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Biomedical subjects

F Portaluppi

Publications and source records attributed to F Portaluppi.

At least 19 recordsLinked to original sources

Differences in blood pressure regulation of congestive heart failure, before and after treatment, correlate with changes in the circulating pattern of atrial natriuretic peptide.

The mechanisms underlying altered BP regulation in congestive heart failure are unknown. This study examines the possibility that differences in circadian blood pressure (BP) regulation between the normal and the failing heart correlate with changes in the circulating pattern of atrial natriuretic peptide (ANP). Twelve normotensive patients with coronary artery disease were studied over two separate 24-h periods, the first during acute exacerbation of congestive heart failure (radionuclide-determined ejection fraction at rest was less than 30%) and the second after therapy-induced functional recovery (ejection fraction was more than 40%). BP monitoring at 10-min intervals and intra-atrial blood samples for ANP assays at hourly intervals were obtained. Significant correlation between ejection fraction and the indexes of circadian BP variability (standard deviation of the 24-h pressure mean and day-night pressure difference) were found both before and after treatment. Ejection fraction was independent of the BP means (24-h, daytime and night-time). BP variability, 24-h mean and daytime mean were higher after treatment. ANP means were lower after treatment, whereas ANP variability was higher. The indexes of BP and ANP variability correlated both before and after treatment, whereas the BP and the ANP means were independent. These findings demonstrate that differences in BP regulation of CHF before and after effective treatment correlate with changes in the circulating pattern of ANP. We speculate that by modulating ANP release, the heart could be actively involved in BP regulation as part of the compensatory mechanisms aimed at protecting against circulatory overload.

Aged

Circadian rhythm of calcitonin gene-related peptide in uncomplicated essential hypertension.

OBJECTIVE: To assess the existence of an altered circulating pattern of calcitonin gene-related peptide (CGRP) in hypertension. DESIGN: The 24 h variation in plasma CGRP was measured and compared in 10 patients affected by uncomplicated essential hypertension and in nine age- and sex-matched healthy volunteers. The diurnal variations in blood pressure, atrial natriuretic peptide (ANP), plasma renin activity (PRA), plasma aldosterone and plasma cortisol were also assessed. METHODS: Recumbency studies were performed under standardized, drug-free conditions beginning at 0800 h. Venous samples were drawn every 4 h for 24 h and hormone levels were assessed with specific radioimmunoassays. The blood pressure was measured every 15 min with a SpaceLabs 90207 monitor. RESULTS: The mean 24-h plasma CGRP concentrations were significantly lower in the hypertensive group than in the control group. In both groups a circadian rhythm was present with the same pattern, but at a lower level in hypertension. A temporal sequence starting with the nocturnal rise in plasma CGRP concentrations and progressing with the elevations of ANP, PRA, and plasma aldosterone and cortisol was apparent in both groups. The nocturnal rise in the CGRP and ANP concentrations coincided with the blood pressure and the heart rate falls. CONCLUSIONS: Our data show that CGRP is lower than normal but maintains its circadian variability and its relationship with the diurnal variations in blood pressure and other hormones known to be active on the cardiovascular system.

Adult

delta-Opioid receptors and the secretion of growth hormone in man: effect of opioid delta-receptor agonist deltorphin on GH responses to GH-releasing hormone and insulin-induced hypoglycemia.

To investigate the role of delta-opioid receptors in the modulation of growth hormone (GH) secretion, we compared in normal subjects the effect of the highly selective delta-opioid receptor agonist Deltorphin (DT) on the GH secretion responses to pituitary (GH-releasing hormone, GHRH)- and hypothalamic (insulin-induced hypoglycemia, IIH)-mediated stimuli. DT blunted the GH response to IIH, whereas it had no effect on the GH response to GHRH. It is concluded that in man DT-induced activation of delta-opioid receptors exerts an inhibitory action on hypoglycemia-stimulated GH secretion. Based on the lack of an effect of DT on the GH response to GHRH, we suggest that DT may modulate the secretion of GH through suprapituitary mechanisms.

Adult

Loss of nocturnal increase in plasma concentration of atrial natriuretic peptide in hypertensive chronic renal failure.

Diurnal change of plasma atrial natriuretic peptide (ANP) concentration was investigated in 12 patients with hypertension due to chronic renal failure (CRF) and in 12 patients with essential hypertension (EH) of comparable degree. Blood pressure (BP) monitoring was performed at 15-min intervals, while peripheral blood samples were obtained at 4-hour intervals starting from 8.00 h. The mean 24-hour plasma levels (+/- SEM) of ANP were 24.3 +/- 1.8 pmol/l in EH and 23.4 +/- 1.2 pmol/l in CRF. In EH, plasma ANP concentration was highest at 4.00 h (33.5 +/- 0.8 pmol/l) and lowest at 16.00 h (15.5 +/- 0.6 pmol/l). In CRF, no significant circadian change was present (22.2 +/- 3.1 and 20.4 +/- 3.6 pmol/l, respectively), and the nocturnal fall in BP was lost. Our data demonstrate that in CRF the loss and possible reversal of the nocturnal decline in BP is associated with the disappearance of any significant circadian variation in the circulating concentrations of ANP. These findings suggest a role for ANP in the alteration of BP variability of CRF, possibly mediated by autonomic dysfunction, and are further evidence for the existence of a relation between the circadian rhythms of ANP and BP.

Adult

Effect of deltorphin on pituitary-adrenal response to insulin-induced hypoglycemia and ovine corticotropin-releasing hormone in healthy man.

To determine the role of delta-opioid receptors in the modulation of hypothalamic-pituitary-adrenal activity, we studied in normal subjects the effect of the highly selective delta-opioid receptor agonist deltorphin (DT) on the secretion of ACTH, cortisol, and arginine vasopressin in response to insulin-induced hypoglycemia. In an attempt to clarify the site of opiate modulation of ACTH secretion, we also studied in normal subjects the effect of DT on the ACTH response to ovine CRH-41. DT blunted the ACTH, cortisol, and arginine vasopressin responses to insulin-induced hypoglycemia, whereas it had no effect on the ACTH and cortisol responses to CRH. We conclude that DT-induced activation of delta-opioid receptors exerts an inhibitory influence on hypoglycemia-stimulated ACTH secretion. Based on the lack of an effect of DT on the ACTH response to CRH, we postulate that DT may modulate the secretion of ACTH through suprapituitary mechanisms.

Adrenocorticotropic Hormone

Loss of nocturnal decline of blood pressure in hypertension due to chronic renal failure.

The aim of this study was to assess the blood pressure profile of chronic renal failure in comparison with essential hypertension. Thirty hypertensive patients with chronic renal failure due to non-vascular nephropathies were matched by age, sex, and mean 24 h blood pressure, with 30 patients affected by uncomplicated mild-to-moderate essential hypertension. They were studied in an open hospital ward. Diet, meal times, sleep times, and activity schedules were standardized. Noninvasive, automatic, blood pressure recordings were performed for 48 h at sampling intervals of 15 min. The mean 24 h blood pressure almost coincided in the two groups. However, in essential hypertension a mean (+/- SD) nocturnal fall of systolic and diastolic blood pressure was found (12.7 +/- 3.8 and 12.9 +/- 4.8 mm Hg, respectively), while renal patients displayed an average nocturnal increase of 2.7 +/- 8.9 mm Hg and 3.7 +/- 7.8 (P less than .001). The renal patients had also higher heart rates, with a significantly blunted nocturnal fall (4.4 +/- 4.5 beats/min as compared to 9.3 +/- 3.1 beats/min of essential hypertension; P less than .001). Among the renal patients, the day-night blood pressure changes showed no significant correlation with age, creatinine clearance, hematocrit, nocturnal change in heart rate, or day or night mean blood pressure levels. These data suggest that an abnormal day-night pattern of blood pressure is present in chronic renal failure patients independently from external interfering factors. Hence, casual measurements of blood pressure confined to daytime may underestimate a hypertensive condition associated with chronic renal failure.

Adult

Plasma levels of atrial natriuretic peptide are increased in normotensive postmenopausal women as a function of age.

The aim of this study was to assess the changes in atrial natriuretic peptide (ANP) levels before and after menopause and to test whether they depend on age or are an integral part of the hormonal changes in menopause. We measured plasma ANP, plasma renin activity (PRA), plasma aldosterone, serum estradiol-17 beta and progesterone concentrations in 103 normotensive women, either in premenopause (n = 35; mean age: 24 years), in physiological menopause (n = 34; mean age: 43 years) or surgically induced menopause (n = 34; mean age: 55 years). The last two groups were matched for duration of menopause and were comparable in their estrogen and progesterone status. PRA and plasma aldosterone concentrations decreased in postmenopausal women, whereas systolic blood pressure and ANP increased. These results were not confirmed after adjustment for age by covariance analysis. In all of the groups, plasma ANP concentrations were not significantly correlated with systolic or diastolic blood pressure, nor with plasma aldosterone, estrogen and progesterone concentrations. These correlations were not improved by correction for age. Plasma ANP concentrations were consistently correlated with age. These data suggest that the increase in plasma ANP levels found in postmenopausal women is related with age and that ANP does not play a direct role in the physiological hormonal changes of menopause.

Adult

Circadian profile of plasma calcitonin gene-related peptide in healthy man.

Calcitonin gene-related peptide (CGRP) is known to exert potent cardiovascular effects and is presumed to participate in the neural control of circulation and blood flow. It has been assayed in many physiological and disease conditions, yet virtually nothing is known of the normal fluctuations in its circulating levels. We have studied the variability throughout a 24-h period of plasma concentrations of CGRP in eight recumbent healthy volunteers (four men and four women, 25-37 yr old), after careful standardization of their daily diet and routine schedules. A correlation with the circadian rhythms of blood pressure (BP), heart rate (HR), and plasma aldosterone (PA), PRA, plasma cortisol (PC), and atrial natriuretic peptide (ANP) was also made. Plasma CGRP concentrations ranged from a mean peak value of 18.1 +/- 1.5 pmol/L to a mean lowest value of 11.7 +/- 0.4 pmol/L (P less than 0.05). The mean circadian acrophase of CGRP (calculated by cosinor analysis to occur at 2314 h) anticipated the corresponding acrophases of the other hormones (0122, 0528, 0809, and 0840 h for ANP, PRA, PA, and PC, respectively). Instead, BP and HR rhythms seemed to be antiphasic with the ANP rhythm (calculated acrophases occurred at 1356, 1339, and 1314 h for systolic BP, diastolic BP, and HR, respectively). Our data demonstrate that, like many other hormones, CGRP circulates in plasma with a circadian rhythm. There seems to be a temporal sequence starting with the nocturnal rise in plasma CGRP concentrations and progressing with the ensuing elevations of ANP, PRA, PA, and PC, whereas BP and HR are kept to their lowest values. These findings are in favor of a physiological role of CGRP in the complex regulation of BP homeostasis.

Adult

Consistent changes in the circadian rhythms of blood pressure and atrial natriuretic peptide in congestive heart failure.

We demonstrated in previous works that the circadian rhythms of blood pressure (BP) and atrial natriuretic peptide (ANP) are antiphasic in normal subjects and in essential hypertension. The aim of the present study was to assess the circadian rhythms of BP and ANP in 20 patients with stable congestive heart failure (CHF), divided into two groups of 10 according to their New York Heart Association functional class. A matched control group of 10 normal volunteers was also studied. Noninvasive BP monitoring at 15-min intervals was performed for 24 h. Peripheral blood samples were also obtained at 4-h intervals starting from 08:00 h. The mean (+/- SEM) circadian mesors of ANP plasma levels were 13.4 +/- 1.7 pmol/L in the control group, 28.6 +/- 2.4 pmol/L in the group of 10 patients in class II, and 81.5 +/- 12 pmol/L in the group of 10 patients in class III-IV. In normal subjects, plasma ANP concentration was highest at 04:00 h (21.5 +/- 2.7 pmol/L) and lowest at 16:00 h (8.8 +/- 2.4 pmol/L; p less than 0.01). Both groups of patients with CHF showed no significant circadian change in the plasma levels of ANP and also a significantly blunted circadian rhythm of BP. Cosinor analysis confirmed the loss of the circadian rhythms of ANP and BP in CHF patients. Our findings support the existence of a causal relationship between the circadian rhythms of ANP and BP.

Adult

Atrial strain is the main determinant of release of atrial natriuretic peptide.

We studied the response of atrial natriuretic peptide to the hemodynamic and renin-aldosterone variations occurring in four patients who developed cardiac tamponade, either occurring in idiopathic fashion in one or secondary to metastatic involvement of the pericardium in three. Right atrial pressure, heart rate and arterial blood pressure were monitored and serial blood samples were taken before and over three hours after pericardiocentesis. During cardiac tamponade, normal levels of atrial natriuretic peptide (mean +/- SEM: 54 +/- 7.4 pg/ml) were observed in the plasma despite increased right atrial pressure (23 +/- 3.8 cm H2O) and heart rates (98 +/- 4.4). Removal of pericardial fluid (540 to 1160 ml) was associated at first with a 200% increase in plasma concentrations of atrial natriuretic peptide (108 +/- 8.8 pg/ml; P less than 0.001), then with a gradual decline toward normal levels, simultaneous with the normalization of right atrial pressure and heart rate. Activity of renin and concentrations of aldosterone in the plasma were increased during tamponade and returned gradually to normal after pericardiocentesis (3.8 +/- 0.9 to 1.2 +/- 0.3 ng/ml/h and 20 +/- 4.2 to 9 +/- 3.2 ng/dl, respectively; P less than 0.01). These data confirm that atrial strain, not intracavitary pressure in itself nor heart rate, is the main determinant of the acute release of atrial natriuretic peptide, which is associated with a suppressing effect on the renin-aldosterone system. In addition, our data indicate that secretion of atrial natriuretic peptide during cardiac tamponade is not stimulated by secondary hyperaldosteronism.

Adult

Circadian rhythms of atrial natriuretic peptide, renin, aldosterone, cortisol, blood pressure and heart rate in normal and hypertensive subjects.

The occurrence and extent of a circadian rhythm in the circulating concentrations of atrial natriuretic peptide (ANP) are still matters of controversy. Only a few data are available in humans relating the time structure of plasma ANP levels with the circadian patterns of other hormones and cardiovascular variables. In a group of hospitalized normal volunteers (six men and four women, 16-76 years old), and in a group of hospitalized hypertensives (seven men and three women, 18-76 years old), we investigated the circadian variability of ANP and its temporal relationship with the circadian rhythms of blood pressure (BP) and heart rate (HR), and plasma renin activity (PRA), plasma aldosterone (PA) and plasma cortisol (PC) levels, by using a chronobiological inferential statistic method. At the end of a synchronizing period of 1 week (the diet and daily schedule were standardized), the subjects underwent automatic BP and HR monitoring, and blood sampling for 24 h. A statistically significant mean circadian rhythm was demonstrated for ANP, BP, HR, PRA, PA and PC in both normal and hypertensive subjects. The mean circadian acrophase of ANP (calculated to occur at around 04.00 h) anticipated the corresponding acrophases of the other hormones; BP and HR rhythms appeared to be in antiphase with ANP rhythm, i.e. the peak of BP and HR rhythms more or less coincided with the trough in ANP rhythm. A significant increase in the daily levels (assessed by the circadian mesor) of ANP was present in hypertensive subjects when compared with normal controls. In essential hypertension the circadian rhythm of ANP was set at higher circulating levels, but otherwise it was similar to the circadian rhythm found in normals. ANP mesors correlated significantly with renin and aldosterone mesors in normal subjects but not in hypertensive patients. ANP appears to anticipate awakening in its circadian periodic rise. On the basis of the considerable acrophase asynchronism, it seems possible to exclude any causal relations between the periodic changes of ANP and the rhythmic fluctuations of the other hormones that we studied. In contrast, important relations may be hypothesized between ANP levels and BP and HR values, on the basis of their antiphase rhythms.

Aldosterone

Are we overtreating hypertensive patients? Chronobiologic vs. sphygmomanometric evaluation of ambulatory antihypertensive therapy.

The purpose of this prospective study was to compare two methods of evaluating antihypertensive treatment efficacy: the traditional sphygmomanometric method and automatic home recording. Thirty hypertensive patients were studied who had been on antihypertensive therapy for at least 3 months. In the first 3 weeks of study their therapy was left unchanged and their diastolic blood pressures, measured with the traditional sphygmomanometer (weekly morning visit in the outpatient clinic; three successive recordings at 5-min intervals; subject seated), were always higher than 95 mmHg. During the following 8 weeks, the physician tried to reduce diastolic blood pressure to not greater than 90 mmHg by changing or increasing the therapy. Before and after any modification in therapy, noninvasive, automatic home, blood pressure monitorings for 24 hours were obtained and analyzed with Halberg's method of single cosinor, but were not made available to the physician until the end of the study. Automatic recordings showed that 18 patients had already had a circadian diastolic mesor less than or equal to 90 mmHg under the original drug regimen. By changing or increasing the therapy, no additional pressure decrease was seen in the home pressure recordings of the whole group of patients, whereas the sphygmomanometric diastolic pressures of 15 patients fell under 90 mmHg. Our study provides additional evidence that casual sphygmomanometric measurements can be misleading when one tries to assess the efficacy of antihypertensive therapy, and a cause of potential overtreatment.

Adrenergic beta-Antagonists

[Eosinophilic cellulitis (Wells' syndrome)].

The Authors report a case of eosinophilic cellulitis (Wells' syndrome). The patient was a 61 year old woman, diabetic, with a cardio-respiratory insufficiency and a maniaco-depressive psycosis. She presented, on the upper arms and trunk, a cutaneous eruption of erythematous-urticarial plaques, that histopathologically were characterized by a dermic leukocyte population, with a prevalence of eosinophils, distributed in the perivascular site. Laboratory tests revealed eosinophilia and circulating immune complexes. The etiopathogenesis of the disease is discussed as is the possible role of immune complexes in eosinophilic cellulitis.

Cellulitis

Altered circadian rhythms of blood pressure and heart rate in non-hemodialysis chronic renal failure.

The extended use of ambulatory monitoring has permitted the identification of many conditions in which the circadian rhythm of blood pressure is altered. The common denominator seems to be an impairment of the autonomic nervous system function. We examined whether the circadian blood pressure rhythm is altered in chronic renal failure (where autonomic dysfunction is usually present) by using a standardized chronobiological inferential statistical method in hospitalized subjects. For this purpose, a group of 30 non-hemodialysis hypertensive patients with chronic renal failure was compared with a second group of 30 patients affected by uncomplicated mild-to-moderate essential hypertension. The two groups were matched by age, sex and circadian mesors of blood pressure. Diet, meal times, sleep, and activity logs were standardized. Blood pressure and heart rate recordings were obtained by using an automatic oscillometric recorder and subsequently analyzed according to the cosinor method. A mean circadian rhythm of blood pressure was documented in both groups, but while the mean acrophases occurred between 2 and 3 p.m. in essential hypertension, in renal failure they were between 11 p.m. and midnight for blood pressure and around 7 p.m. for heart rate. In addition, the mean circadian amplitudes were significantly lower in renal failure, while the mean circadian mesor of heart rate was significantly higher. Our data demonstrate that the circadian rhythms of blood pressure and heart rate are altered also in hypertension due to chronic renal failure.

Adult

Chronobiologic vs. sphygmomanometric assessment of hypertension in a hospital setting.

The aim of this study was to assess the possible correlations between casual measurements and automatic monitoring analyzed with the chronobiologic technique in hospitalized hypertensive patients. Forty-three patients (24 men and 19 women) with mild to moderate essential hypertension were studied in an open hospital ward 5 to 7 days after admission. Meal times, sleep times, and visiting hours were standardized. A clinical value of blood pressure was calculated as the arithmetic mean of three sphygmomanometric measurements taken in the morning (patient seated; 5-min interval between measurements). Then, a basal value of blood pressure was considered as the lowest systolic and the lowest diastolic blood pressure among six sphygmomanometric measurements obtained every 5 min (patient supine). Noninvasive, automatic recording of blood pressure was also obtained every 15 min for 24 hours by a quasiportable oscillometric instrument. Blood pressure recordings were analyzed according to the "cosinor" method of Halberg. On average, clinical blood pressure was 160/96 +/- 14/10 mmHg, significantly higher (p less than 0.005) than either basal blood pressure (150/91 +/- 12/8 mmHg) or 24-h recorded blood pressure mesor (144/88 +/- 13/9 mmHg). The differences were not entirely due to diurnal variations, since morning casual measurements were significantly higher than daytime average blood pressure. A chronobiologic assessment of hypertension in hospitalized patients is more representative of true blood pressure behavior, not only because of the multiple recordings but also because of the absence of an alarm reaction that may trigger a pressor response.

Adult

Circadian rhythms of atrial natriuretic peptide, blood pressure and heart rate in normal subjects.

The occurrence and extent of a circadian rhythm in the circulating concentrations of atrial natriuretic peptide (ANP) is still a matter of controversy. In a group of hospitalized normal volunteers (6 men and 4 women, 16-76 years old), we investigated the circadian variability of ANP and its temporal relation with the circadian rhythms of blood pressure (BP) and heart rate (HR), by using a chronobiological inferential statistical method. At the end of a synchronizing period of 1 week (the diet and the daily schedule were standardized), the subjects underwent automatic BP and HR monitoring, and blood sampling for 24 h. A statistically significant mean circadian rhythm was demonstrated for ANP, BP, and HR. The mean circadian acrophase of ANP was calculated to occur around 4 a.m. BP and HR rhythms appeared to be in antiphase with ANP rhythm, i.e. the peak of BP and HR rhythms more or less coincided with a trough in ANP rhythm. ANP appears to be anticipatory in its circadian periodic rise to awakening. Therefore, postural changes cannot fully account for the diurnal variations observed.

Adolescent

Ergometric evaluation of the effects of enalapril maleate in normotensive patients with stable angina.

The anti-ischemic effect of a single oral dose of 10 mg of enalapril maleate (E) was investigated in 14 normotensive patients with coronary artery disease (CAD) and stable effort-induced angina pectoris. An exercise stress test was performed three times in each patient at the same clock hour on three successive days: with no treatment (baseline), 6 h after administration of placebo (P), and 6 h after oral administration of a single 10 mg dose of E. The multistage nonstop effort tests were performed in the sitting position. Workload started at 25 W and was increased by 25 W every 2 min until an ischemic ST depression of more than 1.5 mm was observed. The following parameters were measured: heart rate (HR), systolic blood pressure (BP), rate-pressure product (RPP), workload sustained (WS), elapsed time of effort (ET), and millimeters of ischemic ST depression. The values of the parameters observed with baseline, P, and E were compared at the moment of appearance of chest pain or ischemic ST depression, at the moment of maximal effort, maximal common WS (MCWS), and maximal common RPP (MCRPP). Enalapril delayed the appearance of the ischemic ST depression. At the MCWS, the RPP was significantly lower under E and the ST depression was less marked; this effect was the result of a lower BP level, in the absence of any significant change in HR response. The acute effects of E observed in normotensive patients with effort-induced angina pectoris seems to be related to the inhibition of angiotensin at the coronary level and to its antiadrenergic action.

Angina Pectoris

Does placebo lower blood pressure in hypertensive patients? A noninvasive chronobiological study.

Placebo controlled trials have generally been used in order to evaluate the antihypertensive efficacy of drugs. There is some evidence, though, that blood pressure might not be influenced by placebo. Non-invasive devices for automatic blood pressure monitoring are likely to provide a better assessment of blood pressure response to drugs, as well as to different physiologic and pathologic conditions, than the traditional sphygmomanometric devices. The aim of this study was to investigate the effect of placebo on blood pressure recorded automatically and non-invasively. For this purpose, a chronobiologic approach to the collection, evaluation and interpretation of data seemed most appropriate. A group of 12 patients with a clinical diagnosis of essential hypertension underwent automatic blood pressure monitoring in hospital for 4 days. Measurements were taken every 15 min by an oscillometric instrument with an automatically inflated cuff. After a washout period during which the patients received no treatment, pressure recording was undertaken under basal conditions for 2 days. On the third and fourth days of study, the patients received 2 tablets of placebo, one at 10 a.m. and one at 10 p.m. In each patient a highly significant circadian rhythm was documented for systolic and diastolic pressure, both under basal conditions and during placebo administration. Blood pressure mesors were higher than reference standards and were not significantly affected by placebo. The circadian amplitudes and acrophases did not differ significantly before and during placebo. Our data indicate that automatically recorded blood pressure is not influenced by placebo.

Adult