Biomedical subjects

G Desideri

Publications and source records attributed to G Desideri.

29 records · Page 2Linked to original sources

PubMed1997

Elevated albumin excretion in nonmodulating essential hypertensive patients.

Nonmodulating (NM) essential hypertensives are characterized by abnormal renal and aldosterone responses to angiotensin II. Recently, hyperinsulinemia, hypercholesterolemia, and an increased prevalence of family history of hypertension and myocardial infarction have been shown in NM hypertensives. Since an elevated urinary albumin excretion (UAE) has been indicated as a negative prognostic marker for cardiovascular diseases in essential hypertensives, we evaluated UAE in 50 male patients with mild to moderate essential hypertension (mean age 46.3 +/- 4.4 years), characterized as low renin (LR) (n = 14), modulating (M) (n = 20), and NM patients (n = 16) according to their renin profile and ability to modulate the aldosterone response to a graded infusion of angiotensin II. A group of 14 healthy male subjects (mean age 43.3 +/- 3.9 years) served as control. Resulting data showed that NM had significantly higher UAE (30.7 +/- 10.7 microg/min) than controls (11.9 +/- 2.7 microg/min, p < 0.0001), LR (22.1 +/- 8.4 microg/min, p < 0.05), and M patients (19.7 +/- 6.6 microg/min, p = 0.0001) when all fed a 200-mmol NaCl/day diet. On the contrary, differences in UAE disappeared when all subjects were on a low sodium regimen (10 mmol NaCl/day). Compared to LR and M patients, the NM ones also manifested higher low-density lipoprotein cholesterol levels (p < 0.05). Furthermore, these latter and UAE were positively correlated in NM patients (r = 0.579, p < 0.05) but not in the other subgroups. In conclusion, the current study demonstrates elevated UAE in NM patients, suggesting the NM phenotype is combined to an increased cardiovascular risk.

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PubMed1997

Effects of ACE inhibition on spontaneous and insulin-stimulated endothelin-1 secretion: in vitro and in vivo studies.

To evaluate the effect of angiotensin-converting enzyme inhibition on spontaneous and insulin-stimulated endothelin-1 (ET-1) secretion in vitro and in vivo, human endothelial cells derived from umbilical cord veins were cultured onto acellular collagen-coated permeable membrane, thus mimicking in vivo conditions with a luminal and abluminal side. Insulin (10(-6,-8,-9) mol/l) significantly stimulated ET-1 secretion by cultured cells (P < 0.05 starting from 2-h incubation). Captopril (10(-7,-8,-9) mol/l) significantly reduced both spontaneous and insulin-stimulated ET-1 secretion, while increasing nitric oxide production. Considering each cell side, captopril significantly inhibited the apical secretion of ET-1, while its effect on the basolateral compartment was modest. In the presence of D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin (10(-6) mol/l), a bradykinin B2 receptor antagonist, captopril had no effects on ET-1 and nitric oxide production and also when insulin was added to the culture media. With regard to in vivo experiments, oral captopril therapy (25 mg twice daily for 1 week) was given to normotensive (n = 5) and hypertensive (n = 6) subjects and significantly decreased plasma ET-1 concentration (normotensive subjects, before: 0.98 +/- 0.09 pg/ml; after: 0.55 +/- 0.08 pg/ml, P < 0.0001; hypertensive subjects, before: 1.05 +/- 0.03 pg/ml; after: 0.56 +/- 0.05 pg/ml, P < 0.0001). Transient hyperinsulinemia was accompanied by a significant rise in plasma ET-1 concentrations in both groups (P < 0.0001 at 180 and 210 min) before but not after captopril treatment. In conclusion, captopril inhibits both spontaneous and insulin-stimulated ET-1 secretion by endothelial cells, acting on angiotensin-converting enzyme bound to the luminal cell side. In vivo, captopril significantly reduces plasma ET-1 levels in both basal and insulin-stimulated conditions.

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PubMed1996

Impaired inactive to active kallikrein conversion in human salt-sensitive hypertension.

Active and inactive urinary kallikrein excretion rates were evaluated in 43 essential hypertensive men (45.4 +/- 5.6 yr) after normal-(120 mmol/day), low-(20 mmol/day), and high-(240 mmol/day) NaCl diets were given for 2 wk each. Patients were classified as salt-sensitive, salt-resistant, or counterregulating, on the basis of their blood pressure responses to the different NaCl intakes. Resulting data show that active and inactive kallikrein excretion rates were lower (P < 0.001) in salt-sensitive (active, 0.59 +/- 0.27 U/24 h; inactive, 3.45 +/- 1.31 U/24 h) than in salt-resistant (active, 1.41 +/- 0.35 U/24 h; inactive, 6.93 +/- 2.68 U/24 h) and in counterregulating hypertensive patients (active, 1.37 +/- 0.39 U/24 h; inactive, 6.32 +/- 2.58 U/24 h) after the normal NaCl diet. Salt-sensitive hypertensive patients showed also higher plasma digoxin-like substance (P < 0.001), atrial natriuretic peptide (P < 0.001), and fasting insulin (P < 0.005) levels than the other subgroups. Active kallikrein decreased after high and increased after low-NaCl intake in all groups. Inactive kallikrein varied similarly to active one in salt-resistant patients and counterregulating patients, whereas it increased during salt-loading in salt-sensitive patients. Consequently, the active/total kallikrein ratio decreased in salt-sensitive patients (from 20.2 +/- 3.5 to 5.82 +/- 1.02%, P < 0.05) when they switched from low- to high-NaCl intake, and the ratio was lower in these patients than in the other subgroups (P < 0.0001) after the high-NaCl diet. In conclusion, active and inactive kallikrein excretions after normal-NaCl intake are reduced in salt-sensitive hypertensive patients. The divergent active and inactive kallikrein responses to dietary NaCl changes in salt-sensitive patients could indicate an impairment of inactive to active kallikrein conversion during NaCl loading as a new mechanism in human salt-sensitive hypertension.

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PubMed1996

Active kallikrein response to changes in sodium-chloride intake in essential hypertensive patients.

To evaluate the behavior of active kallikrein excretion in salt-sensitive and salt-resistant hypertensive patients during changes in sodium-chloride (NaCl) intake, 61 male, nonobese, nondiabetic outpatients affected by uncomplicated essential hypertension were given a diet that contained 140 mmol NaCl per day for 2 wk. Patients then received either a low- (20 mmol NaCl/day) or a high- (320 mmol NaCl/day) sodium diet for 2 wk, according to a randomized, double-blind, cross-over protocol. Hypertensive patients were classified as salt sensitive when their diastolic blood pressure rose by at least 10 mm Hg after the high-sodium diet, and decreased by at least 10 mm Hg after the low-sodium diet, considering as baseline blood pressure values those that were taken at the end of the 140 mmol NaCl/day intake period. The remaining patients were classified as salt resistant or, when diastolic blood pressure increased by 10 mm Hg or more after low-sodium intake, as counter-regulating. Twenty-three patients were therefore classified as salt sensitive, 28 as salt resistant, and 10 as counter-regulating. The baseline active kallikrein excretion was significantly lower (P < 0.0001) in salt-sensitive (0.62 +/- 0.31 U/24 h) patients than in salt-resistant (1.39 +/- 0.44 U/24 h) and counter-regulating patients (1.27 +/- 0.38 U/24 h). Surprisingly, the kallikrein response to changes in sodium intake was similar in all subgroups, although enzyme excretion was always at the lowest level in salt-sensitive hypertensive patients. This latter group also showed the highest plasma atrial natriuretic peptide levels (28.2 +/- 8.5 fmol/mL, P < 0.0001 versus salt-resistant and counter-regulating patients), and the greatest peptide increment with sodium load (P < 0.0001 versus salt-resistant and counter-regulating patients). Counter-regulating patients showed the steepest increase in plasma renin activity (from 0.24 +/- 0.18 to 0.83 +/- 0.21 ng/L per s, P < 0.001) and decrease of plasma atrial natriuretic peptide (from 26.1 +/- 6.3 to 6.8 +/- 3.1 fmol/mL, P < 0.001) when switched from a high to a low-sodium intake. In conclusion, salt-sensitive hypertensive patients excrete less active kallikrein than do salt-resistant and counter-regulating patients, but maintain a normal enzyme response to changes in dietary sodium intake. The exaggerated response of atrial natriuretic peptide to high-sodium intake that was observed in the same patients could be compensating for an impaired renal capability to excrete a sodium load.

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PubMed1996

Endogenous insulin modulates circulating endothelin-1 concentrations in humans.

OBJECTIVE: To assess the effect of oral glucose loading on plasma endothelin-1 (ET-1) levels in humans. RESEARCH DESIGN AND METHODS: A total of 75 g D-glucose was given orally to 14 nonobese nondiabetic essential hypertensive subjects (eight men and six women, mean age 43.1 +/- 3.0 years) and eight normotensive subjects (four men and four women, mean age 45.2 +/- 4.1 years). Blood samples for plasma ET-1 measurement were drawn every 30 min for 2 h and then at 180 and 240 min. RESULTS: After glucose load, insulin increased more significantly in hypertensive subjects than in normotensive subjects at times 60 (P = 0.004) and 90 (P = 0.001) min. Glucose loading was followed by a mild but significant increase in circulating ET-1 levels in both groups (hypertensive subjects, from 0.87 +/- 0.25 pg/ml at time 0 to 1.64 +/- 0.33 pg/ml at 120 min and 1.74 +/- 0.38 pg/ml at 180 min, P < 0.05; normotensive subjects, from 0.82 +/- 0.38 pg/ml at time 0 to 1.42 +/- 0.18 pg/ml at 180 min, P < 0.05). Whereas baseline ET-1 levels were similar between the two groups, postload ET-1 levels were higher in hypertensive subjects than in normotensive subjects (P = 0.003 at 120 min; P = 0.04 at 180 min). CONCLUSIONS: This study indicates that significant changes in circulating ET-1 levels occur after oral glucose loading, probably due to a glucose-induced increment in endogenous insulin concentration.

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PubMed1996

Plasma and urinary digitalis-like substance levels during atrial natriuretic peptide infusion in essential hypertensive patients.

In order to evaluate the effect of atrial natriuretic peptide (ANP) infusion on plasma and urinary digitalis-like substance (DLS) levels, 18 essential hypertensive males (mean age 45.6 +/- 3.8 y) were studied. After 1 week on a normal NaCl intake (120 mmol/24h), patients were randomly double-blindly assigned to receive either ANP (99-126) (0.3 microgram/kg/min) (number of patients = 10) or its vehicle (50 ml isotonic saline) (8 patients) over a period of 60 min, in supine position. Plasma and urinary DLS levels were measured at time -60, 0, 30, 60, 120, 180, and 240 min (infusion time from 0-60 min). During ANP infusion, plasma DLS levels decreased significantly (from 25.2 +/- 6.8 pg/ml at time 0 to 12.5 +/- 5.6 pg/ml at 60 min, p < 0.01), while urinary DLS excretion increased (from 60.5 +/- 26.1 pg/ml at time 0 to 246.3 +/- 34.2 pg/ml at 30 min, p < 0.0001). and 402.3 +/- 44.1 pg/ml at 60 min, p < 0.0001). After 3 h from the end of ANP infusion, both plasma and urinary DLS returned to baseline levels (20.5 +/- 14.4 pg/ml and 84.5 +/- 34.2 pg/ml, respectively). Taken together, our data show that ANP infusion significantly increases urinary DLS excretion, while decreasing its circulating levels. This phenomenon could explain the different response of ANP and DLS to some stimuli, such as acute volume expansion. In fact, the rapid increment of plasma ANP due to an acute increase of extracellular fluid volume might simultaneously inhibit the increase in circulating DLS levels by promoting the urinary excretion of this substance.

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PubMed1996

[Endothelial dysfunction in salt sensitive hypertension].

Plasma endothelin-1 (ET-1) and von Willebrand factor (vWF) levels are elevated in the presence of either macro- or microvascular lesions. Since an increased risk to develop hypertension-related vascular damage has been suggested in human sensitive hypertension, we evaluated both substances in plasma samples from 20 non-diabetic, non obese essential hypertensive men (mean age 49 +/- 4 years). Patients were divided in salt sensitive (n = 9) or salt resistant (n = 11) groups, according to the individual response to both high- and low-sodium diets. Plasma ET-1 levels were also assessed after an oral glucose tolerance test (75 g). Both ET-1 and vWF were higher in salt sensitive than salt resistant patients (ET-1 p < 0.01; vWF p < 0.03). Furthermore, after oral glucose administration, plasma ET-1 concentrations increased very mildly but significantly only in salt sensitive patients (p < 0.05 at 90 min). In conclusion, human salt sensitive hypertension is combined to increased levels of two markers of endothelial damage, and by an augmented ET-1 response to glucose leading, suggesting it is characterized by an increased risk to develop hypertension-related vascular complications.

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PubMed1995

Plasma endothelin-1 levels in obese hypertensive and normotensive men.

Plasma endothelin-1 (ET-1) levels were studied in 15 obese hypertensive (mean age 48.5 +/- 3.9 years) and 15 obese normotensive men (mean age 49.5 +/- 3.6 years) before and after weight loss due to an 800 kcal/day diet lasting 12 weeks. Circulating peptide concentrations were also assessed in nonobese hypertensive (n = 11) and normotensive men (n = 12). Baseline plasma ET-1 levels were similar in obese hypertensive (0.87 +/- 0.22 pg/ml) and obese normotensive men (0.91 +/- 0.30 pg/ml). In seven obese hypertensive men, caloric restriction normalized blood pressure levels (systolic: from 166.6 +/- 8.1 to 145.0 +/- 6.3 mmHg, P < 0.0001; diastolic: from 106.6 +/- 5.1 to 89.1 +/- 2.0 mmHg, P < 0.0001) and decreased body mass index (BMI) (from 33.4 +/- 1.6 to 29.6 +/- 2.1 kg/m2, P < 0.002) and plasma ET-1 levels (from 0.93 +/- 0.21 to 0.64 +/- 0.26 pg/ml, P < 0.05). In the remaining obese hypertensive men (n = 8), blood pressure levels were not normalized by caloric restriction despite a significant decrease of BMI and plasma ET-1 levels (from 0.83 +/- 0.23 to 0.60 +/- 0.16 pg/ml, P < 0.04). Weight loss also significantly decreased BMI and ET-1 (from 0.91 +/- 0.30 to 0.65 +/- 0.19 pg/ml, P < 0.01) in obese normotensive men. Baseline ET-1 and fasting insulin levels were significantly correlated in obese hypertensive (r = 0.518, P < 0.05) and obese normotensive men (r = 0.535, P < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1994

Salt-sensitivity is associated with a hyperinsulinaemic and hyperglycaemic response to atrial natriuretic peptide infusion in human essential hypertension.

To evaluate the influence of salt-sensitivity on the plasma insulin and glucose response to infusion of ANP, we studied 22 men with essential hypertension, who were between 40 and 60 years old. After 1 month under normal Na+ intake (120 mmol Na+ per day), patients were randomly assigned to receive either ANP (0.04 micrograms.kg-1.min-1) (n = 15) or vehicle (50 ml saline) (n = 7) over a 60-min period, while in the supine position. Plasma insulin and glucose were measured at time -60, 0, 20, 40, 60, 120, 180, 240 min. Ten days after ANP infusion, blood pressure sensitivity to changes in dietary salt intake was assessed according to a randomized double-blind crossover protocol. Patients were classified into two groups either salt-sensitive (n = 8) or salt-resistant (n = 7). Our results showed that plasma insulin and glucose did not change during ANP infusion in both groups. However, both plasma insulin (from 75.6 +/- 45.1 pmol/l at 60 min to 121.2 +2- 48.6 pmol/l at 240 min, p < 0.05 vs time 0) and glucose levels (from 4.86 +/- 0.73 mmol/l at 60 min to 6.56 +/- 1.03 mmol/l at 240 min, p < 0.01 vs time 0) rose after discontinuation of ANP in salt-sensitive patients, but did not change at all in salt-resistant patients. In conclusion, this randomized vehicle-controlled study demonstrates that plasma insulin and glucose levels increase in salt-sensitive hypertensive patients after the infusion of ANP. The increase of plasma insulin levels observed after ANP discontinuation, if occurring under physiologic conditions, could influence the blood pressure sensitivity to dietary Na+ intake.

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PubMed1993

Effects of short-time insulin suppression on renal sodium excretion in type II diabetic hypertensives.

The effects of a short-time insulin suppression on Na+ excretion were evaluated in 9 type II diabetic hypertensive males. All patients had a body mass index < 26 and normal plasma lipid levels. After 2 weeks under constant NaCl intake (120 mEq of NaCl daily) either octreotide, a somatostatin analogue, or its vehicle were infused in a forearm vein during acute volume expansion (0.20 ml/kg/min isotonic saline given intravenously over a period of 30 min). A double blind randomized cross-over design was followed, and each patient was given both infusions at one week interval. Blood and urine samples for the evaluation of plasma insulin and serum and urine Na+ were taken at time-30, 0, 30, 60, 90, 120, and 240 min. Our data showed that octreotide completely suppressed insulin levels (from time 0 to 60 min). During acute volume expansion+octreotide, Na+ excretion was 0.20 +/- 0.15 mEq/min at time 0, 0.23 +/- 0.21 mEq/min at time 30, 0.64 +/- 0.24 mEq/min at 60 (p < 0.05 vs time 0), 0.71 +/- 0.35 mEq/min at 90 (p < 0.05 vs time 0), 0.78 +/- 0.10 mEq/min at 120 (p < 0.01 vs time 0) and 0.71 +/- 0.12 mEq/min at 240 min (p < 0.05 vs time 0). As compared to acute volume expansion alone, octreotide induced a significant increase of Na+ excretion at 60 and 90 min (p < 0.05). In conclusion, a short-time insulin suppression, as obtained by the somatostatin analogue octreotide, enhances the natriuretic response to intravenous saline load in lean type II diabetic hypertensives.

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PubMedDate not supplied

[Sodium-modulating hormones and the pressor response to sodium chloride in essential arterial hypertension].

Some predictive markers for NaCl sensitivity, related to the red blood cell membrane or to circulating proteins, have already been described in human essential hypertension. The present study was planned to investigate whether or not some hormones produced by the kidney or acting at the kidney level could be used as new markers for NaCl sensitivity. The study was conducted in 28 not previously treated outpatients affected by uncomplicated mild to moderate essential hypertension. After 15 days on a normal NaCl diet, plasma renin activity (PRA), plasma atrial natriuretic peptide (ANP), and the urinary excretion of active kallikrein were evaluated. The sensitivity of blood pressure to changes in NaCl intake was then assessed in all patients, according to a randomized double blind cross-over design. Each patient was assigned to a high (240 mmol of NaCl/day for 15 days) or low (40 mmol of NaCl/day for 15 days) NaCl intake. During the assessment of NaCl sensitivity, the double blindness was achieved by the use of capsules containing either NaCl or placebo. Fifteen patients (11 males and 4 females) resulted as NaCl-sensitive, while 13 patients (8 males and 5 females) were classified as NaCl-resistant. Our results indicate that PRA levels were significantly lower in the NaCl-sensitive group than in the NaCl-resistant one (0.108 +/- 0.05 ng/L/s vs 0.247 +/- 0.16 ng/L/s, p < 0.007), in the presence of raised levels of plasma ANP in NaCl-sensitive hypertensives (18.08 +/- 4.61 fmol/mL vs 12.45 +/- 3.77 fmol/mL, p < 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

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