Different Secretion Patterns of Adrenomedullin,Brain Natriuretic Peptide,and Atrial Natriuretic Peptide During Exercise in Hypertensive and Normotensive Subjects

The purpose of this study was to investigate the effect of exercise on plasma concentrations of adrenomedullin, brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) in patients with essential hypertension (n=15) and in normotensive controls (n=10). Exercise consisted of two fixed workloads, 40 and 80 watts of work load using a supine bicycle ergometer. Plasma levels of all three peptides at rest were significantly higher in hypertensives than in controls. Plasma concentrations of ANP increased with exercise in both groups and had greater     

Patterns of neuroendocrine activation at rest and during exercise following acute myocardial infarction

Previous studies of neurohumoral activation following myocardialinfarction have concentrated on the within-hospital phase andhave only made measurements at rest. The objectives of thisstudy were to measure neuroendocrine activity in the early convalescentphase of myocardial infarction at rest and during symptom-limitedmaximal exercise and to study the effects of early drug therapy.We studied 75 patients, mean age 57 (range 37–74) withoutevidence of overt heart failure, following Q-wave myocardialinfarction. Patients were studied a mean of 17 days followingmyocardial infarction and compared with 11 age-matched controlsubjects. Plasma nor adrenaline, adrenaline, atrial natriureticpeptide and plasma renin activity were measured at rest, atsubmaximal and symptom-limited maximal treadmill exercise. Atthe time of study 40 patients were taking beta-blockers, 19diuretics and 16 no treatment. Atrial natriuretic peptide levelswere higher at rest (P=0.0001) and at symptom-limited exercise(P=0.002) in the patient group than in the control subjects.Although there were no significant resting differences betweenthe patient subgroups, at symptom-limited exercise plasma atrialnatriuretic peptide levels were significantly higher in thepatients taking beta-blockers than in the other patient groups(P=0.001). Plasma renin activity was no different between thepatients and the control subjects at rest or during exercise.Those patients taking diuretics had higher values at rest (P=0.001)and during exercise (P = 0.005) compared with the remainingpatients. There were no significant differences in resting ormaximal exercise levels of plasma noradrenaline and adrenalinebetween the patients and the control subjects (all P>0.1).However, catecholamine levels were higher in the patients atsubmaximal workloads (P<0.005). The neurohumoral responsehas largely resolved at rest 17 days following myocardial infarctionbut continued activation persists during exercise.     

非洛地平与倍他乐克联用对高血压病心肌缺血的疗效观察

目的：观察非洛地平与倍他乐克联用对高血压病伴心肌缺血的疗效。　方法：对 ３２ 例高血压病伴心肌缺血患者运用踏车心电图运动试验观察比较应用非洛地平与倍他乐克联用的疗效,运用 ２４ 小时动态心电图和动态血压同步监测客观评价联用的效果。　结果：踏车心电图运动试验显示非洛地平和倍他乐克联用后进一步使总运动时间延长 １６％ , Ｓ Ｔ段最大压低深度减少 ２０％ ;最大工作负荷下降 １１％ （ Ｐ＜ ０．０５～０．００１）;联合用药后 ２４ 小时动态心电图监测显示 Ｓ Ｔ段压低总时间减少 ６７％ ,最大压低深度减少 ４６％ ,复杂室性心律失常发生率减少 ２６％ ,平均心率减低 １４％ （ Ｐ＜ ０．０１～０．００１）;２４ 小时动态血压监测显示具有良好的降压作用和谷峰比值。　结论：两药联合应用有良好降压作用和更好的抗心肌缺血效应。     

Body Composition,Intraerythrocyte Sodium Content,Volume Regulation and Blood Pressure during Moderate Sodium Restriction in Hypertensive Men

ABSTRACT. Eleven moderately obese middle-aged male outpatients with untreated mild hypertension reduced their sodium intake by about 120 mmol per day during 4–6 weeks. Diastolic blood pressure was then significantly reduced in comparison with a matched control group. The reduction of urinary sodium excretion was significantly correlated to the change in mean arterial pressure. Mean body mass showed a small significant decrease, although there were no significant changes in total body water or body fat as determined from measurements of ⁴⁰K and tritiated water. Nor did mean extracellular water or plasma volume (Evan's blue) show any significant change. The decrease in urinary sodium excretion was associated with increases in plasma renin activity and urinary aldosterone excretion, while a sympathetic nervous natriuretic index (urinary dopamine to noradrenaline excretion ratio) decreased. The low sodium diet period was followed by a period of energy reduction as well as sodium restriction for 15 weeks. Mean body mass was then reduced by about 8 kg. The systolic but not the diastolic blood pressure showed a significant decrease. The intraerythrocyte content of water, sodium and potassium did not change significantly during any of the diet periods. We conclude that moderate sodium restriction lowered the blood pressure and affected the renin-aldosterone and sympathetic nervous system to retain sodium which might explain the constancy of the plasma volume.     

A Comparison of 100 mg Atenolol and 100 mg Metoprolol Once a Day at Rest and during Exercise in Hypertensives

Abstract The effects of once daily dosage of the two cardioselective β-adrenoceptor blocking agents, atenolol and metoprolol, were studied in 26 patients with primary hypertension. The study was a randomized double-blind cross-over trial with placebo run-in and wash-out. Assessment of effect was performed about 1 and 25 hours after dosing. At rest, both atenolol and metoprolol lowered the blood pressure (BP) and heart rate (HR) compared to placebo. Atenolol induced a more effective BP reduction than metoprolol, especially 25 hours after drug intake. During exercise 1 hour after dosing both drugs reduced BP and HR to a similar extent, whereas 25 hours after dosing atenolol gave a more efficient BP and HR reduction than metoprolol. Our data show that both 100 mg atenolol and 100 mg metoprolol are effective antihypertensive β-blockers at rest and during exercise, 1 hour after intake. Metoprolol was less effective than atenolol 25 hours after dosing probably due to its shorter plasma half-life, thus implying a twice daily regimen for metoprolol in standard preparation.     

美托洛尔对高血压患者生活质量的影响

目的观察美托洛尔治疗对患者生活质量的影响。方法７４例高血压患者服用美托洛尔８周，通过８项生活指标观察患者在治疗过程中影响。结果美托洛尔降压治疗显效率、总有效率分别为６１．２％及７８．４％，其中Ｉ、Ⅱ期高血压疗效更好。生活质量评定显示，经８周治疗患者在躯体症状、工作能力、生活满意感及业余生活等方面均有显著改善（Ｐ＜０．０５～０．０１）。结论美托洛尔在降压治疗同时可明显改善患者生活质量     

Hormonal effects of the diuretic xipamide in healthy men

The effect of xipamide on plasma alpha-atrial natriuretic peptide and the renin-aldosterone-kallikrein system have been studied in 12 healthy men, using a double-blind cross-over design. After a run-in period on placebo of 1 week, the subjects were treated with either placebo (n = 6) or xipamide 20 mg once daily (n = 6) for 16 weeks and were then switched to the alternative medication for another 16 weeks. The plasma concentration of alpha-atrial natriuretic peptide fell after 1 week of xipamide administration and increased during prolonged xipamide administration but remained reduced. The changes in plasma alpha-ANP observed after 1 week of xipamide were negatively correlated with the changes in hematocrit and hemoglobin. Plasma renin activity (PRA), aldosterone concentration (PAC), and urinary excretion of aldosterone and kallikrein increased after 1 week of xipamide administration, levelled off during the second and fourth weeks, but remained elevated during further prolonged xipamide administration for 16 weeks. The xipamide-induced changes in PRA and PAC were positively correlated with the changes in the hematocrit and hemoglobin. The changes in plasma renin, aldosterone, and alpha-atrial natriuretic peptide during xipamide administration may be related to diuretic-induced volume contraction.     

硝苯地平和卡托普利对高血压患者血浆、唾液、尿液心钠素浓度的影响

目的探讨心钠素（ＡＮＰ）在高血压发病中的作用。方法５２例原发性高血压（ＥＨ）患者，随机分组，应用硝苯地平或卡托普利治疗２周前后，测定血浆、唾液、尿液ＡＮＰ含量的变化，并与健康组对照。结果治疗前患者血浆、唾液、尿液中ＡＮＰ均高于对照组（Ｐ＜０．０１）。治疗２周后，高血压组ＳＢＰ、ＤＢＰ和血、唾液、尿液中ＡＮＰ较治疗前明显降低（Ｐ＜０．０１），而治疗组间比较差异无显著性（Ｐ＞０．０５），且唾液和尿液中ＡＮＰ与血浆中浓度有同样变化趋势。结论硝苯地平和卡托普利可能是通过抑制ＡＮＰ的产生和释放的某个环节而发挥其降压效果的。     

Ambulatory Monitoring of Blood Pressure and Arrhythmias by non-invasive methods in Hypertensive Patients Treated with Metoprolol

Non-invasive ambulatory monitoring of blood pressure and ECG was employed to assess the 24-hour profile of blood pressure and arrhythmias in 20 out-patients aged 31–69 years. The technique was further used to measure the therapeutic response to 100 mg once daily of the cardioselective beta-blocker metoprolol. The basal ambulatory examinations revealed that all 20 patients had a mean 24-hour blood pressure of >160/90 mm Hg, corresponding to a mean arterial pressure (MAP) of > 113 mm Hg. In 16 of the 20 patients (80%) the mean 24-hour MAP was reduced to below 113 mm Hg. Addition of diuretics in the remaining four patients further decreased the mean 24-hour MAP to < 113 mm Hg, which confirmed by a third ambulatory examination. The ECG recordings in the initial ambulatory study revealed severe degrees of ventricular arrhythmias in 7 patients. After treatment with metoprolol, all of them presented an improved ECG picture.     

盐敏感性高血压病患者血浆心钠素、血管紧张素Ⅱ和醛固酮水平测定及苯那普利治疗的初步观察

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Felodipine or Hydrochlorothiazide/Triamterene for Treatment of Hypertension in the Elderly: Effects on Blood Pressure, Hypertensive Heart Disease, Metabolic and Hormonal Parameters

Trenkwalder P, Plaschke M, Aulehner R, Lydtin H. Felodipine or Hydrochlorothiazide/Triamterene for Treatment of' Hypertension in the Elderly: Effects on Blood Pressure, Hypertensive Heart Disease, Metabolic and Hormonal Parameters.

The aim of the study was to compare the antihypertensive efficacy of either felodipine or the diuretic combination hydrochlorothiazide/triamterene in a group (n = 65) of elderly (≥70 years) hypertensives (office blood pressure ≥ 60/95 mmHg) with special regard to ambulatory blood pressure monitoring, hypertensive heart disease and metabolic parameters. This was a randomized, double-blind study with a treatment period of 6 months. Reduction of office and 24-hr ambulatory blood pressure was comparable with both treatment regimens; after 6 months, 18 of 29 patients in the felodipine group (62%) and 20 of 27 patients in the diuretic group (74%; p = 0.4) were controlled. While episodes of ischemic type ST-segment depression were significantly reduced in the felodipine group (from 49 to 9 episodes), there was no significant change in the diuretic group (from 24 to 21 episodes). Both regimens decreased left ventricular wall thickness, but the decline in left ventricular muscle mass index was significant only for felodipine. Felodipine did not induce any change in metabolic or hormonal parameters; the diuretic combination significantly increased serum creatinine, uric acid, plasma renin activity, and plasma prorenin. Thus, the antihypertensive efficacy of felodipine and the diuretic combination was comparable in elderly hypertensives; only felodipine, however, improved parameters of hypertensive heart diesease and showed a neutral metabolic and hormonal profile.     

Insulin-induced hypoglycaemia increases plasma concentrations of angiotensin II and does not modify atrial natriuretic polypeptide secretion in man

Summary Insulin-induced hypoglycaemia causes profound haemodynamic changes, commonly ascribed to catecholamine increase. The aim of the present study was to investigate the influence of insulin-induced hypoglycaemia on nonadrenergic factors potentially involved in haemodynamic regulation: angiotensin II and alpha-human atrial natriuretic polypeptide. Fourteen healthy male subjects, aged 25.5±0.74 years, body mass index 23.81±0.68 kg/m², received (after an overnight fast and at least 60 min rest in a supine position) an i.v. bolus injection of human regular insulin (Actrapid HM, Novo, Bagsvaerd, Denmark: 3.84 U/m²). Serial venous blood samples were drawn in the following 150 min, to measure plasma glucose, angiotensin II, alpha-human natriuretic polypeptide, and factors potentially involved in the regulation of the renin-angiotensin-aldosterone system. During the study, we observed a plasma glucose fall, reaching a nadir of 1.95±0.11 mmol/l between 25 and 30 min, and an increase of angiotensin II (from 7.6±0.8 to 13.5±1.1 pg/ml, p = 0.01, quadratic model evaluated by an analysis of the variance for repeated measures), whereas atrial natriuretic polypeptide remained unchanged. As far as the regulation of the renin-arigiotensin-aldosterone system is concerned, the increase of angiotensin II is attributable to the increased plasma renin activity, whereas angiotensin converting enzyme was not modified. The increase of plasma renin activity, in turn, is attributable both to the increased catecholamine concentrations and to the decreased potassium levels. Both adrenocorticotropic hormone and angiotensin II are potentially involved in the hypoglycaemia-induced increase of aldosterone concentrations.     

Relationships Between Biomarkers and Left Ventricular Filling Pressures at Rest and During Exercise in Patients After Myocardial Infarction

BackgroundIncreased pulmonary capillary wedge pressure (PCWP) is an independent prognostic predictor after myocardial infarction (MI), but PCWP is difficult to assess noninvasively in subjects with preserved ejection fraction (EF). We hypothesized that biomarkers would provide information regarding PCWP at rest and during exercise in subjects with preserved EF after MI.Methods and ResultsSeventy-four subjects with EF >45% and recent MI underwent right heart catheterization at rest and during a symptom-limited semisupine cycle exercise test with simultaneous echocardiography. Plasma samples were collected at rest for assessment of midregional pro–A-type natriuretic peptide (MR-proANP), N-terminal pro–B-type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), copeptin, and midregional pro-adrenomedullin (MR-proADM). Plasma levels of MR-proANP and PCWP were associated at rest (r = 0.33; P = .002) and peak exercise (r = 0.35; P = .002) as well as with changes in PCWP (r = 0.26; P = .03). Plasma levels of NT-proBNP and PCWP were weakly associated at rest (r = 0.23; P = .03) and peak exercise (r = 0.28; P = .02) but not with changes in PCWP (r = 0.20; P = .09). In a multivariable analysis, plasma levels of MR-proANP remained associated with rest and exercise PCWP (P < .01), whereas NT-proBNP did not. Plasma levels of Gal-3, copeptin, and MR-proADM were not associated with PCWP at rest or peak exercise.ConclusionsIn subjects recovering from an acute MI with preserved EF, plasma levels of natriuretic peptides, particularly MR-proANP, are associated with filling pressures at rest and during exercise.     

Role of Hypervolemia and Renin in the Blood Pressure Control of Patients with Pyelonephritic Renal Scarring

ABSTRACT Patients with pyelonephritic renal scarring are at risk of developing renal failure and hypertension. We studied glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF), systolic (SBP) and diastolic (DBP) blood pressure, fractional sodium, potassium and phosphate excretion, peripheral renin activity (PRA), plasma aldosterone (p-Aldo), urinary albumin excretion (U-Alb) and urinary β₂-microglobulin excretion (β₂-M) in hydropenia and during transition to 3% volume expansion with isotonic saline infusion in 22 female patients with renal scarring due to pyelonephritis and 9 healthy controls. The patients had significantly lower GFR, higher SBP and higher PRA in hydropenia, but there was no significant difference in RPF, FF, DBP or p-Aldo. After volume expansion, SBP, DBP, PRA and p-Aldo were significantly higher in patients than in controls. Transition to 3% volume expansion was associated with a similar increase in SBP in both patients and controls, whereas DBP increased significantly more in the patients (p<0.01). Volume expansion resulted in a significant suppression of PRA and p-Aldo in both patients and controls. The patients with renal scarring had the same capacity to excrete sodium and water during transition to volume expansion as the healthy controls. The renin-aldosterone system seems abnormally activated and is probably more important than hypervolemia in the development of hypertension in this group of patients.     

Comparison of Impedance Cardiography and Thermodilution-Derived Measurements of Stroke Volume and Cardiac Output at Rest and During Exercise Testing

Background: Non-invasive evaluation of haemodynamic variables remains a preferable and attractive option in both pharmacologic research and clinical cardiology.Objectives: The objective of this study was to evaluate the correlation, feasibility and diagnostic value of haemodynamic measurements by ICG with the thermodilution (TD) method at rest and during exercise testing.Methods: We measured stroke volume (SV) and cardiac output (CO) with both methods in 20 patients with suspected coronary artery disease (CAD). All measurements were performed simultaneously at rest and during bicycle exercise.Results: There was a highly significant correlation (p < 0.001) for measurements of SV between both methods at rest (r = 0.83) and during exercise (r = 0.85–0.87) with 50–100 watts. For measurements of CO, the respective correlations were r = 0.85 at rest and r = 0.92–0.94 during exercise. The mean difference for measurements of SV were 3.8 ± 12.6 ml at rest and 6.5± 11.4 ml during exercise. For measurements of CO, the mean difference between both methods was 0.9 ± 1.0 l/min at rest and 1.0± 0.8 l/min during exercise. Compared to TD measurements, ICG had a bias to overestimate SV and CO of approximately by 5–10%. One patient had to be excluded because of inappropriate quality of the ICG signals during exercise.Conclusions: ICG is a feasible and accurate method for non-invasive measurements of SV and CO. Haemodynamic measurements by ICG were correlated highly significant to simultaneous measurements by the TD method.     

Venous Volume and Blood Flow in Hand at Rest and during Psychological Stress in Male Relatives to Hypertensive Patients

ABSTRACT. A total of 19 male relatives to hypertensive individuals were examined with regard to blood flow and venous volume in the hand at rest and during a psychological stress test. They were compared to 19 male controls without heredity for hypertension. There were no significant differences between the groups in hand blood flow or venous volume either at rest or during the test. The increase in vascular resistance during psychological stress was significantly higher in relatives than in controls. Possible mechanisms behind the differences in arterial vascular reactivity between the groups are discussed.     

美托洛尔治疗高血压对血脂及糖代谢的影响

对37例原发性高血压患者进行美托洛尔治疗前后心率、血压、总胆固醇、甘油三酯、糖耐量试验、胰岛素、24h尿钾、钠、钙、肌酐测定，结果表明：服用美托洛尔后心率、血压下降，尿钠排泄增加，糖负荷曲线略增高，胰岛素水平及胰岛素抗性（ISR）降低（P＜0．01），血脂无改变（P＞0．05）。提示美托洛尔对原发性高血压Ⅰ，Ⅱ期者，在改善血压、心率同时，不影响脂肪代谢，可增加尿纳排泄，对糖代谢、胰岛素及胰岛素抵抗影响较小。     

美托洛尔对高血压患者左室肥厚及心功能的影响

对高血压病患者54例应用美托洛尔口服，血压稳定后改为维持量随访观察治疗3～4个月，HR，SBP，DBP，MAP及TPR均降低（P＜0．01），总有效率为87％；左室形态结构指标（LAD，LVD，LVMI）显著改善（P＜0．05～0．01）；左室舒张功能指标（A，E，A／E，PFR及NPFR）显著改善（P＜0．05）；左室收缩功能指标（SV，EF及CO）无变化（P＞0．05）。     

Dissociation of Plasma Atrial Natriuretic Peptide Responses to Upright Posture and Furosemide Administration in Patients with Normal-, Low Renin Essential Hypertension and Primary Aldosteronism

Plasma levels of atrial natriuretic peptide (ANP) were measured in patients with normal renin essential hypertension (n = 12), low renin essential hypertension (n = 11) and primary aldosteronism due to aldosterone producing adenoma (APA, n = 8) and idiopathic hyperaldosteronism (IHA, n = 3) after overnight rest in the supine position and after 4 h upright posture and furosemide administration. Plasma renin activity (PRA) and aldosterone (Aldo) levels were also determined. Compared to normal renin essential hypertension (33.6± 2.2 pg/ml), basal plasma ANP was significantly higher in low renin essential hypertension (66.8± 6 pg/ml), IHA (54.1± 6.3 pg/ml) and APA before (62.4± 4.9 pg/ml) but not after adrenal surgery (22± 3 pg/ml). After upright posture and furosemide administration plasma ANP was decreased (p < 0.01) in patients with low renin and, less markedly, with normal renin essential hypertension, however not in IHA and APA. In about half of the patients with low renin essential hypertension, unchanged PRA after upright posture and furosemide administration was associated with increased plasma Aldo and decreased ANP levels. We conclude that (i) the relatively high basal plasma ANP levels in low renin essential hypertension, IHA and APA may reflect the presence of volume expansion in these patients; (ii) the hormonal responses to upright posture and furosemide administration in patients with normal and low renin essential hypertension may indicate a counterregulatory role of ANP during activation of the renin-angiotensin-aldosterone system; (iii) the high plasma ANP, which is unresponsive to upright posture and furosemide administration, in patients with APA and IHA may be a potentially interesting new finding whose pathophysiological significance remains to be established.