High plasma levels of endothelin-1 in untreated Addison's disease.

The aim of this study has been to investigate the plasma endothelin-1 (ET-1) levels in adult patients with proven Addison's disease (AD). Plasma ET-1 levels were measured in 29 subjects (17 males and 12 females, aged between 20 and 54 years): 15 of them were patients with AD and 14 were sex- and age-matched normal subjects, used as a control group. All patients with AD have been studied under basal conditions and nine of them also after 2 weeks on oral corticosteroid therapy (individual cortisol dosage ranging from 25 to 37.5 mg/day and 0.1 mg/day 9 alpha-fluorohydrocortisone). Extracted plasma ET-1 was determined by a specific radioimmunoassay using rabbit endothelin antisera. Mean ET-1 values in the patients with AD were three times higher than in normal subjects (21.09 +/- 4.38 pg/ml vs 6.72 +/- 1.74 pg/ml; p < 0.0001). Plasma ET-1 levels assayed in the patients with AD after 2 weeks of corticosteroid therapy were significantly decreased (14.47 +/- 3.7 pg/ml vs 22.8 +/- 5.2 pg/ml; -37%; p < 0.001) compared to values in untreated patients. However, the plasma ET-1 values obtained following corticosteroid therapy were still significantly higher (p < 0.001) than those detected in the control subjects. These results clearly indicate that patients with untreated AD have increased circulating ET-1 levels that may be reduced by short-term corticosteroid therapy.

Increased plasma levels of endothelin-1 in patients with hyperthyroidism.

Plasma concentrations of endothelin-1 (ET-1) were measured in 25 hyperthyroid subjects, 15 hypothyroid subjects, and 21 age-matched normal controls. In hyperthyroid patients, plasma concentrations of ET-1 were significantly higher than in the control group (P < .0001) and in hypothyroid patients (P < .0001). In contrast, no differences were found between hypothyroid patients and controls. Plasma levels of ET-1 were similarly elevated as in patients with Graves' disease and those with toxic adenoma. No correlations were found between plasma ET-1 levels, thyroid hormones, and thyrotropin (TSH) in hyperthyroid, hypothyroid, and euthyroid groups. The results of our study clearly indicate that in hyperthyroidism, circulating levels of ET-1 are strongly increased, although the pathogenesis of the increase is unclear.

Plasma endothelin-1 levels in normotensive and borderline hypertensive subjects during a standard cold pressor test.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide derived from endothelium. The presence of ET-1 in human vascular endothelium and in the plasma suggests that it may play a role in the regulation of vascular tone and blood pressure (BP) in humans. The aim of this study was to evaluate the behaviour of plasma ET-1 in 10 normotensives (average 36.3 +/- 14.8 years) and 10 borderline hypertensives (average 42.0 +/- 11.7 years) before, during and after a standard cold pressor test. We also evaluated the behaviour of heart rate and BP at the same time. Our results demonstrated that the baseline (-10 and 0 min) plasma ET-1 values were identical for the two groups (8.6 +/- 5.8 and 8 +/- 4.7 pg/ml in normotensives; 7.8 +/- 2.7 and 7 +/- 2.4 pg/ml in borderline hypertensives). A statistically significant increment was verified 10 min after exposure to cold in the borderline hypertensive group (12.1 +/- 5.1 pg/ml) compared with the normotensives group (6.8 +/- 4.5 pg/ml; P < 0.05). In conclusion, our study demonstrated that after 10 min of cold pressor stimulus an increase of circulating ET-1 levels was seen in borderline hypertensives.

High plasma endothelin-1 levels in hypertensive patients with low-renin essential hypertension.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide derived from endothelial cells and may be important in the control of systemic blood pressure (BP) and local blood flow. Immunoreactive ET-1 plasma levels may be normal or elevated in human arterial hypertension, although the exact pathophysiological role of ET-1 remains to be established. The aim of our study was to determine the relationship between the components of the renin-angiotensin-aldosterone system and plasma ET-1 levels in patients with low, normal or high-renin essential hypertension. The study groups included 13 patients with low-renin essential hypertension (average age 43.5 +/- 16.2 years), 16 patients with normal-renin essential hypertension (46.5 +/- 13.4 years), 11 patients with high-renin essential hypertension (40.7 +/- 13.8 years) and 12 healthy subjects (43.1 +/- 11.4 years). Our results demonstrated that the mean ET-1 values of all patients with essential hypertension were 10.4 +/- 3.4 pg/ml; there was not a statistical correlation between plasma renin activity (PRA) and the ET-1 levels of hypertensives; instead there was a statistically significant correlation between plasma ET-1 and plasma aldosterone (PA) (r = 0.393; P < 0.026). In particular mean plasma ET-1 values in patients with low-renin essential hypertension (12.6 +/- 2.1 pg/ml) were significantly higher (ANOVA = 0.000, P < 0.05) than those of normotensive subjects (7.7 +/- 1.7 pg/ml), patients with normal-renin essential hypertension (8.5 +/- 2.8 pg/ml), and patients with high-renin essential hypertension (9.9 +/- 3.8 pg/ml), respectively. There was a statistical correlation between PA and ET-1 levels in patients with low-renin essential hypertension (r = 0.619, P < 0.024). Our study demonstrated that there was an increase of circulating ET-1 levels in patients with low-renin essential hypertension and ET-1 plasma levels correlated with PA. The results suggest that ET-1 may play an important role in this particular form of human essential hypertension.

Effects of caloric restriction and exercise on B-endorphin, ACTH and cortisol circulating levels in obesity.

B-Endorphin (B-Ep), ACTH and cortisol circulating levels, before and after a two months therapy with a hypocaloric diet and an increase in physical exercise, were measured by RIA in 17 obese female subjects. After therapy, the body weight excess fell from 56.6 +/- 22.2% to 38.6 +/- 22.1% (p less than 0.01). Plasma levels of B-Ep decreased from 18.3 +/- 12.5 fmol/ml to 6.4 +/- 3.5 fmol/ml (p less than 0.01); those of ACTH from 46.8 +/- 22.8 pg/ml to 31.2 +/- 11.6 pg/ml (p less than 0.01); and those of cortisol from 15.9 +/- 4.6 micrograms% to 10.3 +/- 2.5 micrograms% (p less than 0.01). The reduction of the elevated plasma B-Ep levels found in obese subjects is related principally to the diet therapy. Thus, as shown in experimental animals, excessive feeding results in an increased hypothalamic-pituitary secretion of B-Ep.

Hyperendorphinemia in obesity is not related to the affective state.

In seventy-two patients affected by hyperphagic obesity and forty age-matched, normal weight volunteers we performed a psychological assessment, through various mental tests, and evaluated the beta-endorphin (B-Ep), ACTH and cortisol circulating levels, in basal condition and following an overnight short dexamethasone suppression test (DST). The hormones were measured by radioimmunoassay either directly in the serum (cortisol) and the plasma (ACTH), or after affinity gel column chromatography (B-Ep). In obese subjects B-Ep levels in basal conditions were four times greater than in normal weight controls and showed significantly less reduction after DST. ACTH and cortisol levels, in contrast, were in the normal range and were suppressed following dexamethasone as was also true in the control group. Psychological evaluation on M.M.P.I. (Minnesota Multiphasic Personality Inventory) revealed a trend toward hypochondria, depression, hysterias, psychoasthenia and schizophrenia. However, no significant correlation has been found between M.M.P.I. clinical scale scores and circulating levels of B-Ep and cortisol either in basal conditions or after DST. In conclusion, these data do not support the hypothesis that abnormalities of the hypothalamus-pituitary-adrenal axis in hyperphagic obesity are related to affective disorders.

Hyperendorphinemia in obesity and relationships to affective state.

Eight obese patients (exceeding ideal body weight by 50% or more) with no endocrinological or metabolic disorders and 8 healthy, age-matched, normal-weight volunteers were submitted to an overnight short dexamethasone (DXM) suppression test and to a psychological assessment through various psychometric scales. Plasma B-Endorphin (B-EP), B-Lipotropin (B-LPH), ACTH and cortisol concentrations were evaluated in basal conditions, as well as 9 and 17 hours after late night administration of 1 mg DXM in both groups. All hormones were measured by radioimmunoassay, either directly in the plasma (ACTH and cortisol) or after silicic acid extraction and Sephadex G-75 column chromatography (B-LPH and B-EP). In obese patients, plasma B-EP levels in basal conditions were three times higher than in normal weight controls and remained unaltered by DXM suppression. ACTH and B-LPH, in contrast, were within the normal range and were significantly reduced by DXM. In 3 of the 8 patients, plasma cortisol concentrations at 17 hours post-DXM were greater than 50 ng/ml indicating an early escape from the suppression. Psychometric evaluations revealed a prevalence of depressive personality in obese patients. These data indicate an hypersecretion of B-EP in obese patients, which is only partially dependent on hypothalamic control.

Effect of ageing on circadian rhythms of plasma renin and aldosterone in mesor-hypertensive women.

This study investigated the changes in circadian rhythms of plasma renin activity (PRA) and plasma aldosterone (PA) which occur in essential mesor-hypertensive women, increasing in age. Systemic blood samples were taken throughout a 12 h period from both mesor-hypertensive women and clinically healthy women (control). The women in each group were either post-menopausal or had normal menstrual cycles. A cosinor method of temporal series was the analysis employed to compute the properties of PRA and PA circadian rhythms. The clearest effect of ageing, recorded in essential mesor-hypertensive women, is a decrease in circadian mesor of PRA cycle (P = 0.002). The age-related changes in clinically healthy women appear to be more extensive and involve a decrease for both mesor (P less than 0.001) and amplitude (P = 0.007) of PRA circadian rhythm. These disparities are convincing evidence for a non-physiological decline of the RAAS rhythmic function in the aged essential mesor-hypertensive women. The lack of an age-associated decrease in circadian PRA amplitude merits and pathophysiological and clinical investigation because it is a possible risk factor for post-menopausal, essential mesor-hypertensive women.

Ageing and circadian rhythm of plasma renin and aldosterone.

Five men and 8 women, 60-69 yr of age, and 4 men and 5 women, 17-37 yr of age, volunteered for this exploration of possible age-related changes in circadian-rhythm (CR) characteristics of radioimmunoassayable plasma renin (PRA) and aldosterone (PA). Blood was drawn at 06.00, 08.00, 12.00, 18.00, 20.00 and 24.00 from recumbent subjects on a habitual sodium intake of 120-140 mEq/24 h. Time-qualified data of PRA and PA, fitted by a 24-h cosine curve, were summarized by a population mean-cosinor method. Circadian characteristics were compared by a multivariate analysis using Hotelling's t2 test. Rhythmometry reveals in the elderly women a lower mesor (P less than 0.001) and amplitude (P = 0.036) of the CR in PRA and a higher mesor and amplitude (P = 0.021 and P = 0.020, respectively) of the PA-CR. The PRA acrophase is delayed (P less than 0.001) in the elderly women (04.40 vs. 08.04) while the timing of the PA acrophase is similar in the age groups of women compared (05.52 vs. 05.20). These differences found in women were not observed in the smaller groups of men. The seventh decade of life may be characterized by an internal circadian desynchronization between the major components of the renin-angiotensin-aldosterone system. A sex-dependent amplification of the extent of circadian variation in aldosterone may precede a decrease in the circadian amplitude occurring during the eighth decade of life, as a sign of the adrenopause in women.

Temporal correlation of some endocrine circadian rhythms in elderly subjects.

The aim of this chronobiological study was to investigate temporal correlations in the circadian patterns of 6 hormones, namely somatotrophic hormone (STH), prolactin (PRL), cortisol (F), aldosterone (ALD), insulin (IRI) and C-peptide (CP), assayed in systemic blood serum drawn at 07:00, 10:00, 13:00, 16:00, 19:00 and 22:00 h from an antecubital vein in 19 young subjects (aged 20-29 yr, comprising 10 males and 9 females; and 20 elderly subjects (aged 70-81 yr, comprising 10 males and 10 females). All subjects were sampled on a normal dietary sodium intake (120-140 mEq/24h) while following a social routine of diurnal activity (07:00-23:00) and nocturnal rest (23:00-07:00). Time-qualified data were analyzed by lead-lag correlation and by cosinor analysis. According to the lead-lag correlation findings, it would appear that the correlation which exists between several time-qualified series in young subjects is no longer present in elderly subjects. The circadian rhythms which were found to have lost their temporal correlations with advancing age were those between STH and IRI, STH and ALD, PRL and IRI, PRL and CP, and ALD and CP. It should be noted that the correlation between hormonal rhythms breaks down mainly on account of a peculiar age-related change in the magnitude of the circadian fluctuation. This chronological decline in amplitude led to the conclusion that the senescence of endocrine rhythmic functions is a biological phenomenon characterized by altered circadian variability.

A chronobiological approach to circulating levels of renin, angiotensin-converting enzyme, aldosterone, ACTH, and cortisol in Addison's disease.

This study deals with a chronobiological approach to the circadian rhythm of the renin-angiotensin-aldosterone system (RAAS) and the ACTH-cortisol axis (ACA) in patients with Addison's disease (PAD). The aim is to explore the mechanism(s) for which the circadian rhythmicity of the RAAS and ACA takes place. The study has shown that both the RAAS and ACA are devoid of a circadian rhythm in PAD. The lack of rhythmicity for renin and ACTH provides indirect evidence that their rhythmic secretion is in some way related to the circadian oscillation of aldosterone and cortisol. This implies a new concept: a positive feedback may be included among the mechanisms which chronoregulate the RAAS and ACA.

Effects of a mild and prolonged restriction in sodium or food intake on the circadian rhythm of aldosterone and related variables.

The effect of a mild reduction in dietary sodium intake (-30 mEq/24 hr) and body weight (-2 kg/2 months) on circadian rhythms of urinary aldosterone (UA), sodium (UNa), potassium (UK), creatinine (UC) and volume (UV) have been investigated in nine clinically healthy subjects. The mild reduction in dietary sodium is associated with: (1) a decrease in the 24-hr excretion rate of UNa, UK and UV, and an increased mesor of UA and UC; (2) a lowered extent of the circadian variation for UNa, UK, UV and a greater amplitude for UA and UC (3) a later crest in the temporal phase for UK, UA, UC, an earlier phasic wave for UNa. The mild reduction in calorie intake resulting in a body weight loss is associated with a more pronounced decrease in the 24-hr excretion rate of UNa and UK, and in the extent of circadian fluctuation for UNa. Peculiar events are: (1) the decreased 24-hr excretion rate for UA, and the increased mesor for UV; (2) the extent variability increased for UV, decreased for UC. Such effect may have a practical resonance for heuristic physiology since the role of dietary sodium and food intake has been better clarified. Dietary sodium and food can be regarded as 'chronomodulatory agents' for the adrenal cortex since their adrenotropic influence is extended to the tonic as well as phasic secretion of aldosterone.

Circadian rhythms of plasma renin activity and aldosterone: changes related to age, sex, recumbency and sodium restriction. Chronobiologic specification for reference values.

Plasma renin activity (PRA) and aldosterone (PA) levels are characterized by a circadian rhythmicity (CR). The present study revealed that this rhythmicity is influenced by several factors including posture, sodium intake and age. Time-qualified PRA and PA reference intervals can reduce the incidence of false positives and false negatives in a diagnostic work-up. The circadian rhythmicity of PRA and PA have been quantified in relation to posture, sodium intake and age. The cosinor procedure has been applied to quantify the properties of the circadian rhythmicity under these conditions. Chronograms and circadian parameters can be used to optimize the use of PRA and PA measurements in clinical practice. The chronobiological specification of reference values for PRA and PA is of valuable importance since the assessment of PRA and PA circadian rhythmicity has a diagnostic interest for a certain type of clinical disorder. It should be noted that several studies have described circannual variations for renin and aldosterone. The next step in the optimation of laboratory time-qualified reference values is the assessment of changes induced by the deterministic factors on a circannual domain.

[The role of the endogenous opioid system in the pathogenesis of polycystic ovary syndrome: the altered neuroendocrine regulation of GnRH-LH is corrected after clomiphene therapy]. / Il ruolo del sistema oppioide endogeno nella patogenesi della sindrome dell'ovaio policistico: l'alterata regolazione neuroendocrina di GnRH-LH si corregge dopo terapia con clomifene.

To investigate whether inappropriate LH secretion in Polycystic Ovary Syndrome (PCO) was related to a reduction of inhibitory opioid control on the GnRH-LH system, 23 women affected by PCO (12 obese, BMI: 37.1 +/- 3.9 and 11 non obese, BMI: 21.5 + 2.4) and 19 fertile women (10 obese, BMI: 38.8 + 1.8 and 9 non obese, BMI: 20.1 + 1.5) were studied. Plasma levels of Beta-Endorphin (B-Ep) in basal condition and LH and FSH serum levels following acute administration of naloxone (0.1 mg/kg e.v.) were evaluated in the PCO and control groups. Moreover, in order to investigate whether the neuroendocrine abnormalities in PCO are a primary hypothalamic defect or secondary to an inappropriate feedback of gonadal steroids, the LH response following Naloxone administration was evaluated again after two months of clomiphene therapy (50 mg p.os ones a day for 5 days). The women affected by PCO had increased LH/FSH ratio, testosterone levels (P < 0.001, P < 0.01) and significantly decreased T/E2 ratio, SHBG levels compared to the normal women (P < 0.01, P < 0.001). B-Ep plasma levels in PCOs OB and PCOs nOB (6.13 + 1.2 Pmol/L, 4.8 + 0.4 Pmol/L) were similar to those observed in obese and non obese control women (7.2 + 2.5 Pmol/L, 4.2 + 1.3 Pmol/L), respectively. In the PCO and control groups naloxone induced a significant increase of FSH and LH levels. Thus the area under the curve of LH and FSH was significant higher after naloxone, than following saline infusion both in PCO (P < 0.01, P < 0.05) and controls (P < 0.001, P < 0.001). However, in PCO the post naloxone FSH increase was similar to that found in fertile women, while the LH increase post naloxone was lower than that observed in controls (50 + 32.4% vs 101.6 + 36.7%; P < 0.01). Particularly in PCO with LH/FSH ratio equal or higher than 3, no significant variation of LH levels was found after naloxone. Moreover the LH increase post naloxone was similar in PCO OB (46 + 19.8%) and in PCO nOB (49.9 + 13.1%), correlated negatively with LH basal levels (P < 0.02), LH/FSH (P < 0.005), E1/E2 (P < 0.005) and was independent of T/E2, BMI and duration of the disease. Following clomiphene treatment, the LH response after naloxone was significantly higher than that observed before treatment (from 9.4 + 4.2 mUI/ml to 16.5 + 3.9 mUI/ml, P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

[Insulin resistance in obese and non-obese patients with polycystic ovary syndrome. Possible role in the pathogenesis of the disease]. / L'insulinoresistenza nelle pazienti con sindrome dell'ovaio policistico (PCOs) obese e non obese. Possibile ruolo nella patogenesi della malattia.

The pathogenesis of Polycystic Ovary Syndrome (PCOs) is not well known till now. Previous reports indicated an hyperinsulinemia and insulin resistance in obese and non obese PCOs. However the role of hyperinsulinemia in PCOs pathogenesis is not completely understood. In this study we evaluated the glycemic and insulinemic response to OGTT in 21 women suffering from PCOs (13 obese and 8 normal weight) and in 16 fertile women as a control group (8 obese and 8 normal weight). All tested women showed normal glycemia before and after OGTT. Basal insulinemia in PCOs was similar to that observed in control group. Mean insulinemic levels following OGTT in obese control group and in PCOs were significantly higher than those observed in normal women (p < 0.05). Insulin area under curve (AUC) following OGTT in non obese PCOs was significantly higher than that observed in non obese control women (72442.13 +/- 18668.9 mUI/ml/h versus 53710.8 +/- 83365 mUI/ml/h; p = 0.02), but lower than that observed in obese PCOs (192793 +/- 49421; p < 0.001). In obese PCOs insulin AUC was significantly higher than that observed in obese control group (138836.8 +/- 28800.9; p = 0.012). Insulin AUC was positively related to BMI in control group (p < 0.001) but not in PCOs. In PCOs group insulin AUC was positively related to hirsutism degree (p = 0.032) and circulatory levels of T (p = 0.044), LH (p < 0.001) and E1 (p = 0.026).(ABSTRACT TRUNCATED AT 250 WORDS)

Cushing's disease and prolonged spontaneous remission. Clinical case.

We describe a case of prolonged spontaneous remission of Cushing's disease lasting since 1986 and documented both clinically and biochemically. This case confirms previous sporadic observations based mainly on clinical findings and indicates that spontaneous remission of Cushing's disease, although rare, may exist. The Authors outline that in some cases of Cushing's disease it could be convenient to adopt a conservative policy with frequent outpatient reviews in order to observe the natural course of the disease, particularly when the clinical findings are mild and the original lesion is not recognized with the available technology.

[Tubercular Addison's disease with high titers of microsomal thyroid antibodies and reduced thyroid function reserve]. / Morbo di Addison tubercolare con elevato titolo di anticorpi antimicrosomiali tiroidei e ridotta riserva funzionale della tiroide.

This case reports deals with a male patient, white, aged 51, bricklayer, tobacco smoker. At 43 years old a tubercular epididimite was surgically treated with orchiectomy. Recently, the reports marked weakness, weight loss, headache, vertigo, hypotension. On admittance to the hospital, hyperpigmentation was also present. Previous therapy (cortisone acetate 40 mg/die), was suspended, clinical investigations showed impaired adrenal and thyroidal functions; antimicrosomal antibodies were also present. Therefore therapy with cortisone acetate (25 mg x 2/die, 9-alpha-fluorohydrocortisone 0.1 mg/die and L-thyroxine 100 mcg/die) was instituted with marked improvement of the patient's conditions. This case reports highlights the importance of proceeding with complete investigations on the system, even when dealing with a tubercular Addison's disease.

[Serum activity of angiotensin-converting enzyme and osteocalcin levels in hyperthyroidism]. / L'attività sierica dell'enzima di conversione dell'angiotensina ed i livelli di osteocalcina nell'ipertiroidismo.

This study was carried out in order to investigate serum changes of osteocalcin (BGP) and angiotensin converting enzyme (SACE) activity in a group of patients with hyperthyroidism. We studied 20 hyperthyroid patients (F 14, M 6; age mean 37.5 +/- 16.8 years) and 13 control subjects (F 11, M 2; age mean 40.3 +/- 7.5 years). In both patients and controls we measured: FT3, FT4, T3, T4, TSH, BGP, SACE. Finally, in patients with hyperthyroidism a TRH test and functional investigations were also performed. We observed that mean SACE levels were significantly increased in hyperthyroid patients (32.06 +/- 10.3 nmol/ml/min) in respect to control subjects (14.66 +/- 3.88 nmol/ml/min) (p = 2.02 E-6). Similarly serum BGP levels were significantly increased in hyperthyroid patients (5.94 +/- 2.55 ng/ml) than in control subjects (2.89 +/- 1.58 ng/ml) (p = 5.66 E-4). There was a significant linear correlation between SACE and T4 levels (r = 0.48; p < 0.05), between serum BGP and T4 (r = 0.50; p < 0.02) and furthermore between SACE and BGP (r = 0.57; p < 0.01). In conclusion both serum BGP and SACE levels are increased in patients with hyperthyroidism and are directly correlated between than and with indexes of thyroid function; therefore, they may be regarded as peripheral indexes of hyperthyroidism.

The effect of enalapril on nephrotic proteinuria and determination of serum angiotensin-converting enzyme before and after treatment.

In order to evaluate the effect of an ACE-inhibitor (enalapril) on nephrotic proteinuria in patients with primitive nephropathies, to determine the SACE before and after treatment and to compare the variation of SACE levels with the variations of proteinuria, seventeen patients were studied (5 F, 12 M) aged between 10 and 68 years. All patients were evaluated in basal conditions for creatinine clearance, protidaemia, proteinuria, SACE and serum electrolytes. All but one patient had a renal biopsy. After basal evaluation nine patients received enalapril, 10 mg/die, for two weeks. After one week SACE levels were re-evaluated, while the proteinuria was re-evaluated several times during the two weeks of treatment. The results obtained suggest (1) SACE levels are significantly higher in patients with nephrotic syndrome than in normal patients (21.14 +/- 8.37 nmol/ml/min; N.V.:15.60 +/- 4.73; M +/- s.d.; p less than 0.01); (2) proteinuria is unresponsive to the ACE-inhibitor action (varied from 8.00 +/- 2.70 g/24 h to 7.74 +/- 3.19 g/24 h, p = NS); (3) no correlation exists between the reduction of SACE levels and variations of proteinuria.

Amlodipine in ambulatory hypertensive patients: humoral and haemodynamic effects.

In order to evaluate the mid-term effects of amlodipine, a 1,4-dihydropyridine calcium antagonist, as well as its effects on the renin-angiotensin-aldosterone system (RAAS), on water and electrolyte balance, on urinary excretion of albumin (UAE) and on lipid metabolism, thirteen hypertensive patients (2 M, 11 F, mean age 54 years) were studied in the course of 24 weeks of therapy with amlodipine at 5-10 mg/day. Pre-therapy and periodically during therapy, the systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were recorded in the sitting orthostatic positions (2 measurements). Laboratory tests were performed at times O and at 24 wks with the patients fasting for at least 12 h in the recumbent position. The tests included: plasma renin activity (PRA), plasma aldosterone (PA), serum angiotensin converting enzyme (SACE), blood urea nitrogen (BUN), blood creatinine, plasma electrolytes (Na, K, Cl), triglycerides, total cholesterol (TC) and HDL-cholesterol (HDLC), along with 24-h urine samples (with sterile urine) to determine UAE. The results of this study demonstrate that SBP, DBP and HR were significantly reduced during the 24 wks of therapy. The water and electrolyte and renal function were not modified. After treatment the levels of TC were significantly reduced. No change was observed in the RAAS, while the mean levels of UAE were reduced though not significantly. In conclusion, amlodipine was shown to be effective for the therapy of hypertension; it does not cause reflex tachycardia even in mid-term therapy and was effective in reducing TC levels.