food availability and the molecular clock contribute to the timing of systolic blood pressure rhythms in rats.

Sex‐Dependent Interplay of the Circadian Clock Protein PER1 and Aldosterone on Renal Sodium Handling

IntroductionThe molecular circadian clock regulates thousands of genes in a tissue‐specific manner, contributing to 24‐hr circadian rhythms of physiological functions, including blood pressure (BP). Healthy individuals exhibit at least a 10% dip in their BP during rest. Loss of this dip is termed non‐dipping and is associated with higher incidence of adverse cardiovascular outcomes and kidney disease. We have shown that global KO of the circadian clock protein PER1 causes non‐dipping hypertension (HTN) in male, but not female mice, in a model of salt‐sensitive HTN (high salt diet plus DOCP, HSDOCP). The altered rhythms in BP are associated with reduced night/day sodium (Na) excretion, suggesting alterations in rhythms of renal function.HypothesisSince the female global PER1 KO mice do not develop non‐dipping HTN, we hypothesize that the female KO mice will maintain normal rhythms of Na excretion, unlike the male KO mice. Additionally, we hypothesize that sex differences in Na excretion will be associated with differences in the renin‐angiotensin‐aldosterone system (RAAS).MethodsMice were acclimated to metabolic cages followed by 12‐hr urine collections during 3 days each of normal Na diet (NS), high Na (HS) diet, and HSDOCP treatment. Urine Na content was measured by flame photometry. Aldosterone (Aldo) was measured by ELISA. Gene expression studies were performed using quantitative RT‐PCR. Genotype and treatment effects were measured by T‐test and 2‐way ANOVA with or without repeated measures. All studies had 6 mice per group.ResultsUnlike male global PER1 KO mice, female global PER1 KO mice maintain normal Na excretion rhythms on HSDOCP (P&gt;0.05). At baseline, urinary Aldo is significantly increased in the male global PER1 KO mice compared to WT (8.5 vs. 4.2ng/24hr, P&lt;0.05), but not in the female KO (10.1 vs. 8.6 ng/24hr, P&gt;0.05). In response to HSDOCP, WT mice decrease renin expression by 50% (P&lt;0.01), but male global PER1 KO mice fail to decrease renin (P&gt;0.05). Female WT and global PER1 KO respond to HSDOCP by downregulating renin expression by 70% (P&lt;0.001). Kidney‐specific KO of PER1 (KS‐PER1) was generated using KSP‐Cadherin Cre to study the role of PER1 in the Aldo‐sensitive distal nephron and collecting duct. Male KS‐PER1 KO mice have higher cumulative Na balance compared to control mice (3.7mEq vs. 2.7mEq, P&lt;0.01), but maintain night/day Na excretion rhythms. Interestingly, KS‐PER1 KO male mice also have higher plasma Aldo compared to control mice at baseline and after HSDOCP treatment (NS: 21 vs. 12; HSDOCP: 4 vs. 2 pg/mL/gBW, P&lt;0.01).ConclusionsGlobal and KS‐PER1 KO results in altered renal Na handling and changes in Aldo levels in male mice. These differences are not observed in the global female KO mice. These results indicate that PER1 in the distal nephron and collecting duct is important for maintaining electrolyte homeostasis and may affect renal Na handling through a sex‐specific mechanism dependent on the RAAS.Support or Funding InformationNIH/NIDDK R01DK109570 to MLG &amp; AHA Fellowship 18POST34030210 to LGD

Diurnal rhythm of blood pressure in patients with polycythemia vera.

Polycythemia vera increases the risk of hypertension, but there is limited information about the effect on daily blood pressure fluctuations. This study aimed to demonstrate how diurnal blood pressure rhythm is affected in polycythemia vera patients. Fifty (50) patients (33 men; mean age 48 ± 15 years) with a diagnosis of polycythemia vera and 51 age and sex-matched healthy subjects for the control group were prospectively evaluated. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were evaluated by ambulatory blood pressure monitoring (ABPM) as average 24-hour, daytime and nighttime measures. Average 24-hour SBP and DBP, daytime SBP and DBP were similar in both groups. However, nighttime SBP and DBP were significantly higher in the polycythemia vera group compared with the control group (125.3 ± 17.2 and 73.7 ± 12.2 vs. 118.9 ± 12.2 and 69.5 ± 8.5; P = 0.034 and P = 0.044). Both nocturnal SBP fall and nocturnal DBP fall were blunted in the polycythemia vera group compared with the control group (-6.9 ± 8.9 and -11.3 ± 12.2 vs. -11.6 ± 7.7 and -16.3 ± 12.0, respectively). Both hemoglobin and hematocrit levels were positively correlated with nocturnal SBP fall (r = 0.306, P = 0.002 and r = 0.355, P < 0.001; respectively) in all patients. We found that the polycythemia vera group had significantly decreased nocturnal dipping compared with healthy controls. The SBP fall was also positively correlated with hemoglobin and hematocrit levels.

Association of a Disrupted Dipping Pattern of Blood Pressure with Progression of Renal Injury during the Development of Salt-Dependent Hypertension in Rats.

The aim of the present study is to investigate whether a disruption of the dipping pattern of blood pressure (BP) is associated with the progression of renal injury in Dahl salt-sensitive (DSS) hypertensive rats. Seven-week-old DSS rats were fed a high salt diet (HSD; 8% NaCl) for 10 weeks, followed by a transition to a normal salt diet (NSD; 0.3% NaCl) for 4 weeks. At baseline, NSD-fed DSS rats showed a dipper-type circadian rhythm of BP. By contrast, HSD for 5 days caused a significant increase in the difference between the active and inactive periods of BP with an extreme dipper type of BP, while proteinuria and renal tissue injury were not observed. Interestingly, HSD feeding for 10 weeks developed hypertension with a non-dipper pattern of BP, which was associated with obvious proteinuria and renal tissue injury. Four weeks after switching to an NSD, BP and proteinuria were significantly decreased, and the BP circadian rhythm returned to the normal dipper pattern. These data suggest that the non-dipper pattern of BP is associated with the progression of renal injury during the development of salt-dependent hypertension.

CIRCADIAN PROFILE OF VASCULAR TONE AS A BASE FOR THE CIRCADIAN RHYTHM OF BLOOD PRESSURE IN CHILDREN

The review is about modern conceptions of vascular tone regulation and its influence on circadian blood pressure rhythm.

Effects of an SGLT2 inhibitor on the salt sensitivity of blood pressure and sympathetic nerve activity in a nondiabetic rat model of chronic kidney disease.

The glucose-lowering effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors is reduced in patients with diabetes who have chronic kidney disease (CKD). In the present study, we examined the effect of an SGLT2 inhibitor on the salt sensitivity of blood pressure (BP), circadian rhythm of BP, and sympathetic nerve activity (SNA) in nondiabetic CKD rats. Uninephrectomized Wistar rats were treated with adenine (200 mg/kg/day) for 14 days. After stabilization with a normal-salt diet (NSD, 0.3% NaCl), a high-salt diet (HSD, 8% NaCl) was administered. Mean arterial pressure (MAP) was continuously monitored using a telemetry system. We also analyzed the low frequency (LF) of systolic arterial pressure (SAP), which reflects SNA. In adenine-induced CKD rats, HSD consumption for 5 days significantly increased the mean MAP from 106 ± 2 to 148 ± 3 mmHg. However, MAP was decreased to 96 ± 3 mmHg within 24 h after switching back to a NSD (n = 7). Treatment with an SGLT2 inhibitor, luseogliflozin (10 mg/kg/day, p.o., n = 7), significantly attenuated the HSD-induced elevation of MAP, which was associated with a reduction in LF of SAP. These data suggest that treatment with an SGLT2 inhibitor attenuates the salt sensitivity of BP, which is associated with SNA inhibition in nondiabetic CKD rats.

The role of natural light rhythm in the development of desynchronosis in the conditions of rotational shiftwork in the Arctic

Purpose. To study the effects of a natural light cycle on circadian rhythms of blood pressure (BP) and heart rate conditions of rotational shiftwork in the Far North. Material and Methods . Data of 24-h BP monitoring were analyzed in 373 male patients with hypertension stage II monthly round-trip sojourns to the Arctic compared with a similar group of 144 patients living in moderate climate (Tyumen, 57 N). The standard and chronobiological parameters of 24-h BP monitoring were analyzed in 93 randomly selected patients of the Far North group and 64 patients of the Tyumen group. The 24-h BP profile, circadian indices of systolic and diastolic BP, percentage contribution value, rhythm amplitude, acrophase, and diurnal mean value of 24-h BP rhythm were studied during the seasons of the year. Results. The circadian rhythms of HR and BP in hypertensive patients in the conditions of rotational shiftwork in the Arctic showed the signs of internal desynchronosis and significantly differed from those in Tyumen patients independently of a season. The lack of natural light in the Far North during the polar day and polar night resulted in the flattened curves of circadian BP and HR rhythms in the hypertensive patients. Other major differences consisted in the low-amplitude profile of the spectrum and the loss of 24-h component in this group. The seasonal changes in HR in the comparison group were insignificant unlike those in the Far North group, which showed maximum flattening of HR rhythm during the polar day and polar night. Winter season (polar night) was the most adverse for the main group of patients in regard to their 24-h BP profile, which was characterized by the maximum degree of circadian rhythm flattening and the predominance of high-frequency oscillations in the spectrum. Conclusions. The development of circadian and seasonal desynchronosis of the HR and BP rhythms in hypertensive patients in the conditions of rotational shiftwork in the Arctic was caused not only by the labour characteristics and the climatic factors, but also by the natural light rhythmicity in the high latitude.

Diurnal rhythm of blood pressure among Nigerians with hypertension using 24-hour ambulatory blood pressure monitoring.

Introductionhypertension is the most common cardiac disease in Nigeria. There are very limited studies in Nigeria on the use of 24-hour ambulatory blood pressure monitoring (24-h ABPM) for evaluation of hypertensive patients. Twenty four-hour ABPM, unlike office blood pressure (OBP), can assess diurnal variation using parameters like awake blood pressure (BP), asleep (nocturnal) BP, mean 24-hour BP and dipping pattern. This can help in assessment of increased cardiovascular risk and management of hypertensive patients. We purposed to assess the diurnal rhythm of BP among Nigerians with hypertension.Methodsthis was a prospective cross-sectional study. Consecutive 77 hypertensive subjects were studied using Schiller MT-300 for 24-h ABPM.Resultsout of the 77 patients reviewed, 39 (50.6%) were females. The mean age was 50.9 years (SD 13.5). The mean awake systolic and diastolic BP were 135.6mmHg (SD 15.0) and 83.2mmHg (SD 10.0) respectively; mean asleep systolic and diastolic BP were 127.6mmHg (SD 17.9) and 76.2mmHg (SD 12.2) respectively; and mean 24-h systolic and diastolic BP were 133.6mmHg (SD 15.3) and 81.4mmHg (SD 10.2) respectively. Awake BP was elevated in 59.7% of study subjects. Elevated awake systolic BP and awake diastolic BP were present in 50.6% and 41.6% of the study population. Nocturnal (asleep) BP was elevated in 79.2%. Non-dipping pattern was the most prevalent pattern at 55.8%, followed by dipping (24.7%), reverse dipping (15.6%) and extreme dipping (3.9%).Conclusiona high proportion had nocturnal hypertension (79.2%) and non-dipping pattern was the most prevalent pattern (55.8%). Mean awake systolic BP, mean asleep systolic and diastolic BP and mean 24-h systolic and diastolic BP were elevated. The use of 24-h ABPM will enhance assessment of increased cardiovascular risk and management of Nigerians with hypertension.

Chronological Delivery of Antihypertensive Drugs in Bilayered Core-in-Cup Buccoadhesive Tablets: In Vitro and In Vivo Evaluation.

Hypertension shows circadian blood pressure rhythms (day-night pattern) that urge the delivery of antihypertensive drugs at the right time in the desired levels. Thus, a bilayered core-in-cup buccoadhesive tablet was formulated that immediately releases olmesartan, to give a burst effect, and controls azelnidipine release, to prolong its therapeutic effect. The main challenge was the poor bioavailability of azelnidipine due to its poor aqueous solubility and first-pass effect. Hence, liquisolid compact buccoadhesive tablets were prepared to enhance solubility, dissolution profiles, and bypass the oral route. Two factorial designs were conducted to study the type and concentration effect of the mucoadhesive polymers on the dissolution and mucoadhesion of olmesartan and azelnidipine. Characterization studies were conducted regarding drug content, surface pH, water uptake, mucoadhesive strength, in vitro release, and ex vivo permeability. The core-in-cup olmesartan/azelnidipine buccoadhesive tablet showed similar release profile to the statistically optimized formulae of each drug. In vitro dissolution study showed enhanced release of azelnidipine than the directly compressed tablets, to comply with the regulatory standards of controlled release systems. In vivo pharmacokinetic study of olmesartan and azelnidipine conducted on human volunteers against Rezaltas® 10/8mg tablet showed percentage relative bioavailability of 106.12 and 470.82%, respectively. Graphical Abstract.

The effect of three-component antihypertensive treatment on the structural and functional state of the heart and daily blood pressure profile in patients with hypertension grade 3

Aim. To study the effect of a fixed combination of perindopril arginine (10 mg) + indapamide (2.5 mg) + amlodipine (5 mg) on the daily profile of blood pressure and the structural and functional state of the heart in patients with hypertension grade 3.&#x0D; Methods. 80 patients with hypertension receiving various variants of treatment [50 patients (experimental group) receiving fixed combination of perindopril arginine (10 mg) + indapamide (2.5 mg) + amlodipine (5 mg) and 30 patients (control group) receiving combination of lisinopril with hydrochlorothiazide (10/12.520/25 mg) and amlodipine (5 mg)] underwent electrocardiography, Doppler echocardiography, daily monitoring of blood pressure at there points: at the beginning, after 2 weeks and 6 months of the treatment. Statistical significance of the indicators was determined by Students t-test. To compare the double changes, 2 was used. Statistical difference between the groups was considered significant if p 0.05.&#x0D; Results. In 86% of patients from the experimental group, a decrease in systolic blood pressure by 20 mm Hg or more and/or diastolic blood pressure by 10 mm Hg was noted, which persisted for 6 months. After 6 months of treatment, according to daily monitoring of arterial pressure, the average daily systolic and diastolic blood pressure significantly decreased by 15.9 and 18.6% (р 0.001), and the values of variability of average systolic and average diastolic pressure at night and daytime by 4 and 4.2%, respectively (р 0.001). A decrease in the morning rise rate of systolic and diastolic blood pressure was also achieved (р 0.001). During treatment, a number of patients with a daily curve of the dipper type increased due to a decrease in non-dippers and night pickers (р 0.001).&#x0D; Conclusion. Positive antihypertensive result after treatment with a combination of perindopril arqinine + indapamide + amlodipin was achieved in the early stages of treatment and was observed as a long-term stable hypotensive effect; a number of patients with normal daily rhythm of blood pressure increased, decrease of the severity of hypertrophy and size of the left ventricle was observed and its diastolic function became normal.

Valsartan-mediated chronotherapy in spontaneously hypertensive rats via targeting clock gene expression in vascular smooth muscle cells

Objective This study was to investigate the underlying mechanisms of valsartan chronotherapy in regulating blood pressure variability. Methods RT-PCR was used to assay clock genes expression rhythm in the hypothalamus, aortic vessels, and target organs after valsartan chronotherapy. WB was used to measure Period 1 (Per1), Period 2 (Per2) protein expression in aortic vessels, as well as to measure phosphorylation of 20-kDa regulatory myosin light chain (MLC20) in VSMCs. Results Specific clock genes in the hypothalamus, and Per1 and Per2 in aorta abdominalis, exhibited disordered circadian expression in vivo. Valsartan asleep time administration (VSA) restored circadian clock gene expression in a tissue- and gene-specific manner. In vitro, VSA was more efficient in blocking angiotensin II relative to VWA, which led to differential circadian rhythms of Per1 and Per2, ultimately corrected MLC20 phosphorylation. Conclusion VSA may be efficacious in regulating circadian clock genes rhythm, then concomitantly correct circadian blood pressure rhythms.

Alterations of the cardiovascular rhythms and sleep quality in esophageal cancer patients

ABSTRACT In humans, there is a daily rhythm in blood pressure and is one of the known risk factors for different types of cardiovascular diseases. Sleep quality is an important clinical construct. Daytime sleepiness is common sleep related clinical problem, suggesting a serious underlying physiological anomaly. Most of the studies have been done in reference to colorectal/rectal cancer however, limited knowledge is available for other cancer patients. Present study was conducted on esophageal cancer patients (N= 24; 10 male and 14 female). Daily activity rest pattern using actigraphy and cardiovascular parameters were recoded using ABPM. Sleep quality and daytime sleepiness was studied using the Pittsburgh Sleep Quality Index (PSQI) and Epworth sleepiness scale (ESS) respectively. Our results show that there is daily variation in activity rest pattern and cardiovascular parameters (systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse and double product) in both healthy subjects and esophagealcancer patients but with reduction in the amplitude of cardiovascular parameters in patients without affecting activity rest pattern. Sleep quality is also compromised and daytime sleepiness is higher in cancer patients. The study show that cardiovascular parameters and sleep quality is altered in the esophageal cancer patients.

Structure of Rhythms of Blood Pressure, Heart Rate, Excretion of Electrolytes, and Secretion of Melatonin in Normotensive and Spontaneously Hypertensive Rats Maintained under Conditions of Prolonged Daylight Duration.

We studied the structure of rhythms of BP, HR (by telemetric monitoring), electrolyte excretion (by capillary electrophoresis), and products of epiphyseal melatonin (by the urinary concentration of 6-sulfatoxymelatonin measured by ELISA) in normotensive Wistar-Kyoto rats and spontaneously hypertensive SHR rats maintained at 16/8 h and 20/4 h light-dark regimes. In Wister-Kyoto rats exposed to prolonged daylight, we observed changes in the amplitude, rhythm power (% of rhythm), and range of oscillations of systolic BP; HR mezor decreased. In SHR rats, mezor of HR also decreased, but other parameters of rhythms remained unchanged. Changes in electrolyte excretion were opposite in normo- and hypertensive rats. Under conditions of 20/4 h light-dark regime, daytime melatonin production tended to increase in normotensive rats and significantly increased in SHR rats. At the same time, nighttime melatonin production did not change in both normotensive and hypertensive animals. As the secretion of melatonin has similar features in animals of both lines, we can say that the epiphyseal component of the "biological clock" is not the only component of the functional system that determines the response of the studied rhythms to an increase in the duration of light exposure.