Decrease In Ambulatory Blood Pressure Research Articles

Efficacy of Allisartan Isoproxil in the Treatment of Mild-to-Moderate Essential Hypertension.

Allisartan isoproxil is a selective nonpeptide angiotensin II (AT1) receptor blocker developed by China, this study aimed to assess its clinical efficacy for essential hypertension(EH). Patients with mild-to-moderate EH, selected at 44 sites in China from September 9, 2016, to December 7, 2018, were administered 240mg allisartan isoproxil daily for 4 weeks. Patients with controlled blood pressure(BP) continued monotherapy for 8 weeks, others were randomly assigned (1:1) to A + D group (allisartan isoproxil 240mg + indapamide 1.5mg) or A + C group (allisartan isoproxil + amlodipine besylate 5mg) for 8 weeks. BP were measured at week 4, 8 and 12. 2126 patients were included. After 12 weeks of treatment, systolic blood pressure(SBP) and diastolic blood pressure(DBP) decreased by 19.24 ±12.02 and 10.63 ±8.89 mmHg, respectively, and the overall BP control rate was 78.56%. The sitting blood pressures (SBP/DBP) decreased by 19.12 ±11.71/10.84 ±8.73 mmHg in patients with 12 weeks allisartan isoproxil monotherapy (both p < 0.0001). The BP reductions and control rates were comparable between A + D and A + C groups. 48 patients with monotherapy-controlled BP underwent ambulatory blood pressure monitoring, with a mean decrease in ambulatory blood pressure of 10.04 ±10.87/5.50 ±8.07 mmHg after 12 weeks of treatment, and consistent reductions between day and night. SBP and DBP had trough-to-peak ratios of 64.64% and 62.63% and smoothness indices of 3.82 and 2.92, respectively. An allisartan-isoproxil-based antihypertensive regimen can effectively control BP in patients with mild-to-moderate EH.

Effect of Adenotonsillectomy on Ambulatory Blood Pressure in Pediatric Obstructive Sleep Apnea: 6-Month Follow-up Study.

To investigate 24-hour ambulatory blood pressure changes 6 months after surgery among children with obstructive sleep apnea. Prospective interventional study. Tertiary medical hospital. Children aged 4 to 16 years with symptoms of obstructive sleep apnea (apnea-hypopnea index >1) were recruited. All children underwent adenotonsillectomy and postoperative polysomnography overnight. The 24-hour ambulatory blood pressure was measured before and 6 months after surgery. The study cohort enrolled 124 children: mean (SD) age, 7.3 (3.1) years; 73% boys. After surgery, the apnea-hypopnea index significantly decreased from 13.3 (18.1) to 3.3 (7.2) events per hour ( P < .001). Overall systolic blood pressure and diastolic blood pressure were not significantly different following surgery, while daytime systolic blood pressure was slightly increased (114.3 to 117.3 mm Hg, P < .01) postoperatively. The hypertensive group (n = 43) exhibited significantly decreased levels of overall diastolic, nighttime systolic, and nighttime diastolic blood pressure ( P < .05), and 54% of hypertensive children became nonhypertensive after surgery. The nonhypertensive group (n = 81) showed slightly increased levels of nocturnal overall systolic, daytime systolic, and nighttime systolic blood pressure. A generalized linear mixed model revealed that children with hypertension had a greater decrease in systolic and diastolic ambulatory blood pressure during the daytime and nighttime (all P < .05) than those without hypertension. Ambulatory blood pressure changes after adenotonsillectomy among children with obstructive sleep apnea are minimal. The decrease in ambulatory blood pressure after surgery is more prominent for hypertensive children than nonhypertensive children.

Effects of renal sympathetic denervation on cardiac sympathetic activity and function in patients with therapy resistant hypertension

BackgroundRenal sympathetic denervation (RSD) is currently being investigated in multiple studies of sympathetically driven cardiovascular diseases such as heart failure and arrhythmias. Our aim was to assess systemic and cardiac sympatholytic effects of RSD by the measurement of cardiac sympathetic activity and cardiovascular parameters. MethodsA total of 21 consecutive patients with refractory hypertension (daytime ambulatory blood pressure (BP) ≥150/100mmHg despite the use of 3 or more antihypertensive drugs), no evidence for secondary hypertension and normal renovascular anatomy were included. RSD was performed with the Medtronic Symplicity renal denervation catheter with an average of 4.2 (range 3–6) ablations per renal artery. To assess cardiac sympathetic activity, 123I-mIBG cardiac scintigraphy was performed before and 6weeks after. In addition, the effect of RSD on peripheral BP and cardiac hemodynamics were assessed non-invasively. Results123I-mIBG uptake before and after RSD was 1.7±0.4% vs. 1.7±0.5% at 15min. and 1.4±0.4% vs. 1.5±0.5% after 4h. As a consequence, washout rate was similar before (33.7±11.7%) and after RSD (30.1±12.6%, p=0.27). In line with earlier RSD studies, a significant drop in systolic office BP (−12.2mmHg, p=0.04) was detected, whereas the decrease in ambulatory BP was not significant. No changes were seen in heart rate, stroke volume or left ventricular contractility, both in supine position and after standing. ConclusionIn concert with previous reports, RSD leads to a significant drop in office BP. However, a reduction in sympathetic activity could not be demonstrated on a cardiac level.

Efficacy and Tolerability of Fixed-Dose Combination of Perindopril/Indapamide in Type 2 Diabetes Mellitus: PICASSO Trial

BackgroundHypertension and type 2 diabetes mellitus (T2DM) synergistically deteriorate the vascular environment, making blood pressure reduction challenging, and substantially increasing cardiovascular risk.MethodsIn the real-life, open-label, observational, PICASSO study, 9,257 hypertensive patients unsuccessfully treated with antihypertensives were switched to fixed-dose combination of perindopril 10 mg/indapamide 2.5 mg. In this subgroup analysis, we analyzed changes in blood pressure and laboratory parameters of 2,762 hypertensive patients with T2DM or pre-diabetes.ResultsAfter 3 months of treatment, significant decreases in office blood pressure were noted in the whole cohort (−27.0 ± 14.8/−12.7 ± 9.8 mmHg; p < 0.001). Significant decreases were also recorded in patients with grade 1 hypertension (19.2 ± 10.0/−9.4 ± 7.9 mmHg), grade 2 (29.2 ± 10.9/−13.3 ± 8.7 mmHg) and grade 3 (−45.1 ± 15.4/−21.5 ± 11.2 mmHg). Significant decreases in ambulatory blood pressure were also noted (n = 93). In patients previously treated with angiotensin-converting enzyme inhibitor ± hydrochlorothiazide or angiotensin receptor blocker ± hydrochlorothiazide, mean 24-h blood pressure decreased by 23.4 ± 13.9/11.5 ± 9.7 and 22.3 ± 8.7/10.4 ± 13.2 mmHg, respectively (p < 0.001). Treatment was well tolerated and the switch to treatment with perindopril/indapamide was associated with improvements in laboratory parameters.ConclusionsData from this diabetes subgroup analysis suggest that fixed combination of perindopril 10 mg/indapamide 2.5 mg should be routinely considered for the treatment of hypertension in diabetic patients who are unsuccessfully managed with other antihypertensive medications.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-014-0107-y) contains supplementary material, which is available to authorized users.

Randomized controlled trial of mindfulness-based stress reduction for prehypertension.

Mindfulness-based stress reduction (MBSR) is an increasingly popular practice demonstrated to alleviate stress and treat certain health conditions. MBSR may reduce elevated blood pressure (BP). Treatment guidelines recommend life-style modifications for BP in the prehypertensive range (systolic BP [SBP] 120-139 mm Hg or diastolic BP [DBP] 80-89 mm Hg), followed by antihypertensives if BP reaches hypertensive levels. MBSR has not been thoroughly evaluated as a treatment of prehypertension. A randomized clinical trial of MBSR for high BP was conducted to determine whether BP reductions associated with MBSR exceed those observed for an active control condition consisting of progressive muscle relaxation (PMR) training. Fifty-six men (43%) and women (57%) averaging (standard deviation) 50.3 (6.5) years of age (91% white) with unmedicated BP in the prehypertensive range were randomized to 8 weeks of MBSR or PMR delivered in a group format. Treatment sessions were administered by one treatment provider and lasted approximately 2.5 hours each week. Clinic BP was the primary outcome measure. Ambulatory BP was a secondary outcome measure. Analyses were based on intent to treat. Patients randomized to MBSR exhibited a 4.8-mm Hg reduction in clinic SBP, which was larger than the 0.7-mm Hg reduction observed for PMR (p = .016). Those randomized to MBSR exhibited a 1.9-mm Hg reduction in DBP compared with a 1.2-mm Hg increase for PMR (p = .008). MBSR did not result in larger decreases in ambulatory BP than in PMR. MBSR resulted in a reduction in clinic SBP and DBP compared with PMR. Trial Registration ClinicalTrials.gov identifier: NCT00440596.

Relationship Between Decrease in Ambulatory Blood Pressure and Heart Rate Variability Due to the Effects of Taking Olmesartan Medoxomil

BACKGROUNDS AND METHODS: A higher degree of clinical efficacy with olmesartan compared with other angiotensin receptor blockers, has been reported by several sources. In this study of 31 examples of cases of essential hypertension, Holter electrocardiogram, ambulatory blood pressure monitoring and pulse wave velocity (PWV) measurements were performed before and after substituting olmesartan 20 mg for candesartan 8 mg antihypertensive drug therapy. Following the therapeutic change, daily average systolic and diastolic blood pressures were decreased by 6.7 +/- 9.3 mmHg and 3.6 +/- 8.3 mmHg, respectively, with olmesartan 20 mg; PWV was also significantly decreased. Holter electrocardiogram heart rate variability spectral analysis demonstrated that none of the very low frequency (VLF), high frequency (HF) and low frequency (LF)/HF components were significantly altered. However, a significant correlation was observed between the LF/HF component and blood pressure difference, when blood pressure and heart rate variability components in each individual case were studied. This study shows that olmesartan has a stronger antihypertensive effect in comparison to candesartan, and does not generate reflex sympathoexcitatory activity.

Acute Aerobic Exercise Reduces 24-H Ambulatory Blood Pressure Levels in Long-Term-Treated Hypertensive Patients

BACKGROUNDEven with anti-hypertensive therapy, it is difficult to maintain optimal systemic blood pressure values in hypertensive patients. Exercise may reduce blood pressure in untreated hypertensive, but its effect when combined with long-term anti-hypertensive therapy remains unclear. Our purpose was to evaluate the acute effects of a single session of aerobic exercise on the blood pressure of long-term-treated hypertensive patients.METHODSFifty treated hypertensive patients (18/32 male/female; 46.5±8.2 years; Body mass index: 27.8±4.7 kg/m2) were monitored for 24 h with respect to ambulatory (A) blood pressure after an aerobic exercise session (post-exercise) and a control period (control) in random order. Aerobic exercise consisted of 40 minutes on a cycle-ergometer, with the mean exercise intensity at 60% of the patient’s reserve heart rate.RESULTSPost-exercise ambulatory blood pressure was reduced for 24 h systolic (126±8.6 vs. 123.1±8.7 mmHg, p=0.004) and diastolic blood pressure (81.9±8 vs. 79.8±8.5 mmHg, p=0.004), daytime diastolic blood pressure (85.5±8.5 vs. 83.9±8.8 mmHg, p=0.04), and nighttime S (116.8±9.9 vs. 112.5±9.2 mmHg, p<0.001) and diastolic blood pressure (73.5±8.8 vs. 70.1±8.4 mmHg, p<0.001). Post-exercise daytime systolic blood pressure also tended to be reduced (129.8±9.3 vs. 127.8±9.4 mmHg, p=0.06). These post-exercise decreases in ambulatory blood pressure increased the percentage of patients displaying normal 24h systolic blood pressure (58% vs. 76%, p=0.007), daytime systolic blood pressure (68% vs. 82%, p=0.02), and nighttime diastolic blood pressure (56% vs. 72%, p=0.02). Nighttime systolic blood pressure also tended to increase (58% vs. 80%, p=0.058).CONCLUSIONA single bout of aerobic exercise reduced 24h ambulatory blood pressure levels in long-term-treated hypertensive patients and increased the percentage of patients reaching normal ambulatory blood pressure values. These effects suggest that aerobic exercise may have a potential role in blood pressure management of long-term-treated hypertensive.

Expedited blood pressure control with initial angiotensin II antagonist/diuretic therapy compared with stepped-care therapy in patients with ambulatory systolic hypertension

The present study investigated whether initiating therapy with a combination of losartan (L) and hydrochlorothiazide (HCTZ) allows for faster blood pressure (BP) control and fewer medications than the usual stepped-care approach in patients with stage 2 or 3 hypertension and ambulatory systolic hypertension. Patients with a mean daytime systolic ambulatory BP (ABP) of 135 mmHg or higher were randomly assigned to receive L 50 mg plus HCTZ 12.5 mg titrated to L 100 mg plus HCTZ 25 mg versus HCTZ 12.5 mg plus atenolol 50 mg. Amlodipine 5 mg was then added, if needed, to achieve a BP goal of less than 130 mmHg. Treatment titration was based on ABP. Significantly more patients randomly assigned to L/HCTZ (63.5%) than stepped-care (37.5%; P=0.008) achieved the primary end point (daytime systolic BP of less than 130 mmHg). Initial L/HCTZ induced significantly greater decreases in ABP during each 24 h period after six weeks of therapy. Although reductions in systolic and diastolic ABP were not statistically different at the end of the study, ABP reduction was significantly greater (P<0.001) with the L/HCTZ-based regimen. Twice as many patients in the L/HCTZ group achieved the goal ABP with no more than two drugs (30.0% versus 14.7%; P=0.03). Moreover, tolerability was significantly better (P=0.006) in the L/HCTZ group, with a 40.0% incidence of adverse events, versus 65.6% in the stepped-care group. Initiating antihypertensive therapy with the combination of L/HCTZ in patients with stage 2 or 3 hypertension and ambulatory systolic hypertension reaches a target BP faster in a higher proportion of patients, with fewer adverse events and less need for a third drug regimen than the conventional stepped-care approach.

Effects of Valsartan or Amlodipine Alone or in Combination on Plasma Catecholamine Levels at Rest and During Standing in Hypertensive Patients

To compare the effects of valsartan and amlodipine alone or in combination on plasma norepinephrine (NE) at rest and standing for 10 minutes in patients with hypertension, 47 patients with a sitting diastolic blood pressure (BP) (DBP)>95 mm Hg and<110 mm Hg were randomized in a double-blind fashion to either valsartan or amlodipine. During the first 4 weeks of treatment, patients received a low dose of either valsartan (80 mg) or amlodipine (5 mg). The patients were force-titrated to the high dose of either drug (160 or 10 mg) for 4 weeks. After 8 weeks of therapy, those who still had a DBP>90 mm Hg (nonresponders) received combination therapy with the other drug, whereas patients with a DBP<90 mm Hg (responders) continued on monotherapy. Decreases in ambulatory BP and clinic systolic BP and DBP were significant (P<.05) after 8 weeks' therapy with no difference between the 2 groups. Amlodipine but not valsartan as monotherapy consistently increased NE levels at rest and enhanced NE levels during standing. Valsartan decreased basal NE in responders. Combination therapy with valsartan and amlodipine did not attenuate the rise in NE levels induced by amlodipine. This study indicates that therapy with amlodipine increases peripheral sympathetic basal tone and reactivity to standing in patients with hypertension, whereas valsartan does not. Combined therapy with amlodipine/valsartan did not attenuate the sympathetic activation induced by amlodipine. The hypotensive action of valsartan may be mediated in part by an inhibition of the sympathetic baroreflex in patients with hypertension.

Functional variants of the angiotensinogen gene determine antihypertensive responses to angiotensin-converting enzyme inhibitors in subjects of African origin

To determine whether the response to angiotensin-converting enzyme inhibitor (ACEI) monotherapy in subjects of African origin is determined by genetic variants within the angiotensinogen (AGT) gene. A total of 194 hypertensive patients of African ancestry were recruited from district clinics in Johannesburg, South Africa. Eighty patients received open-label ACEI (enalapril or lisinopril) monotherapy, and 114 open-label calcium antagonist (nifedipine) as a drug class comparator. Twenty-four hour ambulatory blood pressure (ABP) monitoring was performed at baseline (off medication) and after 2 months of therapy. DNA was analysed for functional variants (-217G-->A and -20A-->C) of the AGT gene. The impact of genotype on ABP responses to ACEI monotherapy or calcium antagonists; and on plasma aldosterone and renin levels after ACEI monotherapy was assessed. Adjusting for baseline ABP and type of ACEI in the ACEI-treated group, the -217G-->A variant predicted ABP responses to ACEI (n = 77; P < 0.01), but not to nifedipine (n = 108). ACEI in patients with the AA genotype of the -217G-->A variant failed to elicit an antihypertensive response [change in ABP, mmHg: systolic blood pressure (SBP) +0.84 +/- 2.89, P = 0.78; diastolic blood pressure (DBP) -0.47 +/- 1.74, P = 0.79]. In contrast, those patients with at least one copy of the -217G allele developed a 7.23 +/- 1.55 and 5.38 +/- 1.12 mmHg decrease (P < 0.0001) in SBP and DBP, respectively, after ACEI administration. Similarly, the -20A-->C variant predicted ABP responses to ACEI monotherapy (P < 0.01) but not to nifedipine. Moreover, patients who were AA genotype for both variants failed to develop an antihypertensive response to ACEI (change in ABP, mmHg: SBP +1.06 +/- 3.05, P = 0.73; DBP -0.39 +/- 1.83, P = 0.83); whereas patients with at least one copy of both the -217G and the -20C allele developed substantial decreases in ABP (change in ABP, mmHg: SBP -14.08 +/- 3.72, P < 0.0001; DBP -9.62 +/- 2.74, P < 0.0001). Patients with at least one copy of the -217G allele demonstrated a significant reduction in the aldosterone-to-renin ratio (-0.098 +/- 0.035, P < 0.01), whereas in those patients who were -217AA genotype the ratio was unchanged (-0.03 +/- 0.16, P = 0.85). Functional variants of the AGT gene contribute to the variability of antihypertensive responses to ACEI monotherapy in individuals of African ancestry, with genotype determining whether or not responses occur.

Ramipril in the treatment of hypertension and proteinuria in children with chronic kidney diseases

Background Angiotensin-converting enzyme inhibitors are the drugs of choice in renal hypertension. The efficacy and safety of ramipril in adults has been proved; however, data on effectiveness of ramipril in children are few. The aim of the present study was to investigate the effect of ramipril on blood pressure (BP) and proteinuria in children with chronic kidney diseases. Methods A total of 31 children (median age 11.3 years, range 1.9–19.8 years) with various chronic nephropathies and hypertension or proteinuria were prospectively treated with ramipril for 6 months. Blood pressure was evaluated using ambulatory BP monitoring and hypertension was defined as mean BP equal to or greater than the 95th percentile for healthy children. Proteinuria was defined as protein excretion ≥100 mg/m 2/24 h. The starting dose of ramipril was 1.5 mg/m 2/24 h once daily. In 27 children it was given as monotherapy. Results The median decrease in ambulatory BP was 11 mm Hg for daytime systolic, 10 mm Hg for daytime and nighttime diastolic, and 8 mm Hg for nighttime systolic BP. Hypertension normalized in 55% of the children. Proteinuria decreased in 84% of the children with pathologic proteinuria; the median decrease was 51%. A positive correlation was found between initial proteinuria and change of proteinuria ( r = 0.95, P < .001). Glomerular filtration rate and serum potassium level did not change significantly. One child developed a cough that was believed to be related to ramipril. Conclusions Ramipril is an effective and safe drug in children with chronic kidney diseases associated with hypertension, proteinuria, or both.

Comparison of the effects of losartan and angiotensin converting enzyme inhibitor on nocturnal blood pressure in patients with stroke

Background: Therapy of nocturnal hypertension was shown to be beneficial for primary and secondary prevention of stroke. We investigated the effects of angiotensin II antagonist (losartan) and angiotensin converting enzyme (ACE) inhibitor (quinapril) on nocturnal blood pressure and sympathetic nervous activity in patients with hypertension and stroke. Methods: According to a prospective, randomized, crossover design, 30 hypertensive patients with a previous history of stroke were assigned randomly to receive losartan (50 mg) or quinapril (10 mg) once daily for 4 weeks. The patients were switched to the alternative regime for an additional 4-week period. In the last week of each treatment, 24-h ambulatory blood pressure (BP) monitoring was performed every 30 min, and 24-h urine was collected for the measurement of catecholamine. Results: Neither systolic nor diastolic BPs during daytime differed between losartan and quinapril treatments, but those during nighttime were lower under losartan treatment than under quinapril treatment. The nocturnal decreases in systolic and diastolic BPs were both greater under losartan treatment than under quinapril treatment. The nocturnal decrease in urinary norepinephrine (NE) excretion was greater under losartan treatment than under quinapril treatment. Conclusions: Losartan augments the nocturnal decrease in ambulatory BP compared with that of quinapril in patients with a previous history of stroke, presumably via the suppression of nocturnal sympathetic nervous activity.

Weight loss and weight maintenance, ambulatory blood pressure and cardiac autonomic tone in obese persons with the metabolic syndrome.

Cardiac autonomic function may play a role in obesity-associated hypertension. Most studies on the effects of weight loss on blood pressure and autonomic function do not distinguish between acute or continuing weight loss and steady-state weight maintenance after weight loss. We sought to clarify the changes in ambulatory blood pressure, heart rate and heart rate variability as assessed by spectral analysis during rapid weight loss and extended weight maintenance. Abdominally obese (body mass index 35.2 +/- 2.1 kg/m2, waist 114.3 +/- 9.0 cm) men and women (n = 41) with the metabolic syndrome. The 34 men and women completing the 1-year weight maintenance period lost 14.6 +/- 3.5 kg during the 9-week very-low-calorie diet and maintained a 12.5 +/- 7.5 kg weight loss to the end of the trial. Ambulatory 24-h blood pressure decreased dramatically during the diet (-9.0 +/- 8.0/-4.6 +/- 4.9 mmHg), but had risen to near baseline levels by the end of weight maintenance (-2.2 +/- 8.2 /-1.2 +/- 6.1 mmHg). Night-time heart rate decreased (-5.5 +/- 9.6 beats/min, P = 0.012), and heart rate variability total and low-frequency power measured during 5 min of controlled breathing increased by 46-56% (P = 0.003-0.09) during rapid weight loss. These changes gradually attenuated during weight maintenance, and only the change in night-time heart rate was still of borderline significance after 1 year of weight maintenance (-3.6 +/- 8.6 beats/min, P = 0.063). Heart rate variability high-frequency power tended to increase during weight loss and weight maintenance. Despite successful weight maintenance, the decrease in ambulatory blood pressure after rapid weight loss was largely transient. The increase in parasympathetic tone was more sustained, but also gradually attenuated during 1 year of weight maintenance.

Effect of losartan on nocturnal blood pressure in patients with stroke: comparison with angiotensin converting enzyme inhibitor

Background Treatment of nocturnal hypertension has been reported to be beneficial for primary and secondary prevention of stroke. We compared the effects of angiotensin II antagonist (losartan) and angiotensin converting enzyme inhibitor (quinapril) on nocturnal blood pressure (BP) and sympathetic nervous activity in patients with hypertension and stroke. Methods According to a prospective, randomized, cross-over design, 30 hypertensive patients with a previous history of stroke (25 hemorrhage, 5 infarction) were assigned randomly to receive losartan (50 mg) or quinapril (10 mg) once daily for 4 weeks. The patients were switched to the alternative regimen for an additional 4-week period. In the last week of each treatment, 24-h ambulatory BP monitoring was performed every 30 min, and 24-h urine was collected for the measurement of catecholamine. Results Neither systolic nor diastolic BP during daytime differed between losartan and quinapril treatments, but those during nighttime were lower with losartan treatment than with quinapril treatment. The nocturnal decreases in systolic and diastolic BP were both greater with losartan treatment than with quinapril treatment (systolic BP: 6.1% ± 5.9% v 2.5% ± 6.9%, diastolic BP: 6.4% ± 6.5% v 3.3% ± 7.8%, both P < .05). The nocturnal decrease in urinary norepinephrine excretion was greater with losartan treatment than with quinapril treatment (52.8% ± 9.7% v 42.8% ± 17.2%, P < .05). Conclusions Losartan enhances the nocturnal decrease in ambulatory BP compared with that of quinapril in patients with a previous history of stroke presumably by way of the suppression of nocturnal sympathetic nervous activity.

Transdermal Estrogen Replacement Therapy Decreases Sympathetic Activity in Postmenopausal Women

Menopause heralds a dramatic increase in incident hypertension, suggesting a protective effect of estrogen on blood pressure (BP). In female rats, estrogen has been shown to decrease sympathetic nerve discharge (SND) and BP. SND, however, has not been recorded during estrogen replacement therapy (ERT) in humans. Methods and Results-In 12 normotensive postmenopausal women, we conducted a randomized crossover placebo-controlled study to test whether chronic ERT caused a sustained decrease in SND and BP. Twenty-four-hour ambulatory BP, SND, and arterial baroreflex sensitivity were measured before and after 8 weeks of transdermal estradiol (200 microgram/d), oral conjugated estrogens (0.625 mg/d), or placebo. To test the acute effects of estrogen on SND, additional studies were performed in the same women receiving intravenous conjugated estrogens or sublingual estradiol. After 8 weeks of transdermal ERT, the basal rate of SND decreased by 30% (from 40+/-4 to 27+/-4 bursts per minute, P=0.0001) and ambulatory diastolic BP fell by 5+/-2 mm Hg (P=0.0003). In contrast, SND and BP were unaffected either by 8 weeks of oral ERT or by acute estrogen administration. Neither transdermal nor oral ERT had any effects on baroreflex sensitivity. In normotensive postmenopausal women, chronic transdermal ERT decreases SND without augmenting arterial baroreflexes and causes a small but statistically significant decrease in ambulatory BP. Sympathetic inhibition is evident only with chronic rather than acute estrogen administration, implying a genomic mechanism of action. Because the effects of transdermal ERT are larger than those of oral ERT, the route of administration may be an important consideration in optimizing the beneficial effects of ERT on BP and overall cardiovascular health.

Vagal Cardiac Activity in Essential Hypertension: The Effects of Metoprolol and Ramipril

Cardiovascular parasympathetic activity is attenuated in essential hypertension. Both β-adrenoceptor antagonists and angiotensin converting enzyme inhibitors have been reported to increase vagal modulation of heart rate and baroreflex sensitivity, but the relations between the antihypertensive and vagal cardiac effects of these drugs have remained unclear in essential hypertension. In the present study we evaluated the effects of a 4-week crossover monotherapy with metoprolol and ramipril on spectrum analysis indices of heart rate variability in the supine rest and head-up tilted positions, baroreflex sensitivity (phenylephrine method), and 24-h ambulatory blood pressure (BP) in 12 formerly untreated stage 1–2 essential hypertensive patients. Compared to the pretreatment values, both drugs decreased BP similarly and significantly. However, the drugs showed different effects on cardiac vagal activity: metoprolol increased significantly mean R-R interval, R-R interval total, and high-frequency variability at supine rest and baroreflex sensitivity, but ramipril did not significantly affect these variables. The metoprolol-induced decrease in ambulatory BP correlated with the prolongation of the R-R interval and the increase of high-frequency variability at supine rest. The present data show that 4-week treatment with metoprolol increases tonic and reflex vagal cardiac activity, whereas ramipril does not affect vagal cardiac control in essential hypertension. Increase in vagal activity may contribute to the BP-lowering effect of metoprolol in hypertensive patients.

Ambulatory blood pressure monitoring in patients with essential hypertension treated with a new calcium antagonist, cilnidipine.

Cilnidipine (FRC-8653), a new dihydropyridine calcium antagonist, was given to 14 hospitalized patients with essential hypertension, and 24-hour ambulatory blood pressure (BP) monitoring was performed. Once-daily administration of cilnidipine (5-20 mg) for 1-3 weeks decreased the 24-hour average BP significantly from 149 +/- 4/88 +/- 2 mmHg to 141 +/- 3/82 +/- 2 mmHg without any change in the pulse rate. The decrease in ambulatory BP by cilnidipine was evident during the daytime (156 +/- 4/93 +/- 2 mmHg to 143 +/- 5/84 +/- 2 mmHg, p < 0.01 for systolic BP and p < 0.01 for diastolic BP), while it was mild during nighttime (141 +/- 4/80 +/- 2 mmHg to 133 +/- 4/76 +/- 3 mmHg, p < 0.05 for systolic and ns for diastolic BP). The decrease in the ambulatory BP over the whole day and during the nighttime was significantly correlated with the basal ambulatory BP levels. When the subjects were divided into the high ambulatory BP (n = 7) and low ambulatory BP (n = 7) groups, the BP reduction by cilnidipine was evident throughout 24 hours in the high ambulatory BP group, while it was mild and significant only during daytime in the low ambulatory BP group. In summary, once-daily cilnidipine exerts a sufficient and prolonged reduction of BP without an increase in the pulse rate in patients with hypertension. The potency of cilnidipine to decrease ambulatory BP may depend on the basal ambulatory BP level. Cilnidipine is thus a useful antihypertensive drug that may not cause an excessive decrease in BP or a reflex tachycardia.