Small Changes In Blood Pressure Research Articles

Comprehensive Management of Blood Pressure in Patients with Septic AKI.

Acute kidney injury (AKI) is one of the serious complications of sepsis in clinical practice, and is an important cause of prolonged hospitalization, death, increased medical costs, and a huge medical burden to society. The pathogenesis of AKI associated with sepsis is relatively complex and includes hemodynamic abnormalities due to inflammatory response, oxidative stress, and shock, which subsequently cause a decrease in renal perfusion pressure and eventually lead to ischemia and hypoxia in renal tissue. Active clinical correction of hypotension can effectively improve renal microcirculatory disorders and promote the recovery of renal function. Furthermore, it has been found that in patients with a previous history of hypertension, small changes in blood pressure may be even more deleterious for kidney function. Therefore, the management of blood pressure in patients with sepsis-related AKI will directly affect the short-term and long-term renal function prognosis. This review summarizes the pathophysiological mechanisms of microcirculatory disorders affecting renal function, fluid management, vasopressor, the clinical blood pressure target, and kidney replacement therapy to provide a reference for the clinical management of sepsis-related AKI, thereby promoting the recovery of renal function for the purpose of improving patient prognosis.

Association between the Change in Blood Pressure during Normotensive Pregnancy and the Development of Hypertension in Later Life.

Women who experience maternal complications, including pre-eclampsia, have a higher risk of cardiovascular disease development. Although the mechanism remains unclear, there is a hypothesis that pregnancy would be a stress test for cardiovascular disease. This study aimed to investigate whether changes in blood pressure during pregnancy would be associated with developing hypertension, which is a main risk of cardiovascular disease. We conducted a retrospective study by collecting Maternity Health Record Books from 735 middle-aged women. Of these, 520 women were selected based on our criteria. 138 were defined as the hypertensive group according to the criteria of receiving antihypertensive medications or blood pressures of >140/90 mmHg at the survey. The rest 382 were defined as the normotensive group. We compared the blood pressures of the hypertensive group with those of the normotensive group during pregnancy and postpartum. Then, 520 women were divided into quartiles (Q1-Q4) according to their blood pressures during pregnancy. After the changes in blood pressure for each gestational month relative to nonpregnant measurements were calculated, the changes in blood pressure were compared among the four groups. Additionally, the rate of developing hypertension was evaluated among the four groups. The average age of the participants was 54.8 years (range: 40-85 years) at the time of the study and 25.9 years (range: 18-44 years) at delivery. There were significant differences in blood pressure during pregnancy between the hypertensive group and the normotensive group. Meanwhile, these two groups did not indicate any differences in blood pressure in postpartum. Higher mean blood pressure during pregnancy was associated with smaller changes in blood pressure during pregnancy. The rate of development of hypertension in each group of systolic blood pressure was 15.9% (Q1), 24.6% (Q2), 29.7% (Q3), and 29.7% (Q4). The rate of development of hypertension in each group of diastolic blood pressure (DBP) was 18.8% (Q1), 24.6% (Q2), 22.5% (Q3), and 34.1% (Q4). Changes in blood pressure during pregnancy are small in women who have a higher risk of hypertension. Levels of blood pressure during pregnancy may be reflected in individual stiffness of blood vessels by the burden of pregnancy. If so, levels of blood pressure would be used to facilitate highly cost-effective screening and interventions for women with a high risk of cardiovascular diseases.

Effects of Oral Testosterone Undecanoate (Kyzatrex) Versus Testosterone Gel (Androgel) on Long-Term (to 12 Months) Blood Pressure Levels

Purpose: Oral and injectable testosterone replacement therapies have been reported to increase blood pressure (BP) in hypogonadal men. Less is known about the effects of topical testosterone formulations on BP. Materials and Methods: We studied the effects of a new oral testosterone undecanoate (TU) (Kyzatrex™) and a topical testosterone gel (Androgel™) on BP and heart rate, in a 2:1 randomized trial of men with hypogonadism. Digital BPs and clinical assessments were obtained at baseline and at 90, 180 and 365 days. Results: There were 314 men randomized (mean age 49.7 years, 82% white, and 35% with treated hypertension). The mean changes from baseline in systolic BP were 2.2 mmHg (95% confidence interval [CI] 0.6–3.7) on the oral TU and 3.1 mmHg (95% CI 1.0–5.1) on the topical testosterone at 90 days. Similar findings were seen after 180 and 365 days. Heart rate increased by 4.3 and 2.7 beats/min at 90 days on oral and topical testosterone, respectively. For those men with treated hypertension, changes in systolic BP in the oral TU group were higher compared with those without hypertension, whereas those on topical testosterone had similar increases in systolic BP regardless of hypertension status. Outlier analyses for systolic BP at 90 days demonstrated a higher proportions of subjects with increases of 5 and 10 mmHg postbaseline on topical testosterone gel versus this oral TU. Conclusions: These data demonstrate that the overall effects of the oral TU on BP were comparable with a topical testosterone. In men without hypertension, the oral TU induced smaller changes in BP compared with topical testosterone. Clinical Trial Registration (https://www.clinicaltrials.gov/): NCT04467697.

Effects of daily walking on office, home and 24-h blood pressure in hypertensive patients

Aerobic exercise has been recommended in the management of hypertension. However, few studies have examined the effect of walking on ambulatory blood pressure (BP), and no studies have employed home BP monitoring. We investigated the effects of daily walking on office, home, and 24-h ambulatory BP in hypertensive patients. Sixty-five treated or untreated patients with essential hypertension (39 women and 26 men, 60 ± 9 years) were examined in a randomized cross-over design. The patients were asked to take a daily walk of 30–60 min to achieve 10 000 steps/d for 4 weeks, and to maintain usual activities for another 4 weeks. The number of steps taken and home BP were recorded everyday. Measurement of office and ambulatory BP, and sampling of blood and urine were performed at the end of each period. The average number of steps were 5349 ± 2267/d and 10 049 ± 3403/d in the control and walking period, respectively. Body weight and urinary sodium excretion did not change. Office, home, and 24-h BP in the walking period were lower compared to the control period by 2.6 ± 9.4/1.3 ± 4.9 mmHg (p < 0.05), 1.6 ± 6.8/1.5 ± 3.7 mmHg (p < 0.01), and 2.4 ± 7.6/1.8 ± 5.3 mmHg (p < 0.01), respectively. Average 24-h heart rate and serum triglyceride also decreased significantly. The changes in 24-h BP with walking significantly correlated with the average 24-h BP in the control period. In conclusion, daily walking lowered office, home, and 24-h BP, and improved 24-h heart rate and lipid metabolism in hypertensive patients. However, the small changes in BP may limit the value of walking as a non-pharmacologic therapy for hypertension.

Haemodynamic Assessment in Safety Pharmacology.

Evaluation of the effects of a drug on arterial blood pressure is important in nonclinical safety pharmacology assessment. Detecting large and obvious changes in blood pressure is an unchallenging task. Detecting small changes is more difficult, and interpretation of findings requires careful risk/benefit evaluation. Detecting subtle and small changes in blood pressure is important in particular with respect to increases, since blood pressure above the normal range is associated with increased risk of stroke and sudden cardiac death. Cardiovascular safety pharmacology has been preoccupied with drug-induced changes in the electrocardiogram, and by comparison, there has been little in the way of contemporaneous improvements in the level of complexity and sophistication involved in blood pressure assessment. Thus, it is important to understand the nature of drug-induced changes in blood pressure, appreciate the plethora of agents currently used clinically (and over the counter) that alter blood pressure and understand safety pharmacology study design in order to optimize assessment of a new chemical entity (NCE) or biologic agent in this context.

Renal nerves: time for reassessment of their role in hypertension?

Renal nerves: time for reassessment of their role in hypertension?

Abstract 562: Differential Effects of Renin Inhibitors and Ca2+ Channel Blockers on Blood Pressure and Vascular Function in Caveolin-1 Null Mice

Caveolin-1 (cav-1) is a transmembrane protein identified in plasma membrane caveolae, and a potential modulator of renal and vascular function and insulin sensitivity. We have shown that cav-1 gene variants are associated with insulin resistance (IR) in hypertensive humans, and that cav-1 deficiency in mice leads to increased blood pressure (BP) and IR. To test whether these changes in the cav-1 KO involve renal or vascular abnormalities, we treated WT and cav-1 KO mice for 14 days with placebo, the renin inhibitor aliskiren (50 mg/kg/day), or the Ca 2+ channel blocker amlodipine (6 mg/kg/day) and assessed BP, fasting blood glucose, HOMA-IR, plasma aldosterone (ALDO), and vascular function. Cav-1 KO mice, as compared with WT, showed increased BP (131±7 vs. 110±2 mm Hg), blood glucose (112±4 vs. 83±4 mg/dl), HOMA-IR (1.9±1.1 vs. 1.1±0.4), lower plasma ALDO (97±10 vs. 131±42 ng/dl), and altered vascular reactivity--reduced Phe-induced vasoconstriction (0.6±0.2 vs. 1.1±0.2g), enhanced acetylcholine (ACh)-induced relaxation (65±11 vs 23±7%), and enhanced relaxation in response to exogenous NO. Endothelium removal, NOS inhibition, or guanylate cyclase inhibition abolished ACh-induced relaxation, suggesting changes in endothelium-dependent NO-cGMP pathway in cav-1 KO mice. In cav-1 KO mice aliskiren significantly reduced BP to 113±4 mm Hg, ALDO levels by 40%, and HOMA-IR to 0.9±0.1, but had no significant effects on blood glucose, Phe-induced vasoconstriction, ACh- or exogenous NO-induced vasorelaxation. In contrast, amlodipine reduced BP to 117±4 mmHg (this effect did not reach significance), had no effect on ALDO levels, and showed a trend for increased IR. Importantly, amlodipine enhanced the sensitivity to Phe in both WT and cav-1 KO, and reduced the ACh-induced relaxation in cav-1 KO mice to 47±11%. Thus aliskiren treatment in cav-1 KO mice reduced BP possibly through suppression of RAAS and improved insulin sensitivity, but did not affect vascular function. In contrast, amlodipine treatment showed small changes in BP and IR but had adverse effects on vascular reactivity in cav-1 KO mice, raising the concern that it could have similar adverse effects on vascular function in hypertensive individuals that carry the cav-1 minor allele gene variants.

Association between blood pressure and DNA methylation of retrotransposons and pro-inflammatory genes

Methylation of deoxyribonucleic acid (DNA) is an epigenetic regulator of gene expression that changes with age, but its contribution to aging-related disorders, including high blood pressure (BP), is still largely unknown. We examined the relation of BP to the methylation of retrotransposon sequences of DNA and of selected candidate genes. This investigation included 789 elderly participants in the Normative Aging Study, ranging in age from 55 to 100 years, who had longitudinal measurements of DNA methylation. In these subjects' DNA we measured the proportion of methylated sites in retrotransposable sequences and in pro-inflammatory genes, expressed as the percent of 5-methylated cytosines (%5mC) among all cytosines. From one to four methylation measurements were made for each subject between 1999 and 2009. We fit mixed-effects models, using repeated measures of BP as the outcome and DNA methylation as the explanatory variable, adjusting for confounding variables. We also fit a Bayesian mixed-effects structural equation model to account for heterogeneity in the effects of methylation sites within each gene. An increase in inter-quartile range (IQR) in the methylation of Alu elements was associated with an increase of 0.97 mm Hg in diastolic blood pressure (DBP) (95% CI 0.32-1.57), but no such association was observed for long interspersed nuclear element-1 (LINE-1). We also found positive associations between DBP and methylation of the genes for toll-like receptor 2 (TLR2) and inducible nitric oxide synthase (iNOS), and a negative association between DBP and methylation of the gene for interferon-γ (IFN-γ). Associations between methylation and systolic blood pressure (SBP) were weaker than those between methylation and DBP. Bayesian mixed-effects structural equation model results were similar for both DBP and SBP models. The results of our study suggest that changes in DNA methylation of some pro-inflammatory genes and retrotransposable elements are related to small changes in BP.

Comparison of non-invasive and implanted telemetric measurement of blood pressure and electrocardiogram in conscious beagle dogs

IntroductionThe objective of this study was to evaluate the ability of a non-invasive telemetry monitoring system to detect and quantify changes in blood pressure and electrocardiogram (ECG) parameters in response to vehicle, l-NAME or minoxidil administration to freely moving beagle dogs. Data from a non-invasive telemetry monitoring system were compared to data captured from an invasive telemetry implant in the same animals. MethodsBlood pressure and ECG data were simultaneously acquired from male dogs using a non-invasive and an invasive implanted telemetry system for 2hours predose and 24hours post dosing with vehicle (n=5), minoxidil at 1mg/kg (n=4) and L-NAME at 10mg/kg (n=5) on separate test days. Values for mean blood pressure, systolic blood pressure, diastolic blood pressure, pulse pressure, heart rate, RR, PR, QRS, QT and QTcL (heart rate corrected QT interval) interval were reported for both methods. ResultsStatistically significant reductions in blood pressure and pulse pressure and increases in heart rate, with associated ECG interval changes were apparent following dosing with minoxidil using both methods. Statistically significant increases in blood pressure and pulse pressure were apparent following dosing with l-NAME when using the invasive telemetry system, changes were apparent when using the non-invasive telemetry system, however, no change was apparent for pulse pressure, they were of shorter duration and not statistically significant. Statistically significant decreases in heart rate, with associated changes in ECG intervals, were apparent following treatment with l-NAME for both invasive and non-invasive methods. DiscussionThis study shows that the non-invasive system can be successfully used to acquire both ECG and blood pressure data in freely moving jacketed dogs for at least 26hours, yet requires further technique refinement to improve system sensitivity to detect smaller changes in blood pressure.

Hydroxyfasudil Ameliorates Bladder Dysfunction in Male Spontaneously Hypertensive Rats

To investigate the effect of hydroxyfasudil, a nonselective Rho-kinase inhibitor, on hypertension-related bladder dysfunction in spontaneously hypertensive rats (SHRs), as there is an increasing evidence that the Rho-associated protein kinase (ROCK) system plays an important role in bladder contraction. Twelve-week-old male SHRs were treated with hydroxyfasudil (1 mg/kg i.p.) once a day for 6 weeks. Wistar rats and SHRs without treatment with hydroxyfasudil were used as controls. Six weeks after the hydroxyfasudil treatment, voiding functions were evaluated by metabolic cages and cystometric studies under urethane anesthesia (1.0 g/kg i.p.). Bladder blood flow (BBF) was estimated by the hydrogen clearance method. The bladder tissue levels of nerve growth factor (NGF) and ROCK activity were evaluated by the ELISA method. The SHR showed significant increases in micturition frequency and decreases in single-voided volume in metabolic cages, and significantly increases in micturition frequency and intercontractile interval in cystometric studies. Furthermore, the SHR showed significant increases in the BBF and bladder NGF concentration compared with the Wistar rats. These alterations in the SHR were significantly ameliorated after treatment with hydroxyfasudil, with small changes in blood pressure. However, the maximum detrusor pressures during voiding and the ROCK activities in the experimental bladders were similar in all rats examined. Our data indicate that this dose of hydroxyfasudil was effective on the BBF, whereas it had no significant effect on micturition pressure. These findings suggest that hydroxyfasudil could ameliorate hypertension-related bladder dysfunction in the SHR via improvement of the BBF (248 words).

In vivo assessment of artery smooth muscle [Ca2+]i and MLCK activation in FRET-based biosensor mice

The cellular mechanisms that control arterial diameter in vivo, particularly in hypertension, are uncertain. Here, we report a method that permits arterial intracellular Ca(2+) concentration ([Ca(2+)](i)), myosin light-chain kinase (MLCK) activation, and artery external diameter to be recorded simultaneously with arterial blood pressure (BP) in living mice under 1.5% isofluorane anesthesia. The method also enables an assessment of local receptor activity on [Ca(2+)](i), MLCK activity, and diameter in arteries, uncomplicated by systemic effects. Transgenic mice that express, in smooth muscle, a Ca(2+)/calmodulin-activated, Förster resonance energy transfer (FRET)-based "ratiometric", exogenous MLCK biosensor were used. Vasoactive substances were administered either intravenously or locally to segments of exposed femoral or cremaster arteries. In the basal state, mean BP was approximately 90 mmHg, femoral arteries were constricted to 65% of their passive diameter, MLCK fractional activation was 0.14, and [Ca(2+)](i) was 131 nM. Phenylephrine (300 ng/g wt iv) elevated mean BP transiently to approximately 110 mmHg, decreased heart rate, increased femoral artery [Ca(2+)](i) to 244 nM and fractional MLCK activation to 0.24, and decreased artery diameter by 23%. In comparison, local application of 1.0 muM phenylephrine raised [Ca(2+)](i) to 279 nM and fractional MLCK activation to 0.26, and reduced diameter by 25%, but did not affect BP or heart rate. Intravital FRET imaging of exogenous MLCK biosensor mice permits quantification of changes in [Ca(2+)](i) and MLCK activation that accompany small changes in BP. Based on the observed variance of the FRET data, this method should enable the detection of a difference in basal [Ca(2+)](i) of 29 nM between two groups of 12 mice with a significance of P < 0.05.

Beneficial effects of rosuvastatin on aortic adverse remodeling in nitric oxide-deficient rats

This study aimed to evaluate the effect of rosuvastatin upon structural and ultrastructural aortic remodeling in a rat model of hypertension induced by NO synthase blockade. Wistar rats were divided into 4 groups: Control group (C); control treated with rosuvastatin 20 mg/kg/day (CR); L-NAME group 40 mg/kg/day (LN) and L-NAME treated with rosuvastatin (LNR) (same doses). Body mass and blood pressure were measured weekly; the experiment lasted 5 weeks. L-NAME administration augmented blood pressure (BP) in the LN group in comparison to the C group (123.3 vs. 180.5 mmHg at week 5). In LNR rats, rosuvastatin slightly attenuated BP rise, but it had no effect on the BP of CR group. Intima and media thickening of the thoracic aorta were observed in the LN group, and increased elastic fiber content as well. Rosuvastatin prevented all these alterations as seen in the LNR group. Ultrastructural changes due to L-NAME intake (intracellular vesicles and altered membrane morphology in endothelial cells, extracellular matrix deposition, and cytoplasmatic projections from smooth muscle cells toward the internal elastic lamina) were also prevented by rosuvastatin. All in all, rosuvastatin administration is capable of attenuating ultrastructural aortic wall remodeling in NO-deficient rats despite small changes in blood pressure.

Salt intake, blood pressure and clinical outcomes

Purpose of review Salt intake has long been known to influence blood pressure among hypertensive patients, but its effect among those without overt hypertension, as well as its effects on cardiovascular disease itself, have been disputed. This report reviews the evidence for an effect on both blood pressure and cardiovascular disease, particularly among normotensive participants, including recent data from randomized trials. Recent findings The Dietary Approaches to Stop Hypertension study provided clear evidence for a short-term effect of sodium on blood pressure among those with and without hypertension. Longer term trials among nonhypertensive particpants suggest more modest effects of lifestyle sodium reduction interventions on blood pressure. The recent Trials of Hypertension Prevention follow-up study found that, despite small changes in blood pressure, the risk of cardiovascular disease was reduced by 25% among those in the sodium reduction intervention. A study of potassium salt substitution among Taiwanese veterans supports this finding. Sodium and potassium may act jointly in the development of hypertension and cardiovascular disease. Summary Average sodium consumption in the US population is excessively high, and well above recommended limits. Because most sodium derives from processed and restaurant foods, a reduction of sodium in these sources, as recently called for by the American Medical Association, is necessary to reduce exposure.

A Comparison of the Blood Pressure Changes of Lumiracoxib With Those of Ibuprofen and Naproxen

The 52-week Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) investigated the gastrointestinal and cardiovascular safety profile of lumiracoxib 400 mg once daily compared with 2 traditional nonsteroidal anti-inflammatory drugs (NSAIDs): ibuprofen 800 mg 3 times daily and naproxen 500 mg twice daily. Data from TARGET were analyzed to examine the effect of lumiracoxib compared with ibuprofen and naproxen on blood pressure (BP), incidence of de novo and aggravated hypertension, prespecified edema events, and congestive heart failure. Lumiracoxib resulted in smaller changes in BP as early as week 4. Least-squares mean change from baseline at week 4 for systolic BP was +0.57 mm Hg with lumiracoxib compared with +3.14 mm Hg with ibuprofen (P<.0001) and +0.43 with lumiracoxib compared with +1.80 mm Hg with naproxen (P<.0001). In conclusion, the use of lumiracoxib and traditional NSAIDs results in differing BP changes; these might be of clinical relevance.

Salt intake, blood pressure and clinical outcomes

Salt intake has long been known to influence blood pressure among hypertensive patients, but its effect among those without overt hypertension, as well as its effects on cardiovascular disease itself, have been disputed. This report reviews the evidence for an effect on both blood pressure and cardiovascular disease, particularly among normotensive participants, including recent data from randomized trials. The Dietary Approaches to Stop Hypertension study provided clear evidence for a short-term effect of sodium on blood pressure among those with and without hypertension. Longer term trials among nonhypertensive particpants suggest more modest effects of lifestyle sodium reduction interventions on blood pressure. The recent Trials of Hypertension Prevention follow-up study found that, despite small changes in blood pressure, the risk of cardiovascular disease was reduced by 25% among those in the sodium reduction intervention. A study of potassium salt substitution among Taiwanese veterans supports this finding. Sodium and potassium may act jointly in the development of hypertension and cardiovascular disease. Average sodium consumption in the US population is excessively high, and well above recommended limits. Because most sodium derives from processed and restaurant foods, a reduction of sodium in these sources, as recently called for by the American Medical Association, is necessary to reduce exposure.

Cardiovascular responses to the change from the left lateral to the upright position in pregnant hypertensives

Objective: To evaluate by non-invasive means, the autonomically mediated changes in heart rate and blood pressure in response to postural change in pregnancy. Method: Ninety-one patients were studied, of whom 17 were non-pregnant controls, 21 were normotensive parturients, 22 had non-proteinuric hypertension, and 31 were pre-eclamptics. In all patients the heart rate and blood pressure response to the change from the left lateral to the erect position was measured non-invasively, during the third trimester in the pregnant groups. Results: The change from the left lateral to the erect position induced significantly greater mean changes (increases) in systolic blood pressure in the normotensive pregnant (PC) women than all other groups ( P<0.05). Pre-eclamptic patients (PE) exhibited significantly less of an increase in systolic blood pressure than the non-proteinuric hypertensive (H) group. Both the H and PC groups showed significantly greater increases in diastolic pressure than the non-pregnant (NP) group. PE patients had a significantly smaller increase in diastolic pressure than the H group. There were no significant differences between heart rate changes when comparing the PC, NP and H groups. The PE group exhibited a significantly greater increase in heart rate on adopting the erect position than all other groups. Conclusions: Pre-eclamptics exhibit smaller changes in blood pressure than normotensive pregnant patients and non-proteinuric hypertensives on standing, while producing an exaggerated heart rate response, indicating altered autonomic compensatory mechanisms in these patients.

Trends in blood pressure, lipids, lipoproteins and glucose metabolism in the Northern Sweden MONICA project 1986 - 99

The authors present an analysis of time trends in blood pressure, hypertension, and lipids in the adult population of Northern Sweden over the period 1986-99. Four population surveys were undertaken with new and independent cohorts, 25-64 years old. Small changes in blood pressure were observed during the study period with increased systolic blood pressure in men and decreased diastolic blood pressure in women. The proportion with high blood pressure was found to be constant over time and only 50% were prescribed antihypertensive drugs and of these only a minority were normotensive. Total serum cholesterol decreased from 6.4 to 5.7 mmol/l in men and from 6.3 to 5.7 mmol/l in women over the study period, and this was accompanied by an increase in HDL cholesterol by about 10% in both sexes. The proportion with high cholesterol decreased from 41% to 26%. Triglycerides increased between 1986 and 1990 and no further changes were found in the following surveys. In the Northern Sweden MONICA population total cholesterol has declined and HDL cholesterol has increased during the past 13 years and small changes in blood pressure have been observed for both men and women.

Cardiovascular effects of tadalafil

To determine the effects of tadalafil on the cardiovascular system, safety assessments were performed on a database of >4,000 subjects who received tadalafil in >60 clinical pharmacology, phase 2, phase 3, and open-label studies. In healthy subjects, tadalafil resulted in small changes in blood pressure, which are not believed to be clinically relevant. Daily administration of tadalafil 20 mg for 26 weeks in healthy male subjects or patients with mild erectile dysfunction resulted in blood pressure changes similar to those observed after placebo administration. In patients with coronary artery disease (CAD), tadalafil administration before nitrate administration resulted in small decreases in blood pressure. The resulting mean maximal change in standing systolic blood pressure (SBP) after coadministration of sublingual nitroglycerin in patients with chronic stable angina was −36 mm Hg for tadalafil 5 mg, −31 mm Hg for tadalafil 10 mg, and −28 mm Hg for placebo. In addition, a larger number of men had a standing SBP <85 mm Hg after coadministration of sublingual nitroglycerin and tadalafil 5 mg (p <0.001 vs placebo) or tadalafil 10 mg (p <0.01 vs placebo) compared with coadministration with placebo. In patients with chronic stable angina taking doses of isosorbide mononitrate on a long-term basis, the mean maximal change in standing SBP was −23 mm Hg for placebo, −23 mm Hg for tadalafil 5 mg, and −26 mm Hg for tadalafil 10 mg. In a study of older subjects (≥55 years of age) with no overt evidence of CAD, the resulting mean maximal change in standing SBP after coadministration of sublingual nitroglycerin was −25 mm Hg for tadalafil 10 mg, −29 mm Hg for sildenafil 50 mg, and −25 mm Hg for placebo. Cardiac mortality rates in tadalafil studies are consistent with the expected rate in this male population. Across all studies, the incidence rate of myocardial infarction was low in tadalafil-treated patients (0.43 per 100 patient-years) compared with patients who received placebo (0.6 per 100 patient-years), and the incidence rate was comparable to that observed in the age-standardized male population (0.60 per 100 patient-years). The incidence rate of presumed thrombotic strokes in tadalafil studies (0.27 per 100 patient-years) is comparable to the expected rate in this patient population. The data presented herein suggest that tadalafil can be safely used by healthy subjects and by patients with cardiovascular diseases. As with sildenafil, the use of tadalafil is contraindicated in patients receiving nitrate therapy because of the potential for significant hypotensive effects.

Physiological relationship between autonomic reactions and arousals in infancy

Objective: Changes in blood pressure (BP) were measured following auditory stimuli in the prone and the supine position to study the correlation between arousal from sleep and autonomic responses. Method: Two newborns born at term, two infants and four children were recorded polygraphically during one night, while sleeping in the prone and the supine position. They were exposed to white noises of increasing intensities during both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep in each position. BP changes were measured by Finapress in the children and by pulse transient time (PTT) in the infants and newborns. Results: Basal systolic BP pressures were lower ( P<0.001) and PTT were higher ( P=0.008) in the prone than in the supine position in children and in infants. Following the auditory stimulations, the increases in systolic BP ( P=0.024) and the decreases in PTT ( P=0.006) were smaller in prone than in supine position. During cortical arousals, the same findings were found, independently of sleep stages. Conclusion: Compared with when they are sleeping supine, children and infants sleeping prone had lower basal BP and higher PTT and smaller changes in BP and PTT after auditory stimulation. Reduced BP changes to stimuli could be implicated in the increased arousal thresholds in prone position.

Role of blood pressure monitoring in non-pharmacological management of hypertension

Ambulatory blood pressure monitoring (ABPM) and home blood pressure (BP) measurement appear to be useful in the assessment of the effects of non-pharmacological treatment of hypertension because they can detect small changes in BP without observer bias. We studied the effects of various lifestyle modifications using ABPM and home BP measurement in Japanese patients with hypertension. Weight reduction by a hypocaloric diet (average 4 kg) was associated with decreases in 24-h BP (10/4 mmHg) as well as casual BP (9/6 mmHg). The reductions in daytime and night-time BPs were comparable. The effects of daily walking without weight loss on office, home, and 24-h BPs were 2-3/1-2 mmHg. The changes in home and 24-h BPs were more significant than those in office BP. A low-salt diet (25 mmol/day versus 250 mmol/day) decreased 24-h BP by 9/4 mmHg. This hypotensive effect was observed throughout the day. Potassium supplementation (64 mmol/day) decreased office, home and 24-h BPs by 3-4/1-2 mmHg. The changes in home and 24-h BPs were highly significant compared with office BP. Supplementation of magnesium (20 mmol/day) also reduced those BPs significantly. However, the effects of calcium supplementation (25 mmol/day) were small (1-2/1 mmHg) and were significant only for home BP. Alcohol restriction for 4 weeks decreased daytime BP by 3/2 mmHg but increased night-time BP by 4/2 mmHg. Average 24-h BP did not change. Smoking cessation lowered daytime BP without affecting night-time BP. Monitoring of 24-h BP and home BP can detect small changes in BP produced by lifestyle modifications. Ambulatory BP monitoring is particularly suitable in the assessment of changes in lifestyle affecting the circadian pattern of BP such as alcohol consumption and smoking.