Comparative efficacy and safety of oral antihypertensive agents in pregnant women with chronic hypertension: a network metaanalysis.

OBJECTIVE DATA: Chronic hypertension is associated with adverse perinatal outcomes, although the optimal treatment is unclear. The aim of this network metaanalysis was to simultaneously compare the efficacy and safety of antihypertensive agents in pregnant women with chronic hypertension. STUDY: Medline, Scopus, CENTRAL, Web of Science, Clinicaltrials.gov, and Google Scholar databases were searched systematically from inception to December 15, 2019. Both randomized controlled trials and cohort studies were held eligible if they reported the effects of antihypertensive agents on perinatal outcomes among women with chronic hypertension. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcomes were preeclampsia and small-for-gestational-age risk. A frequentist network metaanalytic random-effects model was fitted. The main analysis was based on randomized controlled trials. The credibility of evidence was assessed by taking into account within-study bias, across-studies bias, indirectness, imprecision, heterogeneity, and incoherence. RESULTS: Twenty-two studies (14 randomized controlled trials and 8 cohorts) were included, comprising 4464 women. Pooling of randomized controlled trials indicated that no agent significantly affected the incidence of preeclampsia. Atenolol was associated with significantly higher risk of small-for-gestational age compared with placebo (odds ratio, 26.00; 95% confidence interval, 2.61-259.29) and is ranked as the worst treatment (P-score=.98). The incidence of severe hypertension was significantly lower when nifedipine (odds ratio, 0.27; 95% confidence interval, 0.14-0.55), methyldopa (odds ratio, 0.31; 95% confidence interval, 0.17-0.56), ketanserin (odds ratio, 0.29; 95% confidence interval, 0.09-0.90), and pindolol (odds ratio, 0.17; 95% confidence interval, 0.05-0.55) were administered compared with no drug intake. The highest probability scores were calculated for furosemide (P-score=.86), amlodipine (P-score=.82), and placebo (P-score=.82). The use of nifedipine and methyldopa were associated with significantly lower placental abruption rates (odds ratio, 0.29 [95% confidence interval, 0.15-0.58] and 0.23 [95% confidence interval, 0.11-0.46], respectively). No significant differences were estimated for cesarean delivery, perinatal death, preterm birth, and gestational age at delivery. CONCLUSION: Atenolol was associated with a significantly increased risk for small-for-gestational-age infants. The incidence of severe hypertension was significantly lower when nifedipine and methyldopa were administered, although preeclampsia risk was similar among antihypertensive agents. Future large-scale trials should provide guidance about the choice of antihypertensive treatment and the goal blood pressure during pregnancy.

Augmentation strategies for inadequate antidepressant response: a review of placebo-controlled studies.

Uncontrolled trials of strategies directed at inadequate antidepressant response are prone to falsely positive results. Most of those studies which have used placebo control have assessed augmentation and the addition of lithium to tricyclic antidepressants or serotonin reuptake inhibitors has so far received the most support. A smaller literature shows promise for augmentation with triiodothyronine, pindolol and dehydroepiandrosterone.

[Assessment of anti-tremorogenic drugs--nicotine-induced tail-tremor model].

The repeated administration of nicotine at small doses, which do not produce whole body tremor or convulsion, causes tremor only in the tail (tail-tremor) of rats. The tremor is accompanied by locomotor hyperactivity without rigidity and immobility of the whole body, suggesting that the nicotine-induced tail-tremor model is useful for studying the mechanism underlying tremor associated with movement. The tail-tremor induced by nicotine was suppressed by mecamylamine, a nicotinic antagonist, but not by atropine or scopolamine, muscalinic antagonists. Moreover, the tail-tremor was suppressed by the beta-blockers propranolol and pindolol, as well as the benzodiazepines diazepam and clonazepam. Tremor at rest is observed only in Parkinson's disease, which is improved with anti-muscalinic drugs. Essential tremor is one of the typical tremors connected with movement (postural and kinetic tremor) and is improved with beta-blocker. These findings and results suggest that nicotine-induced tail-tremor is useful for the study of essential tremor in animal models.

Enhancement of the anticonvulsant effect of fluoxetine following blockade of 5-HT1A receptors.

Serotonin reuptake inhibitors, such as fluoxetine, have been shown to exert anticonvulsant effects in several animal models of epilepsy. In view of recent studies showing that 5-HT1A receptor antagonists (somatodendritic autoreceptor antagonists) enhance the increase in extracellular 5-hydroxytryptamine (5-HT, serotonin) produced by serotonin reuptake inhibitors, it was of interest to determine if these antagonists also enhance the anticonvulsant effect of fluoxetine in Genetically Epilepsy-Prone Rats (GEPRs). The 5-HT1A receptor antagonists (-)-pindolol and LY 206130 (1-[1-H-indol-4-yloxy]-3-[cyclohexylamino]-2-propanol maleate) were examined in the present study and both enhanced the anticonvulsant action of fluoxetine in severe seizure GEPRs (GEPR-9s). The latter effect of LY 206130 was found to be dose- and 5-HT-dependent. These findings provide further evidence that the increase in extracellular serotonin observed after administering fluoxetine in combination with a 5-HT1A receptor antagonist is physiologically important and that the anticonvulsant effect of fluoxetine in the GEPR is mediated through an increase in extracellular 5-HT.

[Fulminating malignant hyperthermia in swine--an alternative therapy concept]. / Die fulminante maligne Hyperthermie beim Schwein--Ein alternatives Therapiekonzept.

An inexpensive therapeutic concept compared to the dantrolene-therapy to counter the malignant hyperthermia (MH) is to be discussed, using a case-study from swine-anaesthesia. Hyperventilating the animals (with O2), administering metamizol, beta-blocker, bicarbonate and sufficiently cooling the patient can, if the symptoms are recognized early enough, arrest the hypermetabolic cascade in its track. All the animals that were treated according to this scheme survived the (MH) crisis without any lasting post operative damage.

Antihypertensive efficacy and side effects of three beta-blockers and a diuretic in elderly hypertensives: a report from the STOP-Hypertension study.

OBJECTIVE: To compare the blood pressure-lowering efficacy, the frequency of side effects and changes in laboratory values of three beta-blockers and a potassium-sparing diuretic combination in elderly hypertensive patients. DESIGN: The Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) was a prospective, randomized, double-blind, multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70-84 years. METHODS: The study group consisted of 1627 elderly hypertensive patients (mean +/- SD age 75.7 +/- 3.7 years; 37% males, 63% females). Supine and standing blood pressure, heart rate and side effects were recorded at each visit. Blood was drawn for routine analysis. The mean length of follow-up was 25 months (range 6-65). No patient was lost to follow-up. RESULTS: After 2-months' single-drug therapy, all four active drugs were found to be equally effective in reducing diastolic blood pressure (DBP). However, there were differences in their efficacy in reducing systolic blood pressure (SBP); the diuretic was significantly more effective than the beta-receptor blockers. The results of a series of multiple linear regression analyses showed that the observed differences in effect on SBP could not be explained by the different effects of the drugs on heart rate. More than two-thirds of the patients were given supplementary treatment, most of them already by the 2-month visit, after which there was no significant difference in blood pressure among the treatment regimens. The changes in laboratory values and in the prevalence of symptoms were minor for all four regimens. CONCLUSION: Metoprolol (controlled release), atenolol, pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP. There were differences in their efficacy in reducing SBP, the diuretic being more effective than the beta-blockers. After addition of supplementary treatment (beta-blocker to diuretic, or vice versa) there were no significant differences in blood pressure reduction among the groups. The changes in laboratory values and in the prevalence of symptoms were minor for all active treatment regimens. Thus, the satisfactory effect on cardiovascular morbidity and mortality was not impaired by low tolerability of the drugs.

[Electrocardiographic and echocardiographic changes during antihypertensive therapy]. / Modificazioni elettrocardiografiche ed ecocardiografiche durante terapia antipertensiva.

To investigate the changes of electrocardiographic and echocardiographic indexes of left ventricular hypertrophy (LVH) during antihypertensive therapy, 100 hypertensive patients, mean age 46 years, were studied in pretreatment condition and during 12 months of antihypertensive therapy. In pretreatment condition, 83 patients showed LVH by echocardiography (echo; left ventricular mass index greater than 130 g/m2) and 30 patients had LVH by electrocardiography (ECG) (Sokolow index greater than 35 mm). In comparison to echo index of LVH, Sokolow index showed a sensibility of 34% and a specificity of 88%. Both LV mass echo index and ECG index significantly decreased after 3 months but in different way. LV mass index mainly decreased after 12 months, whereas Sokolow index particularly decreased after 6 months, with no further changes in the subsequent months. After 12 months of therapy, the LV mass echo index normalized in 19% of the patients (16/83) and Sokolow index normalized in 57% (17/30). ECG sensibility and specificity, in comparison to LV mass echo, was 20% and 100%, respectively. Thus, ECG appears less sensitive than echo in the detection of LVH. During antihypertensive therapy ECG index of LVH normalized more precociously and to a greater extent than the echo index. However, the normalization of LVH by ECG does not necessarily mean that a complete anatomic regression of LVH has occurred.

Comparison of the antihypertensive efficiency of nitrendipine, metoprolol, mepindolol and enalapril using ambulatory 24-hour blood pressure monitoring.

In a randomized 6-month study of 201 patients, the antihypertensive efficiency of the calcium antagonist nitrendipine, the beta 1-selective blocker metoprolol, mepindolol, the beta blocker with intrinsic activity and the angiotensin-converting enzyme inhibitor enalapril were compared as monitored by 24-hour ambulatory blood pressure (BP) measurements. The study was designed so that a comparable decrease in casual BP values was obtained with all 4 drugs. If normotension was not achieved with monotherapy, a diuretic also was administered. Pretreatment casual BP and mean 24-hour ambulatory BP values did not differ between the 4 groups. Normotension as assessed by casual BP measurements was observed in all 4 groups after 6 months of therapy, there being no significant differences between the groups. However, significantly more diuretics were required in the mepindolol (n = 14) and in the enalapril (n = 20) groups compared to the nitrendipine (n = 5) and metoprolol (n = 7) groups. Despite comparable casual BP control, the 4 groups differed significantly in their mean 24-hour measurements. The greatest systolic and diastolic BP decreases were seen in the metoprolol group. Metoprolol was also the most effective drug in decreasing the frequency of systolic pressure peaks greater than 180 mm Hg. Both beta blockers and enalapril significantly decreased the morning BP increase compared to the values before treatment, while nitrendipine did not. These data show that casual BP measurement is not a good predictor of 24-hour BP in patients taking hypertensive therapy. Despite an equal degree of "office" BP control, different antihypertensive regimens do not confer the same degree of "nonoffice" BP control.

The use of carvedilol in elderly hypertensive patients.

Carvedilol, a beta-blocking drug with vasodilator activity, has been used in 4 studies in 107 elderly patients with essential hypertension and has reduced blood pressure effectively. In the first study the pharmacokinetics and clinical response were compared between 21 patients greater than 65 years of age and 8 patients aged 35-50 years). The peak blood levels, time to maximal concentration, area under the curve, half-life and trough level of the drug with chronic administration did not differ. The clinical responses to the drug were similar, with a greater fall in systolic blood pressure in the older group. However the initial systolic blood pressure in the older group was higher. Carvedilol was compared with metoprolol, pindolol and nitrendipine in elderly patients. The responses to carvedilol were at least equal to those obtained with the other drugs. Control was achieved in the three studies with once-daily therapy. There was no significant postural hypotensive effect. A feature of all studies was the large number of patients who responded to carvedilol. The side-effect profile of the drug was acceptable; headache and dizziness were more common than with placebo or the comparison drugs and were frequently associated. There were no adverse biochemical effects and the lipid profile was not altered. Carvedilol is an effective antihypertensive drug that lowers blood pressure equally well in the young and the old.

[24-hour blood pressure behavior in patients with untreated and treated hypertension in comparison with normotensive patients]. / 24-h-Blutdruckverhalten bei Patienten mit unbehandelter und behandelter Hypertonie im Vergleich zu normotonen Patienten.

Blood pressure was continuously monitored over 24 h in 201 patients with mild to moderate essential hypertension using a noninvasive method. Measurements were made both before and after 6 months of antihypertensive treatment and the data were compared to results from 100 normotensive patients. The frequency with which blood pressure values above 140/90 mm Hg occurred during the 24-h period proved to be the most reliable parameter for distinguishing between hypertensive and normotensive profiles. The blood pressures of all patients could be normalized (less than 140/90 mm Hg) on single or combined drug therapy as assessed by casual measurement. However, significant differences were observed between the 24-h profiles of the treated patients and the control group. The mean 24-h blood pressure, the mean day and nighttime blood pressures, the mean hourly pressure, and the frequency of increased blood pressure values were all significantly higher in the patients on medication as compared to the normotensive controls. This would suggest that normotension, as defined by the control group, cannot be attained with antihypertensive medication. In conclusion, 24-h continuous blood pressure monitoring allows a better evaluation of blood pressure profiles and consequently, will be of greater value in assessing cardiovascular risk than occasional random measurements.

[Beta receptor block versus calcium antagonism. A comparative study of bopindolol and nifedipine with special regard to quality of life]. / beta-Rezeptorblockade versus Kalzium-Antagonismus. Eine vergleichende Studie über Bopindolol und Nifedipin unter besonderer Berücksichtigung der Lebensqualität.

203 patients with a diastolic blood pressure higher than 100 mmHg were included in a randomized, double-blind trial to compare the antihypertensive efficacy of different daily dosages of bopindolol (Wandonorm) (0.05 mg, 0.5 mg, 1 mg, 2 mg) and nifedipine (2 x 20 mg). After 4 weeks of therapy blood pressure normalization could be achieved in 23.7% (0.05 mg), 32.5% (0.5 mg), 67.5% (1 mg), 64.1% (2 mg) and 59.0% (nifedipine) of the patients, respectively. In a subgroup of 159 patients the study was continued with an 8-week dose titration and a 16-week observation. At the end of the study blood pressure normalization was achieved in 91% and 94% of the patients treated with nifedipine and bopindolol, respectively. Most patients of the bopindolol-group needed 1 mg once daily as compared to those on the nifedipine who required 20 mg b.i.d. Because of intolerable side effects therapy was discontinued in 3 out of 162 patients on bopindolol and in 3 out of 41 patients on nifedipine. As compared to nifedipine the tolerance of bopindolol was judged significantly superior because tiredness and dizziness (32% vs 9%) and leg edema (20% vs. 6%) were recorded much more frequently in nifedipine treated patients. In 135 elderly patients "quality of life" was assessed upon by use of the "Nuremberg-Alters-Selbstbeurteilungs-Skala" (NAS), which refers to social contacts, mental and physical performance, sleep disturbances and general well-being.(ABSTRACT TRUNCATED AT 250 WORDS)

[Ambulatory continuous 24-hour blood pressure monitoring in the diagnosis and therapy of arterial hypertension and modification by the antihypertensive agents enalapril, metoprolol, mepindolol and nitrendipine]. / Ambulante kontinuierliche 24 h Blutdruckregistrierung in der Diagnostik and Therapie der arteriellen Hypertonie und die Beeinflussung durch die Antihypertensiva Enalapril, Metoprolol, Mepindolol und Nitrendipin.

After improvement of technical equipment continuous ambulatory blood pressure monitoring is more and more used in the diagnosis of hypertension. New fully automatic systems permit a reliable registration and evaluation of 24-h blood pressure profiles. Typical circadian rhythmics of blood pressure, independent of a variability with different grades of activity, can be demonstrated in normotensive persons and also in patients with essential hypertension. Patients with secondary forms of hypertension show a nivellation or offset of circadian blood pressure rhythmics. A study was performed to examine the antihypertensive efficacy of the calcium antagonist Nitrendipine, the beta 1-adrenoceptor-selective blocker Metoprolol, the beta-blocker with intrinsic activity Mepindolol and the angiotensin converting enzyme inhibitor Enalapril in patients with mild to moderate hypertension over a period of 6 month. Continuous ambulatory blood pressure monitoring was performed before and after 6 month of therapy. 98 of 299 included patients broke off therapy, 47 of those because of side effects. Hydrochlorothiazide was given additionally if the antihypertensive effect of monotherapy was not sufficient after a period of 4 weeks. Morning blood pressure controls at the end of the treatment period showed normotensive values in all groups without significant differences between the groups before and at the end of the treatment period. The number of prescriptions of diuretics necessary to achieve normotension differed between the four treatment groups: Nitrendipine (n = 5), Metoprolol (n = 7), Mepindolol (n = 14), Enalapril (n = 20). In contrast to the morning blood pressure values the continuous 24-h blood pressure monitoring demonstrated significant differences between the therapy groups. Metoprolol turned out as most effective in lowering blood pressure and in reducing the number of systolic blood pressure peaks above 180 mmHg, but on the other hand showed the highest incidence of relative hypotension (less than 100 mmHg systolic, less than 80 mmHg diastolic). Mepindolol demonstrated a significant lower efficacy. In the Nitrendipin group least of all prescriptions of diuretics were necessary and the lowest number of hypotensive systolic blood pressure values occurred. Enalapril showed the most significant reduction of diastolic values above 100 mmHg and the lowest number of diastolic values below 80 mmHg, but the highest number of prescription of diuretics was necessary in the Enalapril group. In none of the four therapy groups a neutralisation of circadian blood pressure rhythmics was demonstrable.

Effects of bopindolol on renal function.

The effect of the long-acting beta-blocking agent bopindolol on renal function was assessed in 10 healthy normotensive volunteers and 10 hypertensive patients. The subjects received 1 mg bopindolol at 8 p.m. for 21 days. The following determinations were made at 8 a.m. on recumbent, fasting subjects before day 0 (D0) and 12 h after day 1 (D1) the first dose of bopindolol, and on the 21st day of treatment (D21): blood pressure (diastolic = DBP), glomerular filtration rate (GFR) and renal plasma flow (RPF) as reflected by the plasma disappearance of 51Cr-EDTA and 125I-hippuran, plasma concentrations and 2- and 24-h urinary excretion of electrolytes, creatinine, and proteins and osmolality of the urine. Plasma renin activity was assessed on standing subjects. Following bopindolol administration GFR, RPF, and filtration fraction remained stable, in spite of a fall of DBP from 80 +/- 7 to 76 +/- 4 and to 72 +/- 9 mm Hg in normotensives (p less than 0.05) and from 106 +/- 11-96 +/- 10 and to 91 +/- 8 mm Hg in hypertensives (p less than 0.05) on D1 and D21, respectively. The drops in DBP at D1 correlated weakly with the pretreatment renin levels (p = 0.074, p less than 0.05). All the other variables remained stable, including diuresis, free water clearance, and fractional sodium excretion. It is concluded that in contrast to many other anti-hypertensive drugs including several beta blockers, bopindolol does not reduce renal function during short- or medium-term treatment in normal volunteers or hypertensive patients.

First-step treatment of mild to moderate uncomplicated essential hypertension by a new calcium antagonist: nicardipine.

Nicardipine, a new calcium antagonist, was tested in a 14-week double-blind trial including 15 outpatients with uncomplicated essential hypertension. They were randomly assigned to nicardipine (20-30 mg three times daily) or placebo as first-step treatment. When necessary but always after a minimum of 4 weeks, pindolol (15 mg/day) was combined with nicardipine or placebo. At the end of step 1 (85 +/- 6 days with nicardipine vs. 58 +/- 6 days with placebo, p less than 0.01), nicardipine induced larger drops in supine systolic and diastolic blood pressure (SBP and DBP) than the placebo (21 +/- 2.5 vs 1.4 +/- 3 mm Hg, p less than 0.001, and 13 +/- 2 vs. 3.5 +/- 1.5 mm Hg, p less than 0.001, respectively). In the nicardipine group (n = 57), 53% of patients had controlled blood pressure (SBP less than 160 mm Hg and DBP less than 95 mm Hg) versus 17% in the placebo group (n = 47), p less than 0.001. There was no significant correlation between the decrease in blood pressure and the age of patients. The most common side effects in the nicardipine group were flushes (12%), headache (8%), ankle edema (5%), and asthenia (4%). When blood pressure was not brought under control and pindolol was prescribed as the second-step treatment, the nicardipine group (n = 52) displayed larger drops in SBP and DBP than the placebo group (n = 40) (27 +/- 5 vs. 15 +/- 3 mm Hg, p less than 0.01, and 18 +/- 1 vs. 9 +/- 2 mm Hg, p less than 0.001, respectively). These results show that a calcium antagonist is useful for first-step treatment of hypertension.

Effect of pindolol on potassium homeostasis in patients with essential hypertension.

A study of the effects of pindolol on potassium homeostasis was undertaken in 25 patients (19 women, 6 men) with essential hypertension. The patients were maintained on their usual diet and were withdrawn from antihypertensive therapy for three weeks before the study began. They were then randomly assigned to one of three treatment groups: (a) pindolol, 15 mg daily; (b) hydrochlorothiazide, 50 mg daily; and (c) both drugs combined. Total body potassium (TBK), urine aldosterone excretion, and plasma renin activity (PRA) were measured after eight weeks of therapy and compared with pretreatment values. Mean PRA remained unchanged in patients taking only pindolol or the drug combination, but it rose significantly in patients taking only hydrochlorothiazide. Mean urine aldosterone concentrations fell in patients taking only pindolol, rose in those taking only hydrochlorothiazide, and remained unchanged in those taking the combination. Mean TBK concentrations rose significantly in patients taking only pindolol or the combination, and fell significantly in those taking only hydrochlorothiazide. The rise in TBK concentrations with the combination clearly suggests that pindolol offsets the potassium wastage induced by diuretics, though probably by a mechanism outside the renin-aldosterone system. Because of this rise, it may be possible to eliminate potassium supplementation in patients taking the combination pindolol and hydrochlorothiazide.

Effect of pindolol and nifedipine alone and in combination on haemodynamic parameters/variables in essential hypertension.

Thirteen patients with essential hypertension were started on pindolol 10-20 mg daily and twelve on nifedipine 20-60 mg daily. At the end of 6 weeks inadequate responders (B.P. greater than 140/90) were put onto combined treatment with both drugs, ten of the pindolol and six of the nifedipine patients being affected. Combined therapy then continued for a further 6-week period, while adequate responders (B.P. less than 140/90) continued with their initial drug. In addition to blood pressure, heart rate and cardiac index were also measured, and total peripheral resistance index was calculated. Where blood pressure decreased below 140/90 at the end of 12 weeks in patients on combined treatment, the original drug was withdrawn, leaving the patient on a single-drug regimen again, this time with the 'second compound'. This manoeuvre was followed by a rise in blood pressure in five out of eight patients in whom pindolol was withdrawn and in two out of six after nifedipine withdrawal. No definite conclusions can be drawn from these findings, and it may be that a better approach to the problem of poor responders would be to try each drug on its own before combining them, rather than combining first and then withdrawing the initial treatment. The increased peripheral resistance typical of essential hypertension was not adversely affected by either drug, while combined treatment had a beneficial effect on this parameter.

[Controlled randomized double-blind study for the comparison of the treatment of patients with essential hypertension with homeopathic and with pharmacologically effective drugs]. / Kontrollierte randomisierte doppelblinde Studie zum Vergleich einer Behandlung von Patienten mit essentieller Hypertonie mit homöopathischen und pharmakologisch wirksamen Medikamenten.

In a randomized double-blind cross-over study the effects of antihypertensive pharmacotherapy were compared with those of homeopathic treatment in 10 patients with essential hypertension. The conclusions are: 1. The blood pressure lowering effect under pharmacotherapy is clearly superior to that under homeotherapy, where it was negligible and statistically not significant. 2. As far as improvement of subjective complaints of the patients is concerned there was no superiority of pharmacotherapy over homeopathic treatment. 3. The cross-over design appears less suitable than, perhaps, a design with parallel treatment groups because of the long duration of such a study and the observed carry-over effect.

Renal function, body fluid volumes, renin, aldosterone, and noradrenaline during treatment of hypertension with pindolol.

Sixteen hypertensive patients received pindolol (10-45 mg/day); mean +/- SD, 28.75 +/- 15.22) for 3-8 weeks in a placebo-controlled, single-blind, crossover study. Supine and standing blood pressures (BP) were lowered, whereas effective renal plasma flow and glomerular filtration rates (estimated from the clearances of Hippuran and EDTA during oral water loading) did not change consistently. "Blood volume" (calculated from 125I-human serum albumin space and microhaematocrit) increased, with a corresponding reduction in serum albumin but without a change in body weight or "total body water" (T2O space). The results suggest a transfer of water from the interstitial to the intravascular compartment. This was supported by estimates of "extracellular fluid volume" (EDTA space) and "interstitial volume" (EDTA) minus human serum albumin spaces) in 3 subjects. The changes produced in "blood volume" correlated with those in BP. Plasma levels of noradrenaline, renin activity, and aldosterone were reduced, as was renal aldosterone excretion. There was no correlation between the changes produced by pindolol in BP and these hormone levels. Pindolol treatment reduced serum calcium concentration. There was a strong positive correlation between changes in BP and serum calcium and renal calcium excretion.