Phaeochromocytoma was diagnosed in 77 (0.36%) of 21,420 hypertensive patients examined in the hypertension units of the Broussais and Saint-Joseph hospitals, Paris, between 1976 and 1986. Our diagnostic strategy is to reserve biochemical examinations to cases with suspected phaeochromocytoma and to explore only those patients who have positive laboratory results. Patients suspected of harbouring a phaeochromocytoma are those who complain of headaches, palpitations and sweating (these 3 symptoms together having a 90.9% sensitivity and a 99.9% exclusion value), those who have a family history of phaeochromocytoma or who present with medullary thyroid carcinoma or phakomatosis, or those who do not respond to anti-hypertensive treatments. Altogether, these patients account for less than 10% of all cases of hypertension. The most sensitive test in this group is measurement of urinary metanephrines. Among 30 patients with phaeochromocytoma in whom urinary metanephrines and plasma noradrenaline were measured on the same day, none had urinary metanephrine values lower than 3.69 mumol/24 h (0.7 mg/24 h) while 6, who had normal blood pressure at the time of sampling, had noradrenaline levels below 3.53 nmol/l (600 pg/ml). Prior to surgery, the tumour was correctly located by urography (69% of 58 n = tumours), ultrasounds (74%, n = 38), arteriography (83%, n = 23), radioisotope scanning (91%, n = 32), computed tomography (95%, n = 40) and nuclear magnetic resonance imaging (12/12). In 28 patients who had both radioisotope scanning and computed tomography the sensitivities of these examinations were 90% and 100% respectively. A stage by stage approach to the diagnosis of phaeochromocytoma, using detection criteria followed by biochemistry then location methods, is an economical strategy with the best yield from diagnostic and imaging techniques.

Adrenal Gland Neoplasms↗

PubMed1987

[Ambulatory blood pressure in normotensive subjects. Definition of reference values as a function of age by the Spacelabs instrument].

For a finer assessment, by repeated blood pressure (BP) measurements, of the cardiovascular risk associated with BP levels, new instruments have been developed which provide multiple reading during periods of activity. However, the lack of epidemiological studies makes it necessary to determine reference ambulatory BP levels by another method. Twelve-hour recordings were taken with the Spacelabs instrument in 130 volunteers (45% males) aged from 20 to 90 years during their various activities. Mean systolic and diastolic BP values +/- SD were calculated per age-groups of 10 years each. That this sample was representative of the general population was confirmed by the fact that BP fluctuations and variations according to age and sex in these 130 subjects were identical with those observed in the population of an entire town (Framingham). The concept of hypertension, as defined by ambulatory BP recordings, is discussed. This study provides, for the first time, reference ambulatory BP values according to age and sex, measured in normotensive subjects with the Spacelabs instrument. These values constitute a preliminary step indispensable to evaluate this technique in hypertensive patients.

Adult↗

PubMed1987

Converting enzyme inhibition and kidney function in normotensive diabetic patients with persistent microalbuminuria.

The effects of a long term reduction in blood pressure on the kidney function of normotensive diabetic patients who had persistent microalbuminuria (30-300 mg albumin/24 hours) were studied in two groups of 10 such patients before and during six months of treatment with either 20 mg enalapril or placebo daily. Treatments were assigned randomly in a double blind fashion. Before treatment both groups had similar clinical characteristics, weight, diet, total glycosylated haemoglobin, median albumin excretion rate (enalapril group 124 mg/24 h, placebo group 81 mg/24 h), and mean arterial pressure (enalapril group 100 (SD 8) mm Hg, placebo group 99 (6) mm Hg). During treatment weight, urinary urea excretion, and total glycosylated haemoglobin remained unchanged. The mean arterial pressure decreased in the enalapril group but not in the placebo group (enalapril group 90 (10) mm Hg, placebo group 98 (8) mm Hg). The median albumin excretion rate also fell in the enalapril group but not in the placebo group (enalapril group 37 mg/24 h, placebo group 183 mg/24 h.) The glomerular filtration rate rose in the enalapril group from 130 (23) ml/min/1.73 m2 to 141 (24) ml/min/1.73 m2, and total renal resistances and fractional albumin clearance decreased while fractional albumin clearance increased in the placebo group. These results show that in patients who have diabetes but not hypertension a reduction in blood pressure by inhibition of converting enzyme for six months can reduce persistent microalbuminuria, perhaps by decreasing the intraglomerular pressure.

Adult↗

PubMed1987

Treatment of mild to moderate hypertension with or without the converting enzyme inhibitor enalapril. Results of a six-month double-blind trial.

A group of 205 patients with mild to moderate essential uncomplicated hypertension was chosen from 3,183 hypertensive patients referred to a hypertension clinic for the first time, and was asked to participate in a six-month double-blind parallel trial. A single physician was in charge of all the patients. After a two-week single-blind placebo period, the patients were randomly assigned to regimens of either enalapril (20 mg per day) or placebo. Both groups were then followed up every two weeks, and increasing doses of hydrochlorothiazide (25 and 50 mg), oxprenolol (160 and 320 mg), and dihydralazine (50 and 100 mg) were added until the diastolic blood pressure was lower than 90 mm Hg. After a six-month follow-up, the enalapril group showed lower systolic and diastolic blood pressures than the control group (129/82 +/- 12/6 mg Hg versus 135/86 +/- 10/5 mm Hg; p less than 0.001). The number of daily tablets of active drugs was 2.7 +/- 1.8 in the enalapril group and 4.4 +/- 2.4 in the control group (p less than 0.01). The mean plasma potassium level was 4.16 +/- 0.4 mmol/liter in the enalapril group versus 3.92 +/- 0.4 mmol/liter in the control group (p less than 0.001), despite more frequent use of amiloride (p less than 0.001). This difference is explained by the lower dose of hydrochlorothiazide used in the enalapril group by comparison to the control group, and a lower excretion of urinary aldosterone in the enalapril group than in the control group (11.6 +/- 7.4 versus 19.8 +/- 11.8 micrograms per 24 hours, p less than 0.001). Drug withdrawal was necessary in eight patients in the enalapril group and in 16 patients in the control group (p less than 0.05). These results show that first-step treatment of mild to moderate uncomplicated essential hypertension with enalapril permits better blood pressure control than the standard treatment, requires fewer tablets to be taken daily, and involves a smaller risk of hypokalemia.

Adult↗

PubMed1987

Active immunization against renin in normotensive marmoset.

Primate renins (human and monkey) are very similar. We used pure human renin to immunize marmosets (Callithrix jacchus) and thereby produce a chronic blockade of the renin-angiotensinogen reaction. After a control period of 2 months, five male marmosets, on their usual sodium-poor diet, were immunized against pure human renin by three subcutaneous injections of 30 micrograms each, with complete and then incomplete Freund's adjuvant. Three marmosets were injected with adjuvant only and served as controls. Blood sampling and blood pressure measurements were performed weekly. After the third injection, the five marmosets immunized against renin developed a high titer of renin antibodies (50% binding of 125I-labeled human renin at a dilution of greater than or equal to 1:10,000). The antibodies inhibited the enzymatic activity of both marmoset and human renins. At the same time, systolic blood pressure decreased significantly from 125 +/- 13 mm Hg to 87 +/- 8 mm Hg (mean +/- SD; 1 mm Hg = 133 Pa). Plasma renin enzyme activity was undetectable in three animals. Plasma aldosterone decreased significantly. After 1-4 months with low blood pressure, a normal urinary output, and a normal plasma creatinine, the five marmosets became sick and died within one month. At autopsy an immunological renal disease, characterized by the presence of immunoglobulin and macrophage infiltration colocalized with renin, was found. Granulomatous formations, probably due to Freund's adjuvant, could be seen in the lungs and in the kidney. No immunoglobulin was detectable in extrarenal vessels or in other organs. These experiments demonstrate that, in this primate, a chronic blockade of the renin-angiotensin system can be achieved by active immunization against homologous renin, but this blockade is associated with the development of an autoimmune disease localized in the kidney.

Animals↗

PubMed1987

Evaluation of slow release nicardipine in essential hypertension by casual and ambulatory blood pressure measurements. Effects of acute versus chronic administration.

We conducted a randomized placebo-controlled double-blind study in 40 hypertensive subjects to assess the antihypertensive effect of a new galenic form of nicardipine administered at a dosage of 50 mg twice daily for 3 weeks. Regardless of whether blood pressure was measured by standard mercury sphygmomanometer, non-ambulatory automatic oscillometry or a Remler ambulatory blood pressure recorder, it dropped by a significantly larger amount in the nicardipine group than in the placebo group. In the control group, a placebo effect was observed with the ambulatory diastolic blood pressure recording, whereas it was not observed with hospital blood pressure measurements, especially when using the serial measurements performed for 30 min by an automatic recorder. The fall in blood pressure measured with the Remler recorder was correlated with the fall measured 10-20 min during one acute intravenous nicardipine perfusion before the trial, although the correlation coefficients do not suggest clinically relevant predictability of nicardipine efficacy at the individual level. The present findings support the need for controlled double-blind trials with careful office blood pressure measurements.

Administration, Sublingual↗

PubMed1987

Clinical and biochemical effects of the renin inhibitor H142 in humans.

The inhibitor of human renin, H142, was studied in nine male volunteers. On three occasions, in random order, volunteers were infused with 5% dextrose, or with H142 at 1.0 or 2.5 mg/kg/h, for 30 min while supine and thereafter with dextrose for 1.5 h. There was a marked reduction in plasma active renin concentration as assayed by an enzyme-kinetic method, with parallel falls in the circulating concentrations of angiotensins (ANG) I and II, all of which rebounded transiently to values above basal after H142 infusion was stopped. In contrast, total renin concentration as measured by radioimmunoassay rose while ANG I and II fell, subsiding after H142 was discontinued. There was a slight but significant increase in plasma noradrenaline as renin became inhibited: plasma adrenaline was unchanged. H142 produced a slight fall in systolic blood pressure (SBP) and a clearer, highly significant, dose-related fall in diastolic blood pressure (DBP). There was modest but significant increase in the heart rate. These studies confirm H142 as an effective inhibitor of human renin in vivo.

Adult↗

PubMed1987

Measurement of active renin by the 4G1 anti-human renin monoclonal antibody.

Three monoclonal human renin antibodies have been selected to settle two immunoradiometric assays of human plasma renin (IRMA). The first pair of antibodies 3E8-4G1 recognizes exclusively active renin (AR), as demonstrated by the lack of increase either of the number of AR molecules or the renin enzymatic activity, when plasma is set free of inactive renin (IR) by immunoaffinity chromatography with human renin prosegment monoclonal antibody. The second pair of monoclonal antibodies 4E1-3E8 gives results which are very significantly correlated to those obtained with the 3E8-4G1 pair after trypsin activation. The standardization of renin measurements with use of monoclonal antibodies, and the standardization of renin will allow the exchange of comparable informations between the various laboratories involved in the investigation of the renin-angiotensin system in humans.

Antibodies, Monoclonal↗

PubMed1987

Efficacy and influence on quality of life of enalapril as a first step treatment of hypertension.

205 patients with mild to moderate uncomplicated hypertension participated in a six-month double-blind parallel study performed in a unique center. After a two-week single-blind placebo period, the patients were randomly allocated to receive either Enalapril 20 mg once-a-day or placebo as the first step treatment. They were then followed-up every two weeks and successive doses of hydrochlorothiazide, oxprenolol, and dihydralazine were added until the diastolic pressure was lower than 90 mmHg. After six months, the systolic and diastolic blood pressures were lower in the Enalapril than in the control group (129/82 +/- 12/6 mmHg versus 136/86 +/- 10/5 mmHg; p less than 0.001). Drug withdrawal was necessary for 8 patients in the Enalapril group and for 16 patients in the control group (p less than 0.05). The number of daily tablets was 2.7 +/- 1.8 in the Enalapril group and 4.4 +/- 2.4 in the control group (p less than 0.01). Therefore, a stepped-care program based on Enalapril appears significantly more effective than a stepped-care program based on a diuretic.

Adult↗

PubMed1987

[Definition and consequences of blocking the renin-angiotensin system by converting enzyme inhibition].

46 patients (39 males), mean age 51 years (range 33-66), were randomly allocated to two different groups of treatment if their diastolic blood pressure was superior to 90 mmHg after a one-month treatment by 20 mg of enalapril. In the first group (ENA), 23 patients were given higher dosages of enalapril (40 and, if necessary 60 mg once-a-day). In the second group (HCTZ) 23 patients were given enalapril 20 mg and hydrochlorothiazide 25 and, if necessary, 50 mg once-a-day. Dosages were eventually increased after 2 weeks and evaluation of the results was performed after 4 weeks on treatment. Blood pressure was monitored in the supine position, at 3 minutes interval for thirty minutes, by an automatic device based on oscillometric method. Two successive measurements with a standard sphygmomanometer were performed by the physician at the end of the recording. No patient withdrew from the study nor was lost to follow-up. At the end of the study, 14 patients in the ENA group were receiving enalapril 60 mg once-a-day and 8 patients in the HCTZ group were receiving 50 mg of hydrochlorothiazide. Blood pressure was significantly lower in teh HCTZ group with the automatic device (130 +/- 9/80 +/- 8 vs 141 +/- 5/86 +/- 8 mmHg, p less than 0.01/p less than 0.05) and with the sphygmomanometer (134 +/- 10/89 +/- 6 vs 149 +/- 16/94 +/- 5 mmHg, p less than 0.001/p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Effect of vasodilatators on the structure of the aorta in normotensive ageing rats.

The effects of hypertension and its treatment on the function and structure of arteries have been extensively studied, but no data are yet available on the effect of hypotensive drugs on the large arteries in normotensive rats. Two groups of 11-month-old normotensive breeder male rats were treated for 5 months, one with an angiotensin converting enzyme (ACE) inhibitor (MK-421, 2 mg/kg per day; n = 10) and the other with dihydralazine (15 mg/kg per day; n = 8). A group of 14 rats served as controls. Blood pressure was recorded every 14 days by the tail-cuff method. At the end of the treatment period (5 months), the rats were killed under anaesthesia and the descending thoracic aorta was removed and fixed. The different components of the aorta were assessed by automated morphometric image analysis after specific coloration of elastin (orceine), collagen (sirius red) and nuclei (haematoxylin after periodic acid oxidation. Both the ACE inhibitor and dihydralazine caused similar decreases in systolic blood pressure (SBP) compared with controls. This hypotensive effect was associated with a reduction in medial thickness, from 120 +/- 15 microns in controls to 104 +/- 9 microns in ACE inhibitor-treated and 103 +/- 10 microns in dihydralazine-treated normotensive rats. Elastin density significantly increased in the two treatment groups but the greatest increase was in the dihydralazine-treated group (P less than 0.001). Elastin fibre thickness increased significantly in the dihydralazine-treated group only. Collagen density was not significantly modified by either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1987

[Comparison of the effect of captopril and minoxidil on left ventricular mass. Results of a 6-month comparative double-blind test].

A randomised double blind study was performed in order to compare the cardiac effects of captopril and minoxidil in a subset of patients with severe primitive hypertension, uncontrolled (diastolic BP greater than 100 mmHg) by Metroprolol 200 mg/d and Furosemide 80 mg/d. 25 male pts completed the six month study, 33 pts having been excluded before randomisation (22 inadequate echoes) and 20 after randomisation (7 ambiguities on wall measurement). Average captopril dosage was 265 mg/d (150-300 mg), average minoxidil dosage was 19.6 mg/d (7.5-30 mg), dosages of Furosemide, Spironolactone and Metroprolol were similar in the two groups. Blood pressure decreased dramatically with both regimens (208/130 to 148/96 with captopril, 194/115 to 154/100 with minoxidil). Sokolow index was at the upper range of normal and decreased with both drugs. Cardiothoracic ratio decreased only with captopril. Echocardiograms were performed and read blindly at the end of the study. LV mass was measured according to Devereux, method. All patients had severe LVH. After 6 months posterior wall thickness decreased from 14.8 to 13.8 mm with captopril, remained stable from 14.1 to 14.9 mm with minoxidil, septal thickness decreased from 17.2 to 15.7 mm with captopril and remained stable (14.8 to 15.2 mm) with minoxidil. LV mass and mass index respectively decreased from 456 g and 232 g/m2 to 372 g and 190 g/m2 with captopril, and remained unchanged from 413 g and 215 g/m2 to 420 g and 218 g/m2 with minoxidil. Fractional shortening remained normal in both groups. Intra patients reproducibility was suboptimal because of difficulties in precise delineation of the endocardium in the severely hypertrophied ventricles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Renal damage induced in the clipped kidney of one-clip, two-kidney hypertensive rats during normalization of blood pressure by converting enzyme inhibition.

Explore the source record for details and available documents.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1987

From the renin gene to renin inhibitors.

Explore the source record for details and available documents.

Angiotensinogen↗