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Biomedical subjects

F Veglio

Publications and source records attributed to F Veglio.

At least 37 records · Page 2Linked to original sources
PubMed2001

Angiotensin-converting enzyme and angiotensinogen gene polymorphisms are non-randomly distributed in oral contraceptive-induced hypertension.

OBJECTIVES AND METHODS: Oral contraceptives (OC) usage increases serum angiotensinogen levels to three to five times normal and about 5% of these women develop arterial hypertension. The genetic contribution to this susceptibility to OC-induced hypertension is poorly understood. We have analyzed the genotypes of 149 hypertensive and 101 normotensive women using oral contraceptives, for three genetic polymorphisms in genes of the renin-angiotensin system: an insertion/deletion (I/ D) in the angiotensin converting enzyme (ACE) gene, the T235M polymorphism of the angiotensinogen gene (AGT) and a point mutation in its promoter. RESULTS: After cessation of oral contraception the mean arterial pressures of the hypertensive women were separable into two non-overlapping groups; 88 of the women remained hypertensive and 61 returned to normal blood pressure. Both groups of hypertensive women had a similarly higher frequency of hypertensive relatives than the normotensive women, but were otherwise similar. The 235T allele of AGT was significantly increased in frequency in the 61 oral contraceptive-inducible hypertensive women compared with the controls and the 88 women that remained hypertensive. The ACE I/D genotypes were similarly distributed within the three groups of women, but were distinctly non-random in the oral contraceptive-induced hypertensive women when they were also classified by AGT genotype. CONCLUSION: This statistical interaction of genotype frequencies suggests that the genetic basis of susceptibility to OC-induced hypertension is complex.

Adult↗
PubMed2001

Alpha1-adrenergic receptor subtypes in peripheral blood lymphocytes of essential hypertensives.

OBJECTIVE: The expression of alpha1-adrenergic receptor subtypes in peripheral blood lymphocytes was investigated in 28 essential hypertensive patients as well as in the peripheral blood lymphocytes and aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. METHODS: Alpha1-adrenergic receptors were quantified by radioligand binding assays, employing [3H]-prazosin as the radioligand in association with compounds displaying different degrees of selectivity for alpha1A-, alpha1B- and alpha1D-adrenergic receptor subtypes. RESULTS: The affinity of [3H]-prazosin binding was similar in peripheral blood lymphocytes of different stage essential hypertensive and normotensive subjects or of SHR and age-matched normotensive WKY rats as well as in the aortas of SHR and WKY rats. The radioligand binding assay revealed no change in the expression of alpha1-adrenergic receptors in peripheral blood lymphocytes of essential hypertensives compared with normotensive subjects; a moderate decrease of alpha1B-adrenergic receptors and an increase of alpha1D-adrenergic receptors. The relative densities of the alpha1-adrenergic receptor subtypes were similar in the three groups of essential hypertensives. In peripheral blood lymphocytes and in aorta of SHR, [3H]-prazosin binding was significantly reduced compared with normotensive WKY rats. The expression of alpha1-adrenergic receptor subtypes in peripheral blood lymphocytes of SHR was similar to that found in peripheral blood lymphocytes of essential hypertensives. CONCLUSIONS: Changes of lymphocyte alpha1-adrenergic receptor subtypes in essential hypertensives are similar to those observed in lymphocytes and vascular tissues of animal models of hypertension. This suggests that assays of lymphocyte alpha1-adrenergic receptors may represent an indirect marker of their involvement in essential hypertension.

Adult↗
PubMed2001

Absence of D147E mutation of CYP11B2 gene in hypertensive patients with increased corticosterone and aldosterone production.

OBJECTIVE: 11beta-Hydroxylase and aldosterone synthase are two highly homologous genes involved in different forms of human hypertension and in different animal models of hypertension. It has been shown that the conservative substitution D147E in the human CYP11B2 gene results in an increased production of corticosterone and aldosterone in vitro. A gene conversion between the CYP11B1 and CYP11B2 genes could be responsible for such a substitution. METHODS: In this study we investigated the presence of the mutation D147E of CYP11B2 in a group of 128 patients with primary aldosteronism, 68 patients with essential hypertension and increased corticosterone production and in 48 normal volunteers. RESULTS AND CONCLUSIONS: We did not identify any patient carrying this mutation, indicating that if it exists it is very rare and so has no relevance in determining the increased steroid excretion seen in some subtypes of human hypertension.

Aged↗
PubMed2000

CYP11B2 gene polymorphisms in idiopathic hyperaldosteronism.

Primary aldosteronism is characterized by autonomous production of aldosterone and arterial hypertension, and it occurs in 2 principal forms: aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). APA can be cured through removal of the adenoma, whereas IHA leads to hypertension that must be treated with medication. The origin of the autonomous aldosterone production in IHA is poorly understood, but genetic factors may contribute to its cause. To test the hypothesis that variants of the aldosterone synthase gene may contribute to susceptibility to IHA, we compared genotypes at 3 polymorphic sites in the CYP11B2 gene in patients with IHA (n=90) with those found in patients with APA (n=38), in patients with essential hypertension (n=72), and in normotensive individuals (n=102). We observed significant linkage disequilibrium among the 3 polymorphisms with 2 frequent haplotypes in all groups studied. One haplotype (C2R) was found to be increased in frequency in the IHA group (47%) compared with the other groups, which had a similar haplotype frequency (36%). The 3 polymorphisms studied have been implicated in either essential hypertension or excess aldosterone production in previous studies. Because of the strong linkage disequilibrium, the observed results could be due to the action of any 1 of the 3 alleles or to another allele in linkage disequilibrium with them. Our results suggest that variations in the CYP11B2 gene may contribute to dysregulation of aldosterone synthesis and lead to susceptibility to IHA.

Alleles↗
PubMed1999

Relationship between birth weight and blood pressure in adolescence.

BACKGROUND: Several studies have found a relation ship between small size at birth and high blood pressure (HBP). However, this association has not been fully evaluated in adolescence. The aim of the present study was to evaluate the relation of birth weight (BW) to BP in adolescence, controlling for factors related to BP, to extrauterine environment, and to maternal risk of fetal distress. METHODS: In 1310 adolescents (ages 12-14 years), randomly selected from Turin school children, we evaluated BP, heart rate (HR), weight, height, familial risk of hypertension, parental cultural level, BW, and maternal history of diseases during pregnancy. The BW-BP association was tested by using multiple regression analysis and adjusting for the other variables mentioned above. The same analysis was done for the subgroup at high risk of fetal distress. RESULTS: The association between BW and BP was negative but weak when we adjusted for all confounders (= -0.07 in males; = -0.27 in females). The association was negative and became stronger after the inclusion of all confounders, particularly HR (= -3.92), in the group of children at high risk of fetal distress. CONCLUSIONS: Intrauterine environment, as reflected by BW, has little effect on BP in early adolescence without concomitant maternal diseases or environmental conditions leading to severe placental hypoperfusion.

Adolescent↗
PubMed1999

Ca2+ channels of the L-type in peripheral blood lymphocytes of essential hypertensives.

Ca2+ channels of the L-type were assayed in human peripheral blood lymphocytes of normotensive control subjects and of essential hypertensives using radioligand binding assay techniques. The dihydropyridine Ca2+ channel blocker [3H](+)-PN 200-110 [isopropyll-4-(2,1,3-benzoxadiazol-4-yl)1,4-dihydro-5-methox ycarbonyl-2,6-dimethyl-3-pyridine carboxylate] was used as a ligand. [3H](+)-PN 200 110 was bound specifically to human peripheral blood lymphocytes in a manner consistent with the labeling of Ca2+ channels of the L-type. No significant differences in the dissociation constant (Kd), in the maximum density of binding sites (Bmax) or in the pharmacological profile of [3H](+)-PN 200 110 binding were found between normotensive subjects and different degree essential hypertensives. Analysis of the intralymphocytic free Ca2+ concentration did not reveal differences between normotensive subjects and essential hypertensives. Although hypertension is associated with altered membrane handling of Ca2+, no changes in the expression of peripheral blood lymphocyte Ca2+ channels of the L-type or in intralymphocytic Ca2+ concentrations were found in essential hypertensives. Human peripheral blood lymphocytes therefore cannot represent a peripheral marker of altered Ca2+ handling in hypertension.

Adult↗
PubMed1999

Impaired baroreflex function and arterial compliance in primary aldosteronism.

The purpose of this study was to evaluate if changes in vascular properties were related to baroreflex function in patients with primary aldosteronism. Twenty-three patients with primary aldosteronism, 22 essential hypertensive patients and 16 normal controls were studied. Continuous finger blood pressure (BP) was recorded by Portapres device during supine rest and active stand up. Compliance was estimated from the time constant of pressure decay during diastole. Baroreflex sensitivity was calculated by autoregressive cross-spectral analysis of systolic BP and interbeat interval. The result was that baroreflex gain and compliance were lower in primary aldosteronism patients in the supine position (P = 0.002 and P < 0.05 respectively). Aldosterone plasma levels (R2 = 0.31, P = 0.01), age, systolic and diastolic BP, high and low frequency components of diastolic BP variability were independently related to compliance in primary aldosteronism. In conclusion primary aldosteronism is associated with an impaired baroreflex function related in part to a reduced arterial compliance. Despite a reduction of BP values and aldosterone levels, surgical or pharmacological treatment did not significantly change compliance values.

Adult↗
PubMed1999

Baroreflex control of heart rate is impaired in pre-eclampsia.

Autonomic nervous dysfunction, such as parasympathetic and sympathetic impairment, has been suggested as possible cause of pre-eclampsia, but the studies are not conclusive. Our purpose was to assess non-invasively if pre-eclampsia is associated with a decreased baroreflex function. Nine women with pre-eclampsia (PE), eight normotensive pregnant women, and seven healthy normotensive non-pregnant women were studied. Continuous finger blood pressure was recorded by a Portapres device in the left lateral recumbent position and active standing. Baroreflex gain was evaluated by cross-spectral analysis of systolic blood pressure and pulse interval. The result was that baroreflex gain at rest was lower in pre-eclamptic women both compared to non-pregnant and healthy pregnant subjects (P<0.05). Moreover, a decrease of the baroreflex sensitivity was present in all pregnant women in the orthostatic position (P<0.05). In conclusion pregnancy per se is associated with a decrease in the baroreflex control of the heart, whereas in pre-eclampsia, the baroreflex sensitivity is impaired further.

Adult↗
PubMed1999

alpha1-adrenergic receptor subtypes in human peripheral blood lymphocytes.

We investigated the expression of alpha1-adrenergic receptor subtypes in intact human peripheral blood lymphocytes using reverse transcription-polymerase chain reaction (RT-PCR) and radioligand binding assay techniques combined with antibodies against the three subtypes of alpha1-adrenergic receptors (alpha1A, alpha1B, and alpha1D). RT-PCR amplified in peripheral blood lymphocytes a 348-bp alpha1A-adrenergic receptor fragment, a 689-bp alpha1B-adrenergic receptor fragment, and a 540-bp alpha1D-adrenergic receptor fragment. Radioligand binding assay with [3H]prazosin as radioligand revealed a high-affinity binding with a dissociation constant value of 0. 65+/-0.05 nmol/L and a maximum density of binding sites of 175. 3+/-20.5 fmol/10(6) cells. The pharmacological profile of [3H]prazosin binding to human peripheral blood lymphocytes was consistent with the labeling of alpha1-adrenergic receptors. Antibodies against alpha1A-, alpha1B-, and alpha1D-receptor subtypes decreased [3H]prazosin binding to a different extent. This indicates that human peripheral blood lymphocytes express the three alpha1-adrenergic receptor subtypes. Of the three different alpha1-adrenergic receptor subtypes, the alpha1B is the most represented and the alpha1D, the least. Future studies should clarify the functional relevance of alpha1-adrenergic receptors expressed by peripheral blood lymphocytes. The identification of these sites may represent a step for evaluating whether they represent a marker of alpha1-adrenergic receptors in cardiovascular disorders or for assessing responses to drug treatment on these receptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1999

Mutations in CYP11B1 gene converting 11beta-hydroxylase into an aldosterone-producing enzyme are not present in aldosterone-producing adenomas.

In the human adrenal cortex, cortisol and aldosterone are synthesized by the isozymes 11beta-hydroxylase and aldosterone synthase, respectively, encoded by the 93% identical CYP11B1 and CYP11B2 genes. In vitro mutagenesis of CYP11B1 complementary DNA, resulting in the replacement of CYP11B1 codons by those encoding the corresponding amino acid residues of CYP11B2 enzyme (exon 5, Ser288Gly; exon 6, Val320Ala), yields a complementary DNA encoding a mutant enzyme with an efficient aldosterone synthase activity. Identical somatic mutations in the CYP11B1 gene in vivo would produce a gene encoding an enzyme with C18 activity and that would preserve ACTH responsiveness due to the retained 5'-promoter in the mutated CYP11B1 gene. An ACTH-responsive aldosterone synthase activity of this type is commonly seen in patients with aldosterone-producing adenomas (APA). We examined the occurrence of mutations in exons 5 and 6 of the CYP11B1 gene in APA from 10 patients with primary aldosteronism. Patients were selected on preoperative evidence of a 50% or greater plasma aldosterone decrease after short term dexamethasone trial and no aldosterone response to upright posture. DNA from adenomas was amplified by PCR using two pairs of primers spanning the regions of CYP11B1 gene, i.e. exons 3-5 and exons 6-9, where mutations could be located. Targeted regions were screened for mutations by automated sequencing of PCR products. No point mutations of the CYP11B1 gene over the two regions examined were found in APA. This argues against involvement of mutations in the pathogenesis of ACTH-responsive APA.

Adenoma↗
PubMed1999

Vasoactive hormones induce nitric oxide synthase mRNA expression and nitric oxide production in human endothelial cells and monocytes.

Isoform-2 nitric oxide synthase (NOS-2) mRNA expression and nitric oxide (NO) production are induced in endothelial cells and monocytes by cytokines such as gammaIFN and LPS. We evaluated NOS-2 and isoform-3 NOS (NOS-3) mRNA expression and NO production in human monocytes and human umbilical vein endothelial cells (HUVEC), under basal conditions and after incubation with physiologic concentrations of vasoactive hormones. NOS mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR) and NO production by electronic paramagnetic resonance spectroscopy (EPR). We showed that NOS-2 mRNA expression and NO production were induced by stimulation with epinephrine, dopamine, endothelin-1, and angiotensin II, both in monocytes and HUVEC. NOS-3 mRNA expression and NO production were detected under basal conditions in monocytes and HUVEC and were not modified by the presence of vasoactive hormones. Human endothelial cells and monocytes express the NOS-2 and NOS-3 mRNA and the inducible NOS-2 mRNA expression increases after vasoactive hormone stimulation.

Adult↗
PubMed1998

Blood pressure and heart rate in young thalassemia major patients.

The analysis of blood pressure (BP) and heart rate (HR) variability is currently used to investigate the mechanisms responsible for cardiovascular control; therefore, we assessed whether an impairment of 24-h BP and HR profiles and sympathovagal interaction modulating cardiovascular function was present in patients with thalassemia major (TM) in preclinical phase of heart disease. Nine beta-thalassemic patients 18 years old without clinical signs of cardiac failure and 9 age- and sex-matched controls were studied. Twenty-four-hour-ambulatory BP and HR were measured using the SpaceLabs 90207 device. A truncated Fourier series with four harmonics was used to describe the diurnal blood pressure profile. Mean 24-h ambulatory systolic BP, diastolic BP, and mean arterial pressure were significantly lower in TM patients than in normal subjects (P < .05). A significantly higher nighttime HR value was found in TM patients (P < .05). More than 40% of the TM patients did not show a significant diurnal BP and HR rhythm. In TM patients, the overall amplitude of systolic BP, diastolic BP, and HR was significantly lower than in controls (P < .01). The night/day differences of systolic BP, diastolic BP, and HR were significantly lower in TM patients than in normals (P < .01). Furthermore, we performed power spectral analysis on short-term continuous finger BP and HR data in supine position and during passive head-up tilt. Total spectral power of systolic BP was significantly lower in patients than controls (P < .05). Low-frequency (LF) power of systolic BP and diastolic BP and LF/high-frequency (HF) ratio of HR were significantly lower during tilt in TM patients compared to controls (P < .05). High-frequency power of HR was significantly higher in patients than controls (P < .05). The baroreflex gain assessed by alpha-index was the same in supine position but was higher in TM patients during passive tilt (P < .05). An inverse relationship between LF/HF ratio of HR and hemoglobin levels in TM patients was found. Finally, plasma norepinephrine levels were significantly lower in thalassemics (P < .005). In young TM patients in a preclinical stage of heart disease, these findings demonstrated abnormal 24-h BP and HR rhythms and a decreased short-term variability of BP and HR, in particular in the LF range, showing a diminished sympathetic activity.

Adolescent↗
PubMed1998

Noninvasive assessment of spontaneous baroreflex sensitivity in patients with liver cirrhosis.

AIMS/BACKGROUND: An impairment of baroreceptor sensitivity has been found in liver cirrhosis. Noninvasive and spontaneous estimates of baroreflex sensitivity are obtained from beat-to-beat blood pressure and heart rate recordings by means of cross-spectrum analysis and calculation of alpha-index (as a measure of baroreflex gain). The aim of the present study was to investigate the function of the spontaneous baroreflex sensitivity related to clinical Child score in liver cirrhosis. METHODS: The alpha-index was evaluated in 40 cirrhotic patients (18 with and 22 without ascites) and 17 healthy subjects by analysing finger arterial pressure recorded noninvasively with the Portapres device. RESULTS: Baroreflex sensitivity was significantly lower in cirrhotic patients with and without ascites compared with healthy subjects (p<0.01). Furthermore, in patients with ascites the baroreflex gain was significantly related to plasma sodium (p<0.01). A significant inverse relationship was present between baroreflex gain and grade of Child score and the severity of ascites (p<0.01). There were no significant relationships between hormonal parameters (catecholamines, renin, aldosterone, arginine-vasopressin, atrial natriuretic peptide and nitric oxide) and baroreflex gain. No significant differences were found between healthy subjects and cirrhotic patients with respect to systolic and diastolic blood pressure total variability in a supine position, whilst it was lower in cirrhotic patients with ascites in a tilted position (p<0.05). CONCLUSION: Our findings showed that baroreflex sensitivity was significantly impaired in cirrhotic patients when compared with healthy subjects. In addition, there was a significant trend toward lower baroreflex sensitivity values with the grade score of Child class (p<0.01). Spectral analysis of the alpha-index provides viable alternatives to the pharmacological approach for estimation of baroreflex sensitivity and may represent a prognostic tool to identify cirrhotic patients at increased risk of adverse events.

Aldosterone↗
PubMed1998

Evaluation of serotonin levels in human aqueous humor.

PURPOSE: Serotonin is biochemically present in the iris and ciliary body of animals and humans. Controversial findings are reported about the concentrations of serotonin in aqueous humor with respect to plasma in humans. The aim of this study was to evaluate the levels of serotonin both in aqueous humor and plasma in human subjects. METHODS: In 50 patients with glaucoma or cataract, plasma and aqueous humor serotonin levels were measured by HPLC with electrochemical detection. Serotonin plasma levels were also measured in 25 healthy subjects as controls. RESULTS: In all patients with cataract or glaucoma, the aqueous humor serotonin concentration is significantly lower than that in plasma [1.14+/-0.29 (SEM) vs. 5.33+/-1.03 ng/ml, p<0.01]. Furthermore, in the same patients and in 25 healthy controls, serotonin plasma levels were similar. CONCLUSION: Our study shows that serotonin is present in human aqueous humor and its concentration is 4 times lower than in plasma.

Adult↗
PubMed1998

Recombinant CYP11B genes encode enzymes that can catalyze conversion of 11-deoxycortisol to cortisol, 18-hydroxycortisol, and 18-oxocortisol.

CYP11B1 (11beta-hydroxylase) and CYP11B2 (aldosterone synthase) are 93% identical mitochondrial enzymes that both catalyze 11beta-hydroxylation of steroid hormones. CYP11B2 has the additional 18-hydroxylase and 18-oxidase activities required for conversion of 11-deoxycorticosterone to aldosterone. These two additional C18 conversions can be catalyzed by CYP11B1 if serine-288 and valine-320 are replaced by the corresponding CYP11B2 residues, glycine and alanine. Here we show that such a hybrid enzyme also catalyzes conversion of 11-deoxycortisol to cortisol, 18-hydroxycortisol, and 18-oxocortisol. These latter two steroids are present at elevated levels in individuals with glucocorticoid suppressible hyperaldosteronism (GSH) and some forms of primary aldosteronism. Their production by the recombinant CYP11B enzyme is enhanced by substitution of further amino acids encoded in exons 4, 5, and 6 of CYP11B2. A converted CYP11B1 gene, containing these exons from CYP11B2, would be regulated like CYP11B1, yet encode an enzyme with the activities of CYP11B2, thus causing GSH or essential hypertension. In a sample of 103 low renin hypertensive patients, 218 patients with primary aldosteronism, and 90 normotensive individuals, we found a high level of conversion of CYP11B genes and four cases of GSH caused by unequal crossing over but no gene conversions of the type expected to cause GSH.

Case-Control Studies↗
PubMed1998

Diagnosis of glucocorticoid-remediable aldosteronism in primary aldosteronism: aldosterone response to dexamethasone and long polymerase chain reaction for chimeric gene.

Aldosterone suppression by dexamethasone, and high 18-hydroxycortisol and 18-oxocortisol levels are used to differentiate glucocorticoid-remediable aldosteronism (GRA) from other forms of primary aldosteronism. These methods are time consuming, expensive, and impractical for large studies. Moreover, diagnosis of GRA requires a confirmatory genetic test. We evaluated 117 patients with primary aldosteronism referred to our centers by the use of a long PCR technique to reveal the chimeric gene of GRA. In 60 of 117 patients, the response of aldosterone to dexamethasone (2 mg/day for 4 days) was also assessed. None of our patients, including 2 pairs of siblings, was positive for the chimeric gene. The results of long PCR were confirmed by Southern blotting. Despite a negative genetic test, 6 patients (1 with aldosterone-producing adenoma and 5 with idiopathic hyperaldosteronism) had plasma aldosterone suppressed by dexamethasone (i.e. < or = 2 ng/dL). Of 117 patients, 43 were identified as having aldosterone-producing adenoma and 74 as having idiopathic hyperaldosteronism. In our experience, the long PCR technique is a reliable and simple test to at least exclude GRA in patients with primary aldosteronism. A short term dexamethasone suppression test of aldosterone can be misleading in identifying GRA. The prevalence of GRA in primary aldosteronism remains to be established.

Adult↗
PubMed1997

Fourier analysis of circadian blood pressure profile in secondary hypertension.

Different types of statistical methods have been used for circadian blood pressure (BP) rhythm analysis in secondary forms of hypertension. In the present study, we used the two-step statistical approach by Fourier analysis with four harmonics for the parametrization of the diurnal BP pattern in secondary hypertension. In 43 essential hypertensives (EH), eight patients with aldosterone producing adenoma (APA), 25 with idiopathic hyperaldosteronism (IHA), four with glucocorticoid remediable hyperaldosteronism (GRH) and seven with renovascular hypertension (RVH), 24-h ambulatory BP was measured. The diurnal BP and heart rate (HR) rhythm was present in more than 70% of patients with secondary hypertension, without significant differences with EH and despite the attenuation in the degree of the nocturnal BP fall. In conclusion, the statement that secondary hypertension is characterized by an abnormal diurnal rhythm of BP is a gross over-simplification. Our findings suggest that the two-step method with four harmonics Fourier analysis may represent a useful method and a more complete statistical approach to providing circadian parametrization of the 24-h profile in secondary hypertension.

Blood Pressure↗