D. Scavo

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.

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.

Circulating levels of adrenomedullin in patients with Addison's disease before and after corticosteroid treatment

A novel hypotensive peptide, adrenomedullin (AM), had recently been isolated, purifed and its encoding gene sequenced from a human phaeochromocytoma. In humans AM circulates in physiological levels and possesses a distinct vasodilatatory activity. The purpose of this study was to examine the behaviour of AM levels in primary adrenal failure.

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.

Circadian rhythms of plasma renin, aldosterone and cortisol on habitual and low dietary sodium intake.

To examine the effects of reducing sodium intake upon the renin-angiotensin-aldosterone system (RAAS), 5 healthy men and 5 healthy women, 17-37 years old, living under standardized conditions, were sampled around the clock, once on habitual and once on restricted sodium intake. Plasma renin activity (PRA), aldosterone (PA) and cortisol (PC) were determined by radioimmunoassay. All three variables were found to exhibit a statistically significant circadian rhythm, both on habitual and restricted salt intake. After salt restriction, an increase in midline-estimating statistic of rhythm (mesor) of PRA and PA, but not of PC, was observed. The acrophase (an estimate of the time of high values) for PC lagged behind that for PRA and PA. This difference in acrophase was of specially high statistical significance when subjects were on a sodium-restricted diet. These results demonstrate the importance of inferential statistical so-called rhythmometric methods: parameters such as the acrophase can also be used for the assessment of novel effects and for a quantification in time. The derivation of confidence intervals for each rhythm parameter allows one to verify that a given variable exhibits values bracketing an average not only between a higher and a lower, but also between an earlier and a later limit. Changes that may involve only the acrophase, such as a lead or lag, as here noted, are then detected and are of factual as well as methodological interest.

Plasma Endothelin-1 Levels in Patients with Aldosterone-Producing Adenoma and Pheochromocytoma

The aim of the study was to evaluate possible changes of plasma endothelin-1 levels (ET-1) in patients with hypertension secondary to primary aldosteronism and pheochromocytoma. We enrolled in the study: 12 patients affected by aldosterone-producing adenoma (5 M and 7 W; mean age 42.1 +/- 17.2 years); 8 patients with pheochromocytoma (5 M, 3 W; mean age 36.2 +/- 17.1 years); 15 patients with essential hypertension (9 M, 6 W; mean age 48.5 +/- 10 years). We also enrolled a normal control group (8 M, 12 W; mean age 34.2 +/- 11 years). The mean plasma ET-1 concentrations in patients with pheochromocytoma were significantly higher (23.9 +/- 5.2 pg/ml) than those in normal subjects (7.3 +/- 1.9 pg/ml), in patients with primary aldosteronism (12.1 +/- 3.8 pg/ml) and in patients with essential hypertension (9.2 +/- 3 pg/ml); p < 0.001, respectively. The present investigation demonstrates that in human adrenal hypertension patients with pheochromocytoma have increased circulating ET-1 levels respect to patients with aldosterone-producing adenoma.

Effects of Haemodialysis Session on Plasma Beta-Endorphin, ACTH and Cortisol in Patients with End-Stage Renal Disease

The effect of a regular haemodialysis session on the plasma concentrations of beta-endorphin, ACTH and cortisol was investigated in 14 patients with end-stage renal disease and 20 healthy controls. Blood for analysis of beta-endorphin, ACTH and cortisol was sampled before and immediately after haemodialysis. In four patients the dialysate was studied for presence of these hormones, but showed no specific activity. The predialysis beta-endorphin, ACTH and cortisol levels did not differ significantly from the control values. The postdialysis levels were significantly higher than the predialysis. Significant linear correlation was found between plasma ACTH and beta-endorphin values in the postdialysis samples. The similarity of plasma beta-endorphin, ACTH and cortisol levels in patients with end-stage renal disease before dialysis and in normal controls indicated integrity of the hypothalamic pituitary-adrenal axis. The significantly increased levels after the dialysis session and the significant correlation between postdialysis plasma beta-endorphin and ACTH suggest that the haemodialysis session was a stressful event.

Dynamic Exercise Induces Elevation of Plasma Levels of Endothelin-1 in Patients with Coronary Artery Disease

In this investigation the response of endothelin-1 plasma levels to dynamic exercise in patients with coronary artery disease (CAD) was studied. The study population consisted of 20 patients with CAD, 16 men and 4 women (mean age 53 ±8.6 years). Seven normal volunteers all men (mean age 53.4 ±4.4 years) were studied as a control group. Seven patients had prior myocardial infarction. All patients and controls exercised on a multi stage bicycle ergometer; plasma endothelin-1 levels and hemodynamic indices were measured at rest, at peak exercise, and at two and six minutes after exercise. Of the 20 patients examined, 7 (35%) showed electrocardiographic (ECG) signs of myocardial ischemia during the stress test. The mean plasma endothelin-1 concentration increased significantly from 7.8 ±3.0 to 13.6 ±3.5 pg/mL at exercise peak (P < 0.05) only in patients who did not show ECG signs of myocardial ischemia and returned to baseline values during recovery (six minutes) (9.4 ±2.1 pg/mL). In normal subjects baseline endothelin-1 levels (9.4 ±4.2 pg/mL) were not significantly altered at peak exercise (10.8 ±4.7 pg/mL) and at recovery (11.3 ±3.6 pg/mL). The hemodynamic parameters were not correlated with the plasma endothelin-1 levels before, during, and after exercise in all groups. The present study demonstrated that the plasma levels of endothelin-1 in patients with CAD increased significantly during stress testing.

Plasma beta-endorphin and beta-lipotropin levels increase in well trained athletes after competition and non competitive exercise

Plasma ß-endorphin (ß-EP) and ß-lipotropin (ß-LPH) levels were measured in 15 healthy trained marathon runners. These hormones were evaluated in two different conditions: 1 — before (1 h) and after a marathon race (n = 10); 2 — before, during and after a prolonged (90 min) submaximal exercise (bicycle ergometer at 50% VO2 max) (n = 5). In these latter group plasma ß-EP and ß-LPH levels were measured every 15 min for 165 min. In all the athletes, both plasma ß-EP and ß-LPH levels were significantly higher after the end of the marathon race than in basal conditions (p < 0.01). The prolonged exercise with bicycle ergometer significantly stimulated plasma ß-EP and ß-LPH levels. Starting 60 min after the beginning of the exercise, plasma ß-EP and ß-LPH levels resulted significantly higher than basal values until the end of the exercise (p < 0.01 at 60, 75 and 90 min). These data confirming that marathon running is a potent stress stimulus, showed that the duration and related factors but not the work load may be considered critical in stimulating ß-EP and ß-LPH release during physical exercise.

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.