Reduce Blood Pressure Variability Research Articles

Visit-to-visit blood pressure variability and risk for progression of cardiovascular and renal diseases

Recent data have highlighted the shortcomings of the usual blood pressure hypothesis in posthoc analyses of randomized controlled trials led in populations at high cardiovascular risk and have emphasized the importance of an increased visit-to-visit variability of blood pressure in predicting cardiovascular events. Over the last 2 years, the prognostic value of visit-to-visit blood pressure variability has been substantially confirmed in a wide spectrum of clinical populations, in studies investigating both cardiovascular outcomes and target organ damage. There is an obvious need to design studies to prospectively determine the causes of increased visit-to-visit blood pressure variability, its best estimate and whether or not treatments that reduce blood pressure variability (and to what extent/target) improve clinical outcome.

Association of Age and BP Variability with Long-term Mortality in Hemodialysis Patients

Background/Aims: Blood pressure (BP) variability is known as a poor prognostic factor for cardiovascular outcomes. This study assessed the prognostic significance of BP variability in association with increasing age in hemodialysis patients. Methods: We retrospectively analyzed 2,174 patients on hemodialysis from March 2005 to December 2012. The impact of intradialytic and interdialytic BP variability on all-cause mortality according to age groups was analyzed. Results: Kaplan-Meier survival curves for 5-year cumulative mortality showed higher mortality in patients with higher intradialytic systolic and diastolic BP variability as well as interdialytic systolic and diastolic BP variability (log-rank p=0.006, <0.001, 0.018 and < 0.001) in patients aged <55 years, but not in older age groups. Cox proportional analysis revealed that 5-year mortality was associated with intradialytic diastolic BP variability in patients aged <55 years (HR, 2.03 CI, 1.24-3.32). Conclusion: The overall mortality was associated with BP variability in patients aged <55 years, but not in older ages. This result suggests that younger hemodialysis patients with BP variability require further medical attention and intervention to reduce BP variability.

A Recipe for Reducing Blood Pressure Variability: Adding Blood Flow to the Mix

To the Editor: An important medical advancement during the last 3 decades has been the development of accurate but noninvasive blood pressure monitoring devices. The successful application of such technology has lead to growing recognition that identifying elevated blood pressure variability (BPV) across a wide range of time scales may be useful in predicting poorer health outcomes. Thus, with great interest we read the article by Matsui et al1 showing that day-by-day BPV was lower in patients treated with an angiotensin II receptor blocker/calcium channel blocker combination compared with those treated with an angiotensin II receptor blocker/diuretic combination. This study raises the exciting possibility of potential methods for treating elevated BPV. In light of treatment possibilities, …

Response to A Recipe for Reducing Blood Pressure Variability: Adding Blood Flow to the Mix

We thank Tzeng et al1 for their interest in our recent findings2 and for showing their valuable data. The main finding of this study is that the addition of a long-acting dihydropyridine calcium channel blocker (CCB; azelnidipine) to an angiotensin II receptor blocker led to a significantly larger reduction in day-by-day home blood pressure (BP) variability (midterm BPV) than the addition of a thiazide diuretic (hydrochlorothiazide), despite similar reductions in mean home BP in both groups.2 It would be of great interest to examine the impact of BPV on the variability of regional blood flow …

Calcium Antagonist Added to Angiotensin Receptor Blocker: A Recipe for Reducing Blood Pressure Variability?

See related article, pp 1132–1138 The results of a number of studies performed over the years support the hypothesis that short-term blood pressure (BP) variability (BPV) assessed within 24 hours is an independent determinant of organ damage and cardiovascular events in hypertension.1,2 More recently, a few articles have raised interest also in BP fluctuations occurring over longer time periods. Rothwell et al3 assessed the variability in clinic BP or in average 24-hour ambulatory BP values occurring between visits. They analyzed previously collected data demonstrating an independent association of such visit-to-visit variability with (mainly) cerebrovascular events. The principal disadvantage of this approach, however, is its limited applicability in the daily management of hypertensive patients, where it is difficult to obtain BP data under a stable antihypertensive treatment regimen over a consistent number of visits. An alternative method, devoid of this difficulty, is to assess day-by-day BPV making use of home BP values obtained over several days. Its validity is supported by studies demonstrating the relationship of day-by-day BPV with cardiovascular outcomes.4 However, in spite of the data supporting the clinical relevance of BP fluctuations over time, a number of reasons have until now prevented the introduction of BPV assessment in daily clinical management of hypertension. Among them is the yet missing direct evidence in humans that a reduction in BPV by treatment provides cardiovascular protection beyond that offered by BP lowering. Moreover, although animal studies suggested the possible beneficial role of calcium channel blockers (CCBs) in lowering BPV independent of mean BP reduction,5 longitudinal data in humans on the ability of antihypertensive drugs to reduce BPV independently from their effect on mean BP levels are still largely missing. A …

The Role of Clinical Decision Support Tools to Reduce Blood Pressure Variability in Critically Ill Patients Receiving Vasopressor Support

Current monitoring systems for patients receiving vasopressor support generally rely on bedside monitors with audible alarms that are activated when blood pressure declines below pre-established thresholds, which can result in fluctuations that may increase risk of myocardial ischemia. This pilot study evaluated the effects of three bedside monitors on mean arterial blood pressure and percentage of time at mean arterial pressure among critically ill patients. The monitors were the standard display with audible alarm or one of two types of clinical decision support systems including Intellivue Horizon Trends (Philips Healthcare, Andover, MA) and Horizon Trends and ST Map (Philips Healthcare). Patients in the two groups monitored with Horizon Trends had significantly higher mean arterial pressure (72.8 ± 7.0 mm Hg) compared with those monitored with the standard monitor (68.1 ± 6.8 mm Hg; P= .004). Patients monitored with Horizon Trends also spent a significantly higher percentage of time within their target mean arterial pressure range compared with those in the standard monitor group (P = .031). These findings suggest that further study is needed to assess the impact of clinical decision support tools on management of blood pressure variability in critically ill patients receiving vasopressor therapy.

Blood Pressure Variability and Its Management in Hypertensive Patients

Optimizing treatment for hypertension has focused on reducing cardiovascular risk through reduction of mean blood pressure (BP) under the basic assumption that lower is better, as long as diastolic BP is sufficient to maintain coronary perfusion. However, antihypertensive therapy as currently practiced does not eliminate all hazards associated with BP elevation. Blood pressure variability (BPV) correlates closely with target-organ damage independent of mean BP and transient increases in BP are also triggers of vascular events. So far, there is no definitive outcome data relating specific reduction in BPV to decline cardiovascular events or death. Thus, the decision whether BPV should be considered a new therapeutic target is left to the clinical judgment of physicians and individualized for each patient. However, new evidence suggests that taking an antihypertensive medication at bedtime significantly affects BPV and lowers the risk of cardiovascular events and death. This strategy may provide a means of individualizing treatment of hypertension according to the circadian BPV of each patient and may be a new option to optimize BP control and reduce risk.

Clinical observation on Songlingxuemaikang combined with losartan in treatment of female menopausal bypertension

Objective To explore the effect of Songlingxuemaikang combined with losartan on the blood pressure and quality of life in female patients with menopausal hypertension.Methods 87 female patients with menopausal hypertension were randomly divided into combined group (Songlingxuemaikang combined with losartan group,44 cases) and the control group(losartan alone,43 cases).Before and after treatment the ambulatory blood pressure (ABMP) was monitored for 24h,and blood lipids and clinical symptoms were observed.Results After two months treatment,the blood pressure variability and nighttime blood pressure decrease rate of the combination group significantly reduced,and better than those of the control group( all P ＜0.05) ;The effective rate and efficiency rate of the combination group were 90.9％,63.6％ respectively,and was higher than 74.4％,39.5％ in the control group( x2 =4.15,5.06,all P ＜ 0.05 ).The clinical symptoms improving,total cholesterol ( TC ) reducing,density lipoprotein (LDL-C) lowing in the combination group was superior to the control group( all P ＜ 0.05).Conclusion Songlingxuemaikang combined with losartan in treatment of female patients with menopausal hypertension had a good antihypertensive effect,and could reduce blood pressure variability in menopausal women,improve the symptoms of menopause and lipid metabolism,incresse the quality of lfie of patients with menopausal hypertensive. Key words: Menopausal syndrome; Hypertension; Female; Songlingxuemaikang; Losartan

Blood pressure variability and arterial stiffness

Blood pressure variability (BPV) is defined by the standard deviation of a given sample of population of normotensive or hypertensive subjects. Recent studies have suggested that this parameter might constitute a cardiovascular risk factor. Reduction of blood pressure variability could be an important purpose of anti-hypertensive treatment, as suggested from experimental studies. In a double-blind controlled investigation, the thiazide compound indapamide was compared to placebo, to the angiotensin blocker candesartan and to the calcium-entry blocker amlodipine for 12 weeks treatment. The 3 drugs reduced significantly and identically blood pressure. Only indapamide and amlodipine reduced significantly BPV. This study was the first to demonstrate the interest of BPV in the setting of a double-blind, placebo controlled, trial.

Synergism of irbesartan and amlodipine on hemodynamic amelioration and organ protection in spontaneously hypertensive rats

To investigate the synergism of low-doses of amlodipine and irbesartan on reduction of blood pressure variability (BPV), amelioration of baroreflex sensitivity (BRS) and organ protection in spontaneously hypertensive rats (SHR). The rats were administered amlodipine (1 mg·kg(-1)·d(-1)) alone, irbesartan (10 mg·kg(-1)·d(-1)) alone, or the combination of the two drugs for 4 months. The drugs were mixed into the rat chow. Blood pressure (BP) was continuously monitored in conscious animals. After the determination of BRS, the rats were killed for morphological evaluation of organ damages. The combination of low-dose irbesartan and amlodipine had statistically significant synergism on reduction of BP and BPV, amelioration of BRS and organ protection in SHR. Multiple regression analysis showed that the decrease in left ventricular hypertrophy was associated with the decrease in systolic BPV (r=0.665, P<0.01); the decrease in aortic hypertrophy was associated with the increase in BRS (r=0.656, P<0.01); and the amelioration in renal lesion was associated with the increase in BRS (r=0.763, P<0.01) and the decrease in systolic BPV (r=0.706, P<0.01). Long-term treatment with a combination of low-doses of amlodipine and irbesartan showed significant synergism on reduction of BP and BPV, restoration of BRS and organ protection in SHR. Besides BP reduction, the enhancement of BRS and reduction of BPV might contribute to the organ protection.

Effect of Antihypertensive Agents on Blood Pressure Variability

To investigate the effect of different antihypertensive agents on blood pressure (BP) variability (BPV) and the underlying mechanism, we analyzed the ambulatory BP monitoring data of 577 patients before and after 3-month antihypertensive treatment, in the Natrilix SR Versus Candesartan and Amlodipine in the Reduction of Systolic Blood Pressure in Hypertensive Patients (X-CELLENT) Study, a multicenter, multinational, randomized, double-blind, placebo-controlled study with 4 parallel treatment arms (placebo, candesartan, indapamide sustained release, and amlodipine). Within-subject mean and SD of 24-hour BP, weighted by time interval between consecutive readings, were calculated in 3 time frames (daytime, nighttime, and 24 hours) to evaluate BP and BPV. The mean 24-hour heart rate (HR) and HR variability were calculated with the same algorithms. We found that the 3 antihypertensive drugs had a similar BP-lowering effect (P<0.001 for all), but amlodipine (P<0.007) and indapamide sustained release (P<0.04) were the only agents associated with a significantly decreased BPV after 3-month treatment. On the other hand, the major determinants of BPV at baseline were age, mean BP, and the corresponding HR variability. However, the reduction in BPV by amlodipine was significantly associated with the reduction in BP (P<0.006) and the reduction in HR variability (P<0.02), whereas the corresponding reduction by indapamide sustained release was only associated with the reduction in HR variability at night (P=0.004). In summary, 3-month amlodipine or indapamide sustained release treatment was associated with a significant reduction in BPV, and the mechanism of those reductions was possibly attributable to lowering BP or ameliorating the autonomic nervous system regulation or both. The combination of the 2 agents might help to optimize such properties.

Rate of blood pressure changes assessed by 24 h ambulatory blood pressure monitoring: another meaningful index of blood pressure variability?

Data collected over the past 60 years, thanks to the introduction of ambulatory blood pressure monitoring (ABPM) techniques, have clearly shown that blood pressure (BP) is a highly variable parameter [1]. Such a solid awareness, however, has not found a suitable translation into clinical practice yet, and the evaluation of BP-related cardiovascular risk is still largely confined, in the best case, to the assessment of average BP values from a series of measurements (obtained by ambulatory or home BPM), while most recommendations related to hypertension management are still based on isolated clinic measurements [2,3]. This despite the availability of growing evidence that BP variability is an independent predictor of organ damage and cardiovascular events [4– 9]. A few reasons may explain the difficulties in introducing BP variability as a routine clinical tool. One, the complex nature of the mechanisms underlying an increase in BP excursions makes the clinical interpretation and practical use of estimates of BP variability difficult. Indeed, an increased amplitude and frequency of BP fluctuations may reflect alterations of different factors involved in cardiovascular control such as impairment of autonomic or hormonal regulation, renal dysfunction, and increased arterial stiffness [10]. Two, the lack of solid evidence supporting the efficacy of any specific treatment in reducing BP variability is associated with the even more important lack of evidence, except for a few animal studies [11], that its reduction may be actually beneficial in reducing cardiovascular risk. Three, the fact that simple conventional estimates of BP variability based on the calculation of 24 h, daytime or night-time standard deviation (SD) of either systolic or diastolic average BP, even if independently related to outcome, appear to have a rather limited predictive power compared to other more traditional risk factors [4–7,12]. Four, the awareness that the SD of BP average values, com-

Perindopril for the treatment of hypertension

Introduction:Treatment of hypertension is fundamental for the prevention of cardiovascular events and mortality. This review focuses on the specific benefits of the ACE inhibitor perindopril.Areas covered:A systematic literature search is undertaken for supporting the pharmacological proprieties and clinical efficacy of perindopril in the treatment of hypertension. Good tissue penetration, strong affinity for ACE and a long duration of action support the dose-dependent blood pressure lowering efficacy. Perindopril in combination with amlodipine significantly reduced total and cardiovascular mortality as compared to atenolol/diuretic in large-scale clinical trials of hypertensive patients. A greater reduction in blood pressure variability, central blood pressure and specific vascular protective proprieties of perindopril (improvement in arterial stiffness and endothelial function) might explain these results. Cardiovascular prevention with perindopril, in combination with indapamide, has been also shown in the elderly and patients with diabetes, cardio- and cerebrovascular diseases.Expert opinion:Perindopril is effective and safe for blood pressure control with a dose-dependent effect. Combination therapy with indapamide or amlodipine reduces cardiovascular events and mortality in hypertensive patients. Pharmacological proprieties and results of clinical trials support the choice of perindopril as an appropriate treatment for hypertensive patients.

Synergism of Telmisartan and Amlodipine on Blood Pressure Reduction and Cardiorenal Protection in Hypertensive Rats

This study was designed to investigate the effects of telmisartan and amlodipine on reduction of blood pressure (BP), myocardial hypertrophy, and renal injury in hypertensive rats. In acute experiments, the BP was measured in conscious freely moving rats. Spontaneously hypertensive rats were treated with intragastric administration of amlodipine (1, 2, 4 mg/kg), telmisartan (4, 8, 12, 16, 20 mg/kg), and their different combinations (4 + 4, 2 + 4, 4 + 8, 4 + 12, 1 + 4, 2 + 8, 4 + 16, 2 + 12, 1 + 8, 2 + 16, 2 + 20, 1 + 12, 1 + 16, 1 + 20 mg/kg). The probability sum test (q test) was used to evaluate the synergistic action on BP reduction. In two-kidney, one-clip rats, the effects of amlodipine (1 mg/kg), telmisartan (6 mg/kg) and their combination on BP reduction were observed. In the chronic study, spontaneously hypertensive rats were treated with amlodipine (1 mg/kg), telmisartan (6 mg/kg), and their combination for 4 months. Histopathologic examinations were performed after the determination of BP and BP variability. There is a synergistic interaction between amlodipine and telmisartan on BP reduction. The optimal dose ratio was found at 1:6. The synergistic effect of this dose ratio (1:6) was also seen in two-kidney, one-clip rats. Long-term treatment with this combination results in a beneficial effect on the reduction of BP and BP variability. The end-organ damage, including myocardial hypertrophy, glomerular atrophy, and fibrosis, was significantly attenuated by this combination. The optimal dose ratio of amlodipine and telmisartan on BP was 1:6. This combination is beneficial for the BP and BP variability reduction and end-organ damage prevention.

Advances in Emerging Therapies 2010

In 2010, there were significant advancements in stroke prevention, whereas there were fewer studies that unearthed new ground on treatment of acute stroke and rehabilitation. We first discuss important pivotal studies in stroke prevention followed by acute treatment and rehabilitation. ### Prevention #### Homocysteine, Folic Acid, and B Vitamins Approximately 90% of all strokes are attributable to vascular risk factors.1 Homocysteine has also been identified as another risk factor for stroke. VITAmins TO Prevent Stroke (VITATOPS) aimed to assess whether daily administration of folic acid, vitamin B6, and vitamin B12 in patients with recent stroke or transient ischemic attack lowers homocysteine and reduces major vascular events. The data overall and pooled analysis of individual patient data showed that B vitamins have no or at most a marginal positive effect on reducing vascular events.2 #### Blood Pressure There is a correlation between blood pressure levels and risk of stroke. Data from Rothwell and colleagues now show that not only blood pressure levels, but also blood pressure variability account for stroke risk. A meta-analysis of antihypertensive drug trials found that calcium channel blockers and nonloop diuretic drugs were more effective than other antihypertensive agents to reduce blood pressure variability.3 Drug-class effects on interindividual variation in blood pressure can explain differences in effects of antihypertensive drugs on risk of stroke independently of their effects on mean systolic blood pressure. This means that the ideal antihypertensive agent should lower both blood pressure levels and variation in blood pressure to reduce stroke risk; however, we currently do not have such agents in our pharmacopeia for stroke prevention. #### Antithrombotic Drugs and Cerebrovascular Diseases New data have emerged on some age old questions about carotid dissection and intracranial stenosis. The use of aspirin or anticoagulation in spontaneous carotid artery dissection is a matter of debate with little data to guide decision-making. Data within a nonrandomized study suggest that the frequency …

Blood Pressure Variability

A series of articles1–4⇓⇓⇓ published recently in The Lancet and Lancet Neurology raise an interesting issue that has implications for both the clinical management of hypertension and future research in hypertension, particularly in the development and use of different classes of blood pressure (BP)–lowering drugs. These studies, which were led by Peter Rothwell at the John Radcliffe Hospital in Oxford, United Kingdom, suggest that, whereas there is undoubted and well-proven benefit in the current practice of reducing mean BP to prevent cardiovascular events, there may be additional benefit in also reducing BP variability (BPV), especially to prevent stroke. The studies suggest, moreover, that different classes of drugs are superior to others in reducing BPV (calcium channel blockers being best and the β-blocker atenolol being worst). However, these articles, by virtue of their sheer volume (≈50 pages of printed text and many pages of supplementary web appendix data), could overwhelm all but the most stoic readers, and misinterpretation of the data could lead to confusion and have an adverse effect on clinical practice. It is important, therefore, to assess the scientific reality and determine how attention to BPV might benefit patients with hypertension. In the first analysis, systolic BPV between visits and maximum BP reached in 4 cohorts of patients with previous transient ischemic attacks were strong predictors for subsequent stroke.1 In treated hypertensive patients in the Anglo-Scandinavian Cardiac Outcome Trial-Blood Pressure Lowering Arm systolic BPV between visits was also a strong predictor of stroke and coronary events independent of mean clinic or ambulatory BP measurement (ABPM). BPV on ABPM was a weaker predictor overall but was related to visit-to-visit variability. Traditional measures of variability, such as SD and coefficient of variation (CV), were used in these analyses, but one of the problems encountered in the …

Factors Associated With Day-By-Day Variability of Self-Measured Blood Pressure at Home: The Ohasama Study

We previously reported that high day-by-day blood pressure (BP) variability derived from self-measured BP at home (home BP) predicted cardiovascular mortality over and beyond other risk factors. The objective of this study is to clarify the determinants of the day-by-day home-BP variability. We conducted a cross-sectional community survey in 1,215 inhabitants (female gender 59%, mean age 62 years) of Ohasama, Japan. The subjects measured their BP and heart rate once every morning and once every evening for 4 weeks. The day-by-day BP variability and heart rate variability were defined as within individual standard deviation of all home BP and heart rate, respectively. We also considered coefficient of variation (CV). These parameters in the morning and those in the evening were calculated separately. The level and standard deviation of home systolic/diastolic BP (SBP/DBP) in the morning were 123.4 +/- 15.1/75.7 +/- 9.0 mm Hg and 8.6 +/- 3.1/5.8 +/- 2.0 mm Hg. Multivariate linear regression analysis demonstrated that older age, female gender, elevated home BP, low home heart rate, and elevated home heart rate variability were significant determinants of elevated home-BP variability. In addition to these factors, alcohol intake and sedentary lifestyle were also determinants of elevated home-BP variability in the evening. Day-by-day home-BP variability was associated with home BP, alcohol intake or sedentary lifestyle. Whether modifying these factors would reduce BP variability and whether such reduction would lead to better outcomes needs further study.

Clinical efficacy study on calming liver and restraining Yang formulain treating patients with mild or moderate degree of essential hypertension

To observe the therapeutic effect of calming the liver and restraining the Yang formula in treating patients with mild or moderate degree of essential hypertension (syndrome of hyperactivity of liver-Yang), and to explore its mechanism in lowering blood pressure. The 348 patients with EH of stage I , II were randomly divided into two groups, the 174 patients in the treated group were treated with the calming the liver and restraining the Yang formula, and the 174 patients in the control group were treated with amlodipine. The treatment course for them all was 12 weeks. The related clincial symptoms score and quality of life score estimated before and after treatment at 4th week, 8th week and 12th week were observed. Before and after treatment, the ambulatory blood pressure (AMBP), heart rate, blood lipid, serum livels of high-sensitivity C-reactive protein (Hs-CRP), Angiotensin-II (Ang II) and calcitonin gene-related peptide (CGRP) were measured respectively in 40 patients of the treared group and 40 patients of the control group. After treatment, the treatment in the treated group showed an effect better than that in the control group in terms of nigh-time blood pressure reducing rate (P < 0.05). The reducing blood pressure variability and total effective rate in the treated group were no significant than that in the control group. In respect of reducing symptomatic scores on dizzy, soreness and weakness of the waist and knees, disturbed and dry and bitter of mouth, ameliorating quality of life score, decreasing the levels of heart rate, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol(HDL-C) in the treated group were showing marked improvement as compared with that in the control group (P < 0.05 or P < 0.1). The improvement in the level of Ang II , Hs-CRP and CGRP before treatment in two groups were more significant than that after treatment (P < 0.05). However There were no difference in after treatment between the treated group and the control group. The calming the liver and restraining the Yang formula shows favorable efficacy in lowering blood pressure on the patients with mild or moderate degree of essential hypertension. It can reduce the clincial symptoms, improve the quality of life, regulate blood lipid metabolism. Its mechanism may be related to the functional relieving inflammatory reaction and inhibition the activity of renin-angiotensin-aldosterone system (RAAS).

Receptor Activity-Modifying Protein 1 Increases Baroreflex Sensitivity and Attenuates Angiotensin-Induced Hypertension

Calcitonin gene-related peptide (CGRP) is a powerful vasodilator that interacts with the autonomic nervous system. A subunit of the CGRP receptor complex, receptor activity-modifying protein 1 (RAMP1), is required for trafficking of the receptor to the cell surface and high-affinity binding to CGRP. We hypothesized that upregulation of RAMP1 would favorably enhance autonomic regulation and attenuate hypertension. Blood pressure, heart rate, and locomotor activity were measured by radiotelemetry in transgenic mice with ubiquitous expression of human RAMP1 (hRAMP1) and littermate controls. Compared with control mice, hRAMP1 mice exhibited similar mean arterial pressure, a lower mean heart rate, increased heart rate variability, reduced blood pressure variability, and increased baroreflex sensitivity (2.83+/-0.20 versus 1.49+/-0.10 ms/mm Hg in controls; P<0.05). In control mice, infusion of angiotensin II (Ang-II) increased mean arterial pressure from 118+/-2 mm Hg to 153+/-4 and 174+/-6 mm Hg after 7 and 14 days of infusion, respectively (P<0.05). In contrast, Ang-II hypertension was markedly attenuated in hRAMP1 mice with corresponding values of mean arterial pressure of 111+/-2, 119+/-2, and 132+/-3 mm Hg. Ang-II induced decreases in baroreflex sensitivity and heart rate variability, and increases in blood pressure variability observed in control mice were also abrogated or reversed in hRAMP1 mice (P<0.05). Moreover, during the Ang-II infusion, the pressor response to the CGRP receptor antagonist CGRP(8-37) was significantly greater (P<0.05) in hRAMP1 mice (+30+/-2 mm Hg) than in control mice (+19+/-2 mm Hg), confirming a significantly greater antihypertensive action of endogenous CGRP in hRAMP1 mice. We conclude that RAMP1 overexpression attenuates Ang-II-induced hypertension and induces a protective change in cardiovascular autonomic regulation.

Chronic ethanol attenuates centrally-mediated hypotension elicited via α 2-adrenergic, but not I 1-imidazoline, receptor activation in female rats

Aims This study dealt with the effect of chronic ethanol administration on hemodynamic responses elicited by α 2-adrenergic (α-methyldopa) or I 1-imidazoline (rilmenidine) receptor activation in telemetered female rats. Main methods The effects of α-methyldopa or rilmenidine on blood pressure (BP), heart rate (HR) and their variability were investigated in rats that received liquid diet without or with ethanol (5% w/v) for 12 weeks. To evaluate the effect of each drug on cardiovascular autonomic control (BP and HR variability) in the absence or presence of ethanol, three time-domain indices of hemodynamic variability were measured: (i) standard deviation of mean arterial pressure (SDMAP), (ii) standard deviation of beat-to-beat intervals, and (iii) root mean square of successive differences in R–R intervals. Key findings In liquid diet-fed control rats, i.p. rilmenidine (600 µg/kg) or α-methyldopa (100 mg/kg) reduced BP along with decreases and increases, respectively, in HR. Both drugs had no effect on HR variability but reduced BP variability (SDMAP), suggesting a reduced vasomotor sympathetic tone. Ethanol feeding attenuated reductions in BP and SDMAP evoked by α-methyldopa but not by rilmenidine. Significance We conclude that chronic ethanol preferentially compromises α 2- but not I 1-receptor-mediated hypotension in female rats probably via modulation of vasomotor sympathetic activity. These findings highlight the adequacy of rilmenidine use to lower BP in hypertensive alcoholic females.