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Biomedical subjects

F Veglio

Publications and source records attributed to F Veglio.

At least 55 records · Page 3Linked to original sources

Impaired cortisol binding to glucocorticoid receptors in hypertensive patients.

We compared glucocorticoid receptor binding characteristics and glucocorticoid responsiveness of human mononuclear leukocytes (HML) from hypertensive patients and matched normotensive volunteers. We also considered associations of these variables with plasma renin activity, aldosterone, cortisol, corticotropin, and electrolyte concentrations. We calculated binding affinity (Kd; nmol/L) and capacity (Bmax; sites/cell) for dexamethasone and cortisol from homologous and heterologous competition curves for specific [3H]dexamethasone binding sites on HML isolated from the blood of normotensive volunteers and subjects with essential hypertension. Glucocorticoid responsiveness of HML was evaluated as IC50 values (nmol/L) for dexamethasone and cortisol for the inhibition of lysozyme release. We measured plasma hormones by radioimmunoassay. Kd values (mean+/-SE) for cortisol in HML of hypertensive patients were higher than in control subjects (24.6+/-2.4 versus 17.5+/-1.7 nmol/L, P<.04). Binding capacity (4978+/-391 versus 4131+/-321 sites/cell), Kd values for dexamethasone (6.7+/-0.5 versus 5.7+/-0.3 nmol/L), and IC50 values for dexamethasone (3.4+/-0.3 versus 3.1+/-0.2 nmol/L) and cortisol (12.2+/-1.6 versus 9.5+/-0.3 nmol/L) were not significantly different. Patients with renin values less than 0.13 ng angiotensin I/L per second were markedly less sensitive to cortisol than those with higher values. Both Kd (30.3+/-2.5 versus 19.2+/-2.4 nmol/L) and IC50 values (15.5+/-1.8 versus 8.9+/-1.2 nmol/L) for cortisol were significantly higher in patients with lower renin values (P<.03). Other variables, including plasma hormone and electrolyte values and binding characteristics for dexamethasone, were not different. These data suggest that cortisol binding to glucocorticoid receptor is slightly impaired in patients with essential hypertension. In vivo, this could lead to inappropriate binding of cortisol to mineralocorticoid receptors. Hence, decreased sensitivity to cortisol is associated with renin suppression. This hypothesis is supported by evidence of hypertension and low renin activity, which others have described in patients with primary glucocorticoid resistance due to mutations of the glucocorticoid receptor.

Adult↗

Dopamine D3 receptor in peripheral mononuclear cells of essential hypertensives.

Dopamine D3 receptor was studied in peripheral mononuclear cells of high-normal, stage 1, stage 2, and stage 3 essential hypertensives using a radioligand binding assay technique with [3H]-7-hydroxy-N,N-di-n-propyl-2-aminotetraline (7-OH-DPAT) as a radioligand. A group of de novo Parkinsonian patients was also examined as a reference group of impaired dopaminergic function. [3H]-7-OH-DPAT was bound specifically to human peripheral mononuclear cells in a manner consistent with the labeling of a dopamine D3 receptor. No changes in free dopamine, norepinephrine, epinephrine and aldosterone levels, renin activity, dissociation constant of [3H]-7-OH-DPAT binding, or the pharmacological profile of [3H]-7-OH-DPAT binding were found between normotensive control subjects and essential hypertensives or Parkinsonians. The density of peripheral mononuclear cell [3H]-7-OH-DPAT binding sites increased in essential hypertensives parallel to blood pressure value augmentation. A higher density of [3H]-7-OH-DPAT binding sites was found in Parkinsonians. In these patients, the density of [3H]-7-OH-DPAT binding sites was similar to that observed in high-normal subjects and in stage 1 essential hypertensives. The increased density of peripheral mononuclear cell dopamine D3 receptor in hypertension as well as in Parkinson's disease may represent an upregulation mechanism consequent to impaired dopaminergic function. In view of the difficulty in identifying markers of peripheral dopamine function, analysis of dopamine D3 receptor in peripheral mononuclear cells may help evaluate whether the dopaminergic system is involved in hypertension.

Adult↗

Pharmacological characterisation of Ca2+ channels of the L-type in human peripheral blood lymphocytes.

Ca2+ channels of the L-type were characterised in intact human peripheral blood lymphocytes using a radioligand binding technique and the dihydropyridine-type Ca2+ channel antagonist [3H](+)-PN 200-110 (isopropyl-4-(2,1,3-benzoxadiazol-4-yl)1,4-dihydro-5-methoxycarbon yl-2, 6-dimethyl-3-pyridine carboxylate) as a ligand. [3H](+)-PN 200-110 binding to human peripheral blood lymphocytes was time-, temperature-, concentration-dependent and of high affinity. The dissociation constant (Kd) value was 0.4 +/- 0.02 nM and the maximum binding capacity (Bmax) was 33.5 +/- 1.6 fmol/10(6) cells. Pharmacological analysis of [3H](+)-PN 200-110 binding to human peripheral blood lymphocytes was consistent with the labelling of a Ca2+ channel of the L-type. In fact, dihydropyridine derivatives were the most potent competitors of [3H](+)-PN 200-110 binding, whereas phenylalkylamine and benzothiazepine compounds or non-selective Ca2+ channel modulators were weak or ineffective displacers. These findings are the first observation that human peripheral blood lymphocytes express Ca2+ channels of the L-type. The possibility that Ca2+ channel antagonists may interfere with immune system function is discussed.

Adult↗

Weighted Fourier analysis of blood pressure curves after lisinopril versus atenolol administration in young hypertensives.

OBJECTIVE: To evaluate and compare the effects of lisinopril versus atenolol administration on the diurnal blood pressure profile and the nocturnal blood pressure fall in young mild-to-moderate essential hypertensives.METHODS: Thirty patients were studied. After a 2-week placebo run-in period, they were single-blind randomly assigned to receive 20 mg lisinopril or 100 mg atenolol. Using a SpaceLabs 90207 device, their ambulatory blood pressure was measured before and after 12 weeks of therapy. The readings were analysed using Fourer series with four harmonics. RESULTS: Lisinopril and atenolol administration significantly decreased office and ambulatory blood pressure values compared with the placebo period. The daily blood pressure curves obtained from Fourier analysis showed that the circadian rhythm was not altered by lisinopril and atenolol administration. From the night:day ratio for the nocturnal blood pressure fall, we found that atenolol administration minimized the average night-time blood pressure dip by increasing the number of non-dippers. In contrast, lisinopril administration did not modify the day-night difference, preserving the nocturnal blood pressure fall. CONCLUSION: Lisinopril and atenolol administration as a first-step treatment of young essential hypertensives produced comparable degrees of diurnal control of arterial pressure. The blood pressure fall at night in patients treated with atenolol was slightly less than that found with lisinopril treatment.

Journal Article↗

Levels of plasma neuropeptide Y and other vasoactive substances during head-up tilt in normal and essential hypertensive subjects.

Neuropeptide Y, a potent vasoconstrictor peptide with 36 amino acid residues, is co-stored and released with catecholamines in sympathetic nerve endings. In this study responses in circulating neuropeptide Y induced by baroreceptor activation during change from the supine to the head-up position was measured in normal subjects and untreated essential hypertensives. Furthermore, the relationships with plasma catecholamines, endothelin-1, renin and serotonin were studied. No significant differences of plasma neuropeptide Y were found between normotensive and hypertensive subjects, before or after postural changes, and there was no correlation with a range of the vasoactive substances studied. Our results suggest that plasma neuropeptide Y does not increase with noradrenaline on sympathetic activation during postural stress both in normals and in hypertensive subjects. In man, measurement of plasma neuropeptide Y during head-up tilt does not provide a useful estimation of sympathetic nervous activity.

Adult↗

Radioligand binding characterization of putative dopamine D3 receptor in human peripheral blood lymphocytes with [3H]7-OH-DPAT.

The presence and the pharmacological profile of dopamine D3 receptor have been investigated in human peripheral blood lymphocytes using radioligand binding techniques and the selective dopamine D3 receptor agonist [3H]7-hydroxy-N,N-di-n-pro-pyl-2-aminotetralin ([3H]7-OH-DPAT) as a ligand. [3H]7-OH-DPAT binding to human peripheral blood lymphocytes was time-, temperature-, and concentration-dependent and of high affinity with a dissociation constant value (Kd) of 0.27 +/- 0.05 nM and a maximum binding density (Bmax) of 14.7 +/- 0.06 fmol/2 x 10(6) cells. Binding was also reversible. The rank order of potency of displacers of [3H]7-OH-DPAT binding to human peripheral blood lymphocytes resembled that found for dopamine D3 receptor in rat brain homogenates or in rat or human cell lines. Our findings, which are consistent with those of other authors performed with molecular biology techniques, suggest that human peripheral blood lymphocytes express dopamine D3 receptor. In the brain, dopamine D3 receptor probably mediates the anti-psychotic effect of neuroleptics. The availability of a rapid and reproducible technique for its assay may contribute to evaluate its status in brain disorders characterized by impaired dopaminergic neurotransmission.

Humans↗

Spectral characteristics of heart rate and blood pressure variability in primary aldosteronism.

A disturbance of the autonomic cardiovascular function has been postulated in primary aldosteronism as a possible mechanism for hypertension. Using the method of spectral analysis of heart rate and blood pressure variability, the aim of this study was to assess sympathovagal interactions modulating cardiovascular function and baroreflex control in patients with primary aldosteronism. Seventeen patients (7 with adenomas and 10 with idiopathic hyperaldosteronism) and a control group of 11 essential hypertensives (EH) and 10 normotensive subjects were studied. Continuous finger blood pressure was measured using a Finapres device and heart rate was measured using an electrocardiographic monitor. The studies were conducted in each patient for 20 min in the supine position and 10 min during a passive head-up tilt to 60 degrees. The low frequency and the low frequency-to-high frequency ratio of systolic and diastolic blood pressures were significantly higher both in primary aldosteronism and in EH patients compared with normotensives (P < .01). Impaired response to tilt was found in the heart rate and blood pressure variability in primary aldosteronism and EH patients; the increase in low frequency was smaller than in normotensives. Baroreflex gain (assessed by alpha index) was less in primary aldosteronism and EH patients as compared with normotensives. These findings may suggest that volume expansion or sympathetically mediated central translocation of the blood volume, or both, could stimulate the cardiopulmonary receptors and impair the baroreflex gain. Our findings suggest that an enhanced peripheral vascular responsiveness to a normal sympathetic outflow may be involved in the pathogenesis of hypertension in primary aldosteronism.

Baroreflex↗

Assessment of renal resistance index after captopril test by Doppler in essential and renovascular hypertension.

Ultrasonic duplex scanning has been validated as a noninvasive method to evaluate the kidney arteries and hemodynamic characteristics of renal blood flow in patients with renal artery stenosis. The purpose of our study was to assess the changes in renal vascular impedance in 22 patients with renovascular hypertension, as compared with 45 essential hypertensives and 15 normotensives, by using the Doppler parameter resistance index (RI) before and after a captopril oral test. After the captopril test the delta RI decreased significantly in the stenotic artery (P < 0.05). Univariate analysis showed that PRA values after captopril correlated inversely with the changes of RI only in the stenotic artery (P < 0.05). Thus, our findings suggest that the application of the captopril test to renal echo-Doppler may represent a feasible, noninvasive, and inexpensively useful tool in the screening studies aimed at diagnosing renovascular hypertension.

Administration, Oral↗

Dopamine D5 receptor expression is unchanged in peripheral blood lymphocytes in essential hypertension.

The present study was designed to investigate possible changes in the expression of lymphocyte dopamine receptor in essential hypertension. The expression of dopamine D5 receptor was evaluated by radioligand binding techniques using [3H]-SCH 23390 as ligand. Plasma catecholamines, aldosterone levels and plasma renin activity were also measured. Eleven borderline hypertensive patients, 15 patient with the mild essential hypertension, 7 patients with moderate essential hypertension and 5 patients with severe essential hypertension were examined. Plasma catecholamine levels were assayed by high pressure liquid chromatography with electrochemical detection. Dopamine D5 receptor was measured by radioligand binding techniques. Plasma aldosterone levels and renin activity were determined by radio immunoassay. [3H]-SCH 23390 was specifically bound to human peripheral blood lymphocytes. The binding was time-, temperature- and concentration-dependent with a dissociation constant (Kd) value of 0.59 nM and a maximum density of binding sites (Bmax) of 223 pmol/10(6) cells. Dopamine competed with [3H]-SCH 23390 binding in the submicromolar range suggesting the labelling of a dopamine D5 receptor. No changes in the density of [3H]-SCH 23390 binding sites were observed in human peripheral blood lymphocytes between essential hypertensive patients and normotensive subjects. Also catecholamines, plasma renin activity and aldosterone levels were unchanged. In spite of the availability of a sensitive technique for measuring dopamine receptors in human peripheral lymphocytes, no change in their expression was noticeable in essential hypertension. This suggests that dopamine receptor analysis in essential hypertension is not a useful marker for investigating hypertension-dependent changes of the peripheral dopaminergic system.

Adult↗

Role of alcoholic beverages in essential hypertensive patients.

To evaluate the importance of alcohol and other environmental factors in essential hypertensives, we conducted a cross-sectional study on 627 patients (322 women, 305 men) subdivided in four subgroups according to sex and presence or absence of drug therapy, to evaluate differences due to drugs and changes in life style. Multiple regression analyses were run where systolic and diastolic blood pressures were considered as separate dependent variables with the following independent variables: age, body mass index, physical activity, alcohol and coffee consumption, smoking, educational level; considered as continuous or categorical variables. eighty-eight per cent of all patients showed a moderate-low alcohol intake (1-50 g/day); wine was the preferred beverage. We found a negative independent relationship between mild/moderate alcohol consumption levels and systolic blood pressure in untreated men and untreated women, and no relationship between alcohol and diastolic blood pressure in all subgroups considered. Body mass index and age were positively associated with both systolic and diastolic blood pressure. Our data suggest that mild to moderate alcohol consumption does not affect blood pressure control in either treated or untreated hypertensive patients.

Age Factors↗

Cardiovascular risk factors in adolescence: prevalence and familial aggregation.

BACKGROUND: In the field of primary prevention there is an increasing interest in screening pediatric populations for cardiovascular risk factors. The aim of this study was to determine the overall prevalence of high blood pressure (HBP), obesity, and sedentariness in a population of adolescents. The presence of familial aggregation for these factors was also evaluated. METHODS: The prevalence of HBP, obesity, and low physical activity was determined in 1413 adolescents ages 12-15 years (705 males, 698 females) randomly selected from Turin school children. The prevalence of HBP and obesity in parents was determined. RESULTS: One risk factor was found in 40.9% of females (2.4% HBP, 8.6% obesity, and 29.9% sedentariness) and 39.6% of males (2.8% HBP, 16.4% obesity, and 20.4% sedentariness); the concomitance of two or three risk factors were present, respectively, in 9.9 and 2.7% of females and 10.9 and 1.1% of males with a strong association of obesity and HBP. A significant familial aggregation for obesity was found and no particular relationship was found for BP. CONCLUSION: The ability to identify children developing a single or multiple risk factors is an important contribution to the prevention of serious cardiovascular diseases in adulthood.

Adolescent↗

Statistical evaluation of circadian blood pressure rhythm during isradipine long-term therapy.

In this study, using the two-step truncated Fourier series with four harmonics, we analysed the diurnal blood pressure profile in 13 mild-moderate essential hypertensive patients during isradipine long-term therapy. Circadian parameters such as the amplitudes and phases of the four harmonics and the overall amplitude and phase were obtained from the model. The total duration of the study was 26 weeks. Ambulatory blood pressure was measured at 15-min, intervals using a Takeda TM 2420 device after 2 weeks of placebo and after 6 and 26 weeks of isradipine (5 mg daily) respectively. After 6 and 26 weeks therapy the blood pressure values showed a significant decrease, although the daily blood pressure curves obtained from Fourier analysis showed that the circadian rhythm was not altered by isradipine treatment. Both the night/day differences and the overall amplitude/acrophases were statistically significant at 0.6 and 26 weeks. According the nocturnal blood pressure fall, we found that long-term therapy with isradipine increased the number of patients with nocturnal blood pressure fall and reducing the early morning blood pressure rise. In conclusion, the two-step method Fourier analysis represents a novel and useful statistical approach to evaluate the presence of a significant diurnal blood pressure rhythm and to provide the circadian parameters of the 24-h blood pressure profile during pharmacological therapy.

Blood Pressure↗

Plasma immunoreactive endothelin-1 in primary hyperaldosteronism.

This study evaluated the assessment of plasma endothelin-1 (ET-1) levels in primary aldosteronism and its correlation with other vasoactive hormones such as renin, aldosterone, catecholamines, arginine-vasopressin, and atrial natriuretic peptide. Plasma ET-1 was measured in 12 patients with primary aldosteronism (five adenomas and seven primary hyperplasia) and in 15 normal subjects. No significant differences were found in plasma ET-1 between controls and hypertensive patients both in adenoma and primary adrenal hyperplasia (8.8 + 1.6 pg/mL v 6.2 + 1.4 pg/mL v 6.5 + 1.0 pg/mL, P = NS, respectively). Further, no significant correlations were found among ET-1 and vasoactive hormones. In conclusion, these findings show that there are no differences in ET-1 levels between primary aldosteronism patients and healthy subjects. Circulating ET-1 is not involved in the hypertension in primary aldosteronism.

Adenoma↗

Analysis of 24-h blood pressure profile by Fourier series during lacidipine therapy.

In the present study, we examined the circadian profile of blood pressure (BP) in 10 patients with moderate essential hypertension before and after 6 months of lacidipine therapy. Ambulatory BP was measured at 30-min intervals using SpaceLabs 90207. To account for the unequal time intervals between successive readings, BP means and variances were weighted for the time span between successive readings, and weighted linear-regression analysis was applied. The 24-h BP values were carried out using Fourier analysis, comparing the values from the baseline with those after 24 weeks of lacidipine. After 24 weeks BP values showed a significant decreased compared with baseline values (all p < 0.01). The daily BP curves obtained from Fourier analysis with four harmonics showed that the significant circadian rhythm in nine patients was not altered by lacidipine treatment. The night/day differences were statistically significant at 24 weeks vs. 0 week (all p < 0.01). The overall amplitude and acrophase of the BP curve were statistically significant at 24 weeks (all p < 0.01). After 24 weeks of lacidipine therapy, according to the nocturnal BP fall, we found three intermediate dippers, six dippers, and one non-dipper. By use of the two-step Fourier analysis method, which provides a formal and statistical method to evaluate the presence of a significant diurnal BP rhythm and parametrization of the 24-h BP recordings, we showed that lacidipine long-term therapy is effective in lowering BP and preserving the diurnal BP rhythm.

Antihypertensive Agents↗

Pharmacological characterization and autoradiographic localization of dopamine receptors in the human adrenal cortex.

The pharmacological characteristics and the anatomical localization of dopamine D1-like and D2-like receptors were studied in sections of the human adrenal cortex using radioligand binding and autoradiographic techniques. [3H]SCH 23390 was used as a ligand of D1-like receptors, whereas [3H]spiroperidol was used to label D2-like receptors. No specific [3H]SCH 23390 binding was detectable in sections of the human adrenal cortex. On the other hand, [3H]spiroperidol was bound to sections of the adrenal gland in a manner consistent with the labelling of dopamine D2-like receptor sites. The binding was time, temperature and concentration dependent, belonging in the range of concentrations of the radioligand used for a single class of high-affinity sites. The dissociation constant (Kd) averaged 2.7 nmol/l, whereas the maximum density of binding sites (Bmax) was 160 nmol/mg tissue. Experiments on the pharmacological specificity of [3H]spiroperidol binding to sections of the human adrenal cortex revealed that clozapine was the most powerful displacer of [3H]spiroperidol from sections of the human adrenal cortex. This suggests the presence in the human adrenal cortex of dopamine receptors of the D4 subtype. Light microscope autoradiography showed the highest density of specific [3H]spiroperidol binding sites in the zona glomerulosa and to a lesser extent in the zona reticularis. Only sparse [3H]spiroperidol binding sites were localized in the zona fasciculata. The possible functional consequences of this localization of dopamine D2-like receptor sites in the human adrenal cortex are discussed.

Adrenal Cortex↗

Plasma endothelin in NIDDM patients with and without complications.

OBJECTIVE: To measure plasma endothelin 1 (ET-1) levels in uncomplicated non-insulin-dependent diabetes mellitus (NIDDM) and investigate whether ET levels may be related to angiopathy, blood pressure, metabolic control, or duration of illness. RESEARCH DESIGN AND METHODS: Plasma levels of ET-1 were measured in 44 NIDDM patients, of whom 24 had uncomplicated diabetes, 20 had angiopathy, and 10 had hypertension. In 21 patients, the duration of illness was > 10 years, and in 23 the duration of illness was < 10 years. Serum creatinine levels, microalbuminuria, and HbA1c were determined simultaneously. Thirty normotensive healthy (nondiabetic) individuals (20 men and 10 women) served as control subjects. RESULTS: No significant statistical differences in plasma ET-1 levels were found among all diabetic patients, diabetic patients with and without angiopathy, diabetic patients with different durations of diabetes, and normal subjects. No significant correlation of plasma ET-1 with blood pressure, age, serum creatinine level, duration of diabetes, HbA1c, or diabetic complications was found. CONCLUSIONS: Plasma ET-1 levels are similar in patients with NIDDM and healthy subjects and do not seem to act as a marker of diabetic complications.

Adult↗

[Color-Doppler ultrasonography and hypertension. Functional assessment of the renal region].

Color-Doppler US can be used for the morphofunctional assessment of most arterial districts. In hypertension, color-Doppler US can be used to study the renal arteries for both the diagnosis of renovascular hypertension and better physiopathologic assessment of renal arterial blood flow in essential hypertension. To this purpose, we studied renal flow characteristics with the resistive index in both basal conditions and after pharmacologic stimulation with angiotensin-converting enzyme inhibitors. The resistive index was seen to rise in parallel with hypertension severity, as measured by mean arterial pressure; the change was statistically significant (p < 0.05). Values rose step by step from 57.4 (+/- 4.96) in the right renal artery and from 56.6 (+/- 4.18) in the left one in controls, up to 62.2 (+/- 6.6) in the right and 62.3 (+/- 7) in the left renal arteries of severe hypertensives. After pharmacologic stimulation in controls and in mild hypertensives, resistive index values rose significantly (+2.32 +/- 2.1 and +3.5 +/- 5.2, respectively), while in more advanced stages of the disease this index remained unvaried from a statistical point of view (+0.5 +/- 1.7 in moderate and -0.2 +/- 2.1 in severe hypertensives). These data can be explained by reduced capability of renal blood flow autoregulation, as a consequence of a defined vascular damage. In the follow-up of more severe stages of the disease, although pharmacologic treatment had been optimized and mean arterial pressure values reduced (109.08 vs. 118.25 mmHg), even after a prolonged therapeutic wash-out, an abnormal RI response persisted in controls (-1.79 +/- 2.62 vs. -0.94 +/- 1.64), due to persistent arteriolar damage. To date, it is still to be defined if our studies can be applied not only to populations but also to single patients.

Follow-Up Studies↗

Twenty-four-hour power spectral analysis by maximum entropy method of blood pressure in primary hyperaldosteronism.

In the present study we estimated the periodic profiles and variance structure of systolic blood pressure, diastolic blood pressure, heart rate and mean arterial pressure by using an autoregressive model of power spectrum, Maximum Entropy Method (MEM) in 8 patients with primary aldosteronism, during long-term therapy with nicardipine slow release. The four blood pressure variables were measured at 30-min intervals, using a noninvasive device (Spacelabs 90202) in 8 hypertensive patients of whom 6 with idiopathic aldosteronism (IHA) and 2 with dexamethasone-suppressible aldosteronism (DSH), before and after 24 weeks of 80 mg nicardipine daily. Blood pressure data were processed by MEM and spectral profiles were obtained. During nicardipine therapy all patients showed a significant decrease of 24-h ambulatory blood pressure values (p < 0.01). Before therapy, spectrum analysis by MEM indicated the presence of high frequency distribution of peaks for SBP, DBP, MAP and HR. The MEM power spectrum showed an increase in amplitude of sharp peaks of systolic, diastolic, MAP and heart rate in all patients after therapy at 24 h corresponding to the circadian rhythm blood pressure. Furthermore, the trend of these variables synchronized themselves in the same period after 24 weeks of nicardipine therapy, with spectral patterns of blood pressure similar to those of normotensive subjects. This chronobiologic approach, by Maximum Entropy Method, may be used as an alternative statistical analysis to search for possible rhythmic behavior of ambulatory blood pressure data before and after pharmacological treatment in secondary hypertensive patients.

Activity Cycles↗