Stable Blood Pressure Control Research Articles

Treatment with Sacubitril/Valsartan Effectively Manages Hypertension and Ameliorates Left Ventricular Hypertrophy in Hemodialysis Patients

Introduction: The aim of this study was to investigate the role of sacubitril/valsartan in managing hypertension and cardiac remodeling in patients undergoing hemodialysis. Methods: Hemodialysis patients with stable blood pressure control were enrolled in the study. Sacubitril/valsartan was prescribed to replace previously used angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or other antihypertensive drugs. During a 6-month follow-up period, pre-dialysis blood pressure, routine biochemical markers, and N-terminal pro-brain natriuretic peptide levels were measured. Volume status was assessed using bioelectrical impedance analysis. Endothelial damage was evaluated by measuring asymmetric dimethylarginine expression, while echocardiography and life quality assessed by Short Form-12 Health Survey were conducted at baseline and after treatment. Results: The median daily dose of sacubitril/valsartan in 32 participants was 200 mg, and no obvious adverse reactions were reported. The defined daily dose of other antihypertensive drugs (baseline 2.00 ± 1.18, end point 1.46 ± 1.30, t = 3.216, p = 0.003) reduced significantly. After treatment with sacubitril/valsartan, left ventricular ejection fraction significantly increased from 64.81 ± 8.16% to 67.55 ± 5.85% (t = −4.022, p ≤ 0.001) and the thickness of posterior wall of the left ventricle reduced from 1.05 ± 0.14 cm to 1.00 ± 0.11 cm (t = 2.063, p = 0.048). The interventricular septal thickness (baseline 1.08 ± 0.16 cm, endpoint 1.02 ± 0.12 cm, t = 2.260, p = 0.031) remarkably reduced by the end of follow-up. The tricuspid regurgitation pressure gradient decreased from 28.47 ± 8.26 mm Hg at baseline to 23.79 ± 6.61 mm Hg (t = 2.531, p = 0.020) after treatment. Conclusion: Sacubitril/valsartan effectively manages hypertension in hemodialysis patients and may also independently improve left ventricular hypertrophy and systolic function, regardless of changes in the blood pressure or the volume load.

TIME IN TARGET RANGE OF SYSTOLIC BLOOD PRESSURE AND EGFR SLOPE IN PATIENTS WITH TYPE 2 DIABETES

Objective: Time in target range (TTR) of systolic blood pressure, a novel measure to assess the effect of blood pressure control, is attracting attention in recent European guidelines. However, few studies have explored the renoprotective value of systolic TTR in patients with type 2 diabetes (T2D). Design and method: We used the database of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure (BP) trial, and 4409 eligible participants were enrolled in the present study. The systolic target range for the standard and intensive therapy was defined as 120 to 140 mm Hg and 110 to 130 mm Hg, respectively. Results: After adjustment for covariates, systolic TTR was significantly and positively associated with 2 indices of eGFR slope (P <= 0.0016), regardless of additional adjustment for systolic blood pressure average and variability. The association of systolic TTR and eGFR slope was significantly stronger in CKD patients than those without CKD (P for interaction <=0.044). When TTR was treated as a categorical variable, participants with the highest systolic TTR in the CKD group had a significantly positive association with eGFR slope (P <= 0.00046). Similar results were obtained in the further subgroup analysis. Conclusions: Among patients with diabetes, systolic TTR showed a significant and positive association with eGFR slope, with a stronger association observed in those with CKD. TTR reflects both blood pressure level and stability across blood pressure management, emphasizing the importance of maintaining stable blood pressure control for renoprotection in T2D patients, particularly in those with CKD.

Prevalence of hypertension among travelers and stability of blood pressure control during travel: a cross-sectional descriptive study and prospective cohort study

BackgroundHypertension is a common and important risk factor for cardiovascular disease which is the leading cause of death among the general population and travelers. Data on hypertension among travelers are very limited due to the scarcity of research reports in this specific population. Therefore, this study aimed to determine the prevalence of hypertension among adult travelers and the stability of blood pressure control during international trips using a mobile automated blood pressure device.MethodsThis was a cross-sectional descriptive study conducted at the Thai travel clinic, Hospital for Tropical Diseases in Bangkok, Thailand. All adult travelers completed a questionnaire which included demographic data, medical history, medication use, trip characteristics and hypertension awareness and knowledge. Standard two time blood pressure measurements were performed at the clinic to detect possible undiagnosed hypertension. Travelers with pre-existing hypertension were also invited to monitor their blood pressure level before and during their trip for a total of 14 days by using an automated blood pressure device and reporting the readings back to the study team.ResultDuring July and October 2022, a total of 1,359 adult travelers visited the Thai Travel Clinic before their international trip. The overall prevalence of hypertension was 28.8%, including those with pre-existing hypertension (6.7%) and those with newly diagnosed hypertension (22.2%). Travelers with newly diagnosed hypertension were significantly younger than travelers with pre-existing hypertension (38.5 years vs. 55.6 years, p < 0.001). Eleven travelers agreed to monitor their blood pressure, Most (90.9%, 10/11) had stable blood pressure control during their trip. One participant had > 10 mmHg higher blood pressure during the trip, however this was not clinically significant. All participants remained well, and acute symptoms secondary to hypertension were not reported.ConclusionUp to 28.8% of adult travelers seen in pre-travel consultations had hypertension. Most of them were unaware of their blood pressure condition. Vital signs including blood pressure should be evaluated in all pre-travel visits in order to prevent undiagnosed severe hypertension that might lead to hypertensive crisis.

PS-R02-1: THE HIDDEN HAND BEHIND AN AORTIC DISSECTION CASE

According to the data of WHO, more than 1.1 billion people worldwide suffer from hypertension, which leads to complications such as aortic dissection, acute myocardial infarction, and heart failure seriously threaten human health. Previously, we believed that primary hypertension accounted for 80%-90% of all hypertension, but with the gradual increase in understanding and improvement of detection methods, the understanding of secondary hypertension factors is becoming clearer. Among the secondary hypertension, primary aldosteronism is receiving more and more attention. It is thought that the actual prevalence of primary aldosteronism may account for 30%-50% of hypertension. The dangers of primary aldosteronism are not only in the damage to target organs from blood pressure, but the damage to organs from elevated aldosterone appears much earlier. Early recognition of primary aldosteronism is important to reduce the emergence of complications. We report a case of a patient with aortic dissection with a previous history of thirty years of hypertension, regular medication and stable blood pressure control, who, after a sudden aortic dissection, had laboratory tests suggesting intractable hypokalemia and poor results with potassium supplementation. We further examined aldosterone and renin levels and found that renin levels were significantly lower, with an aldosterone/renin ratio of 72 (reference value: 0–38). Although the patient was not able to standardize medications at the time of examination due to his condition, the ARB, CCB and hydrochlorothiazide medications the patient was on were all elevated for renin. In this case, renin levels remained low and we have reason to believe that the patient could be diagnosed with primary aldosteronism. With this history, we recognize that screening for secondary hypertension is far from adequate, and some scholars believe that less than 1% of hypertensive patients worldwide are currently screened for secondary factors. We believe that screening for secondary hypertensive factors should be performed in all patients with aortic dissection, even whenever there is combined target organ damage in hypertensive patients, regardless of blood pressure values.

Long-Term Impact of Different Triple Combination Antihypertensive Medications on Blood Pressure Control, Metabolic Pattern and Incident Events: Data from the Brisighella Heart Study.

The aim of this study was to comparatively evaluate clinical, laboratory and hemodynamic effects on the long term of different triple combination antihypertensive medications in a well-characterized Italian cohort. We considered the data of a subset of Brisighella Heart Study (BHS) participants who were consecutively evaluated in three epidemiological surveys between 2012 and 2020. For the current analysis, we excluded normotensive subjects, patients treated with <3 or ≥3 antihypertensive drugs without taking angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium-channel blockers (CCB) and/or thiazide/thiazide-like diuretics. The remaining participants were divided into three groups depending on whether they were treated with Perindopril/Amlodipine/Indapamide, ACE-inhibitors (other than perindopril)/CCBs/Thiazide or ARBs/CCBs/Thiazide, either with separate drugs or fixed pill combinations. A further group of age- and sex-matched volunteers was selected as control and included patients receiving other antihypertensive treatments. The long-term (12 years) effects of the different antihypertensive treatments were compared among the pre-defined groups. During the observation period, there was a trend towards increase in both systolic and diastolic blood pressure (BP) in all the investigated subgroups (p for trend <0.05), but in the subgroup of patients treated with Perindopril/Amlodipine/Indapamide, such increase was significantly lower than in the other groups (p < 0.05). The combination treatment with renin-angiotensin system (RAS) modulators, CCBs and thiazide/thiazide-like diuretics was associated with significantly lower diastolic BP (p < 0.05) and more strictly controlled lipid pattern than other triple combination of anti-hypertensive medications. Patients treated with Perindopril/Amlodipine/Indapamide did not experience any age-related increase in serum levels of total cholesterol. Moreover, during the follow up none of them developed type 2 diabetes, nor had a need for a greater number of antihypertensive drugs to improve BP control, mainly because of a more stable BP control. Based on our observations, combination treatment with RAS modulators, amlodipine and thiazides/thiazide-like diuretics is more effective than other triple antihypertensive medications for lowering the diastolic BP and has a better impact on serum lipids. Perindopril/Amlodipine/Indapamide is associated with more protective metabolic profile than any other considered combination antihypertensive medications.

How to Choose the Optimal Single-Pill Combination of the First-Line Antihypertensive Drugs? The Benefits of Amlodipine and Telmisartan Combination

In patients with arterial hypertension (AH), an extremely important measure of the effectiveness of antihypertensive drugs (AHD) is not only a direct decrease in blood pressure (BP), but also its stable control throughout the 24 hours, preventing excessive morning surge and increased BP variability, which in turn are recognized cardiovascular risk factors. Currently, in the vast majority of hypertensive patients, the main antihypertensive therapy approach is using single-pill combinations (SPC) of AHD. Among the first-line combinations for a wide range of patients with AH and no special clinical conditions is amlodipine/telmisartan SPC. Distinctive features of these drugs, on the one hand, are unique pharmacological properties, consisting in an ultra-long antihypertensive effects, superior to other AHD in their classes; and on the other hand, there is an large body of evidence from numerous clinical trials confirming their high antihypertensive and target-organ protective potential as well as excellent capabilities in cardiovascular risk reduction. To assess the AHD effectiveness extent, several parameters have been proposed, of which the most rational and useful is the smoothness index, calculated using the ambulatory blood pressure monitoring data. Smoothness index describes both the degree of BP reduction and its distribution during the monitoring period. This index inversely associates with the changes in BP variability, and has predictive value in relation to the hypertension-mediated organ damage regression during different antihypertensive regimens. Amlodipine/telmisartan SPC has also been studied in many trials, including comparative ones with other AHD. In these works its direct powerful antihypertensive effect and a pronounced beneficial impact on the smoothness index have been proved, demonstrating stable BP control throughout the 24 hours (especially in the most dangerous morning hours), and also a decrease in BP variability. Therefore, amlodipine/telmisartan SPC can effectively reduce cardiovascular risk and improve prognosis in patients with AH.

Current Trends in the Treatment of Hypertension: Focus on Improving Prognosis. The Capabilities of an Amlodipine/Telmisartan Single-Pill Combination

Nowadays, the modern approach to antihypertensive therapy is to prescribe in the most hypertensive patients fixed-dose combinations of antihypertensive drugs as initial therapy. This concept is reflected in the latest revisions of European and Russian guidelines for the management of arterial hypertension (AH). Above mentioned principle is referred as “single-pill combination” strategy and is given high priority in clinical practice with a high evidence level. According to this approach, one of the possible first line single-pill combinations is the combination of an angiotensin II receptor blocker and a calcium channel blocker. In both classes, the reference and the best representatives include, respectively, telmisartan and amlodipine, as a result of broad experience in their practical application and, most importantly, extensive body of evidence regarding to its effectiveness and safety. Both antihypertensive drugs are distinguished by an extra-longstanding antihypertensive effect that exceeds such one of other representatives in their classes, thereby a stable blood pressure control throughout the day is realized, and most importantly, in the early morning hours, that are the most dangerous in terms of adverse cardiovascular and cerebrovascular events. Another important telmisartan and amlodipine characteristics is their targetorgan protective properties, which is realized at all the levels. In addition, telmisartan has a unique ability to activate PPAR-у-receptors and improves the carbohydrate metabolism and lipid profile, which is advantageous in patients with concomitant metabolic syndrome and diabetes mellitus. The telmisartan and amlodipine features and their proven ability to improve prognosis in hypertensive patients served as background for creating a singlepill combination of these antihypertensive drugs, which fully meet with the requirements of current clinical guidelines for AH management and in which these drugs synergistically coupling resulting in more effective blood pressure control, increases the reliability of target-organ protection, and also improves the therapy safety profile.

Highlights of the December issue.

Highlights of the December issue.

Autotransplantation of Solitary Kidney With Renal Artery Aneurysm Treated With Laparoscopic Nephrectomy and Ex Vivo Repair: A Case Report

Introduction Renal artery aneurysms (RAA) are extremely rare clinical entities with associated morbidities including hypertension and rupture. Although most RAA can be treated with in vivo repair or endovascular techniques, these may not be possible in patients with complex RAA beyond the renal artery bifurcation. We report a case of RAA in a patient with a solitary kidney that we treated successfully by extracorporeal repair and autotransplantation and the 2-years follow-up. Case Report A 64-year-old woman with a history of right nephrectomy for renal cell carcinoma presented with RAA found on routine computed tomography (CT). Preoperative workup demonstrated a 2.2 × 2.1 × 3-cm aneurysm in the distal left renal artery that was not amendable to in vivo or endovascular repair. The patient underwent a laparoscopic-assisted left nephrectomy, ex vivo renal artery aneurysm repair, and autotransplantation. She did well postoperatively and in clinic follow-up was found to have a creatinine of 1.2 mg/dL at the end of 2 years and stable blood pressure control. Discussion This patient with RAA in her solitary kidney was successfully treated with laparoscopic-assisted nephrectomy, ex vivo repair, and autotransplantation. Her creatinine was stable postoperatively despite absence of a second kidney.

Budget impact analysis of use of aliskiren in hypertension on the Italian Health Care System

Cardiovascular (CV) disease management and prevention has been the leading cost driver in health care expenditures of industrialized Countries for many years, and this trend is not expected to change in the next future. Although drugs used for the treatment of arterial hypertension and heart failure account for three fourths of the total Italian pharmaceutical expenditures in this disease area, population studies indicate that only about half of all hypertensive patients are treated for this condition, and that, among treated individuals, only a minority achieves a satisfactory and stable blood pressure control. A complementary observation is that drug expenditures, as high as they seem to be, actually account for only about a fourth of the total direct cost of CV illness, as they are exceeded by costs of hospitalizations required for the acute management of the clinical events that should be, at least partially, prevented by the same cardiovascular drugs. An often pointed out corollary to these findings is that an increase in the rate of controlled hypertension in the population, although surely linked to a further increase in pharmaceutical expenditures, carries the potential to reduce overall health care costs for the management of CV patients. As far as drug treatment is concerned, there seem to be three applicable strategies capable of increasing blood pressure control rates, i.e. interventions directed toward the increase of the treated population, interventions aimed at improving compliance, and the introduction of innovative drugs to cover unmet needs. Aliskiren is the first agent of the new direct renin inhibitors drug class, and has been recently approved in Italy under strict reimbursement restrictions. In this paper, the Authors present a budget impact analysis in the perspective of the National Health Service, conducted by estimating eligible populations according to reimbursement limitations, calculating differential costs by patient subgroups and possible strategies (addition to vs substitution of ACE-Is or ARBs), and finally by applying expected market shares to the identified population. The low forecast market penetration (0.2% and 0.6% of eligible patients, in the first and second year, respectively) drives the results: the treatment of 3,274-9,821 patients induces a yearly increase of 1.5 to 4.5 million € with aliskiren added to ACE-Is or ARBs, and of 917,000 to 2,751,000 € in the substitution scenario.

Long-Term Therapy with Nifedipine-CR Improves Arterio-Sclerosis Related Markers in Patients with Untreated Essential Hypertension

Increased arteriosclerosis is associated with high risk of cardiovascular events. Several non-invasive markers for arteriosclerosis have been introduced, such as pulse wave velocity (PWV), augmentation index (AI), and carotid prop- erties assessed by echogram, to estimate the current risk and therapeutic merit of antihypertensives. In this study, 17 hy- pertensive patients were treated with nifedipine-CR alone for one year, and the non-invasive markers were simultaneously monitored every 3 months. Nifedipine-CR treatment achieved stable blood pressure control, and PWV and AI improved in parallel with the blood pressure. Interestingly, the elastic property of the carotid artery progressively decreased and there was a significant difference between the results at 3 and 12 months (85.8 ± 6.1 vs 72.4 ± 5.0 kPa, P = 0.009). In- tima-media thickness of the carotid artery also decreased. In conclusion, nifedipine-CR demonstrated a stable anti-sclerotic quality in hypertensive patients and seems to be prominent in large arteries such as the carotid.

To be or not to be … hypertensive: That is the question

‘Measure what is measurable and make measurable what is not so’. Galileo's dictum may easily be applied to the history of the measurement of blood pressure – the force at the point of measurement (usually in mmHg) within the cardiovascular system (i.e. the pressure exerted by the blood on the wall of the blood vessel). Blood pressure (BP) is created through the opposing forces generated by the pumping of the heart – within a closed circulatory system – against the resistance offered by the peripheral vasculature. The first recorded measurement of BP in an animal (a horse in 1733) required a brass pipe being directly inserted into a major artery (by the Rev Stephen Hales). Thankfully, techniques for blood pressure measurement have been refined but invasive cannulation remains the gold standard (e.g. radiotelemetry). Non-invasive sphygmomanometry (developed ∼1881) had much greater clinical application and very soon it was clear that the blood pressure distribution in a given population was normal (Gaussian), where a defined rightward shift identified individuals as being ‘hypertensive’, i.e. a statistical term denoting a significant shift away from the median for the population from which the individual was drawn. For man, this shift is ∼20 mmHg (from an optimal systolic blood pressure of 120 mmHg to stage I hypertensive of > 140 mmHg; Verdecchia & Angeli, 2003). Sphygmomanometry was readily applied to animals from rodents (Pfeffer et al. 1971) to horses (Giussani et al. 2003), but has always attracted criticism (Gross & Luft, 2003), due mainly to experimental error or being ‘stressful’ and therefore representing ‘resting’ BP (Tonkiss et al. 1998). Consequently, a number of studies have sought to validate the procedure (e.g. Pfeffer et al. 1971; Bunag, 1973). The paradigm of the developmental origins of health and disease is an active area of research that has brought the methods for measurement of BP into focus and stimulated much related debate. Fourteen years ago it was shown that a maternal low protein (MLP) diet fed to young Wistar rats (i.e. 90 versus 180 g kg−1) increased the systolic blood pressure of their adult offspring (Langley & Jackson, 1994), as assessed by tail-cuff sphygmomanometry. To my knowledge, and surprisingly, no further study since has sought to corroborate these data with radiotelemetry and with some groups reporting similar increases in BP (Woods et al. 2001), no change (Martin et al. 2004) or reduced BP (after global nutrient restriction; Brennan et al. 2008), the field appears confusing, in part, because of the different methods used for measurement of BP. Does a maternal low protein diet lead to hypertensive offspring or alternatively, offspring more ‘stressed’ by the tail-cuff procedure (Tonkiss et al. 1998)? Rodford et al. (2008) in the current issue of The Journal of Physiology, revisit the MLP paradigm and report no change in tail-cuff measured systolic blood pressure in the offspring from 4 to 16 weeks of age, in contrast to much of the published literature. Rather, they observe marked effects on the structure and function of the endothelium that is, in part, sex specific. They interpret the data as an adaptation to the less than optimal prenatal environment that may mark ‘prehypertensives' (rats after all may live > 100 weeks). An optimal functioning endothelium is crucial to stable blood pressure control (e.g. through tonic generation of nitric-oxide and endothelins) and has one of the largest active surface areas of any organ in the body. The authors rightly argue that the lack of effect on resting (or stimulated) blood pressure measured by tail-cuff sphygmomanometry is perhaps not important; rather, demonstration of hypertension (relative to a contemporaneous control population) is a useful tool for demonstrating proof-of-principle (i.e. that the prenatal environment has delayed effects) but may not be symptomatic of clinical disease. Indeed, rats rarely, if ever, suffer cardiovascular disease. As the authors point out, in robust epidemiological studies the inverse relationship between low birth weight (an outcome often observed after MLP) and adult blood pressure is less clear cut than with clinical cardiovascular outcomes (Curhan et al. 1996). While the study of Rodford et al. focuses attention on the endothelium as a potentially important marker of prehypertension, many questions remain. How does MLP in utero affect endothelial remodelling? Is the adaptive response prenatal or postnatal (unresolved in the current study as the offspring were not cross-fostered)? Why the sex specificity? Fetal growth is supply driven; cut the supply (e.g. of nutrients) and growth slows, the available blood volume may redistribute to provide substrate for growth in essential organ beds (e.g. the brain and heart) leaving the peripheral cardiovascular network susceptible at a developmentally sensitive time (Berry, 1978; Folkow, 1993). In another 14 years perhaps these will be answered and the data can be translated into clinical practice.

HEMODYNAMIC EFFECTS OF CARVEDILOL IN PATIENTS WITH ARTERIAL HYPERTENSION

Aim. To evaluate the influence of carvedilol (Talliton, Egis, Hungary) on daily profile of blood pressure (BP), anatomical and functional conditions of left ventricle (LV) and cerebral circulation in patients with arterial hypertension (AH), stage II-III. Material and methods. 30 patients (10 men, 20 women, average age 51,9±7,9 y.o.) with AH II-III stage ( RSSC,2004) and with initially affected daily profile of BP, cerebral circulation, anatomical and functional disorders of LV took carvedilol 25-75 mg/d during 6 months. Hemodynamics was estimated by ambulatory BP monitoring, Doppler Echocardiography, and ultrasound Dopplerography of extra cranial vessels. Results. A normalizing effect of carvedilol on abnormal daily profile of BP and cerebral circulation was determined. The treatment resulted in the regress of LV hypertrophy with predominant reduction of interventricular septum thickness and also the transformation of concentrical LV hypertrophy in excentrical one. Conclusion. Long-term therapy with carvedilol in patients with AH II-III stage provides a stable BP control and cardioprotective effect, improves cerebral circulation.

Assessment of blood pressure during naproxen therapy in hypertensive patients treated with nicardipine

Nonsteroidal antiinflammatory drugs (NSAIDs) are known to attenuate the antihypertensive effects of a variety of antihypertensive agents including diuretics, beta-blockers, and vasodilators. Because of their unique mechanisms of actions, calcium channel blockers may not be subject to this interaction. This multicenter, double-blind, randomized, placebo-controlled study was designed to assess the effect of NSAID therapy on blood pressure control in stable hypertensive patients treated with a calcium channel blocker. One hundred patients with stable blood pressure control on 30 mg nicardipine three times a day were treated with 375 mg naproxen twice a day or placebo for 4 weeks. The mean diastolic blood pressures and estimated mean arterial pressures in both groups changed < 1 mm Hg during the 4 weeks of study drug treatment. None of the changes was significantly different from baseline and the two treatment groups were not significantly different from each other. Body weight in the placebo-treated patients did not change significantly whereas body weight in the naproxen-treated patients increased significantly, from 90.3 +/- 3.2 kg to 91.0 +/- 3.2 kg (mean = 0.7, P = .0003). At 4 weeks there was a mean loss of 0.1 kg in the placebo group and a mean gain of 0.4 kg in the naproxen group compared to baseline weights, neither of which was statistically significant (P = .60 and P = .071, respectively). These results indicate that despite a significant increase in body weight, the antihypertensive action of the calcium channel blocker nicardipine is not significantly affected by cotreatment with naproxen.

The hypotensive effect of nisoldipine: 24-hour blood pressure profile and serial alterations of renal and hormonal function

To investigate its hypotensive effect and mechanism of action, a long-acting calcium channel blocker, nisoldipine, was administered once daily for 12 days to eight subjects with essential hypertension. Daily changes in blood pressure and heart rate, as well as serial alterations in renal and hormonal function, were investigated. Nisoldipine significantly reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) on days 2 and 12 of treatment (daytime SBP: from 161.6 ± 4.0 mmHg to 141 ± 6.1 mmHg and 131.1 ± 4.7 mmHg, respectively; daytime DBP: from 100.4 ± 3.1 mmHg to 90.1 ± 4.8 mmHg and 81.8 ± 4.0 mmHg; nocturnal SBP: from 151.2 ± 3.6 mmHg to 132.0 ± 2.0 mmHg and 121.6 ± 1.6 mmHg; and nocturnal DBP: from 91.9 ± 1.0 mmHg to 81.3 ± 1.1 mmHg and 77.1 ± 1.1 mmHg). The extent of fluctuation of SBP and DBP, as indicated by the standard error of the mean (SEM) calculated from the blood pressures of each subject, was significantly increased on day 2. There was a moderate increase in heart rate on day 2 and it returned to the pretreatment level on day 12. Urinary sodium excretion was transiently increased on day 4, and body weight decreased significantly after administration of nisoldipine. Plasma renin activity and urinary norepinephrine level were increased significantly on day 6 and returned to baseline on day 12. These results suggest that once-daily administration of nisoldipine decreases blood pressure quite rapidly and that stable blood pressure control is obtained within 2 weeks. The antihypertensive mechanism of this drug may be partly related to a reduction of baroreceptor sensitivity and a reduction of total body water and sodium, as well as to its direct vasodilatory action.