PubMed Health⌕ Search

Biomedical subjects

G Del Rio

Publications and source records attributed to G Del Rio.

At least 19 recordsLinked to original sources
PubMed2002

Weight gain in women with breast cancer treated with adjuvant cyclophosphomide, methotrexate and 5-fluorouracil. Analysis of resting energy expenditure and body composition.

BACKGROUND: Weight gain is a common side effect observed in women undergoing adjuvant chemotherapy for breast cancer. Among possible causes a direct effect of chemotherapy on metabolism has been proposed. Body composition variations after adjuvant chemotherapy suggest the occurrence of sarcopenic obesity, possibly due to ovarian failure. We investigated acute and chronic effects of adjuvant chemotherapy on body weight, resting energy expenditure (REE) and plasma catecholamines in a group of menopausal women. PATIENTS AND METHODS: Thirty menopausal women with stage I-II breast cancer were recruited for the study. We measured REE and respiratory quotient (RQ) and body composition at the beginning and after 3 and 6 months of adjuvant cyclophosphomide, methotrexate, and 5-fluorouracil (CMF). REE, RQ, and plasma catecholamines were assessed before and after each chemotherapy session. At each session food intake was also assessed in all patients, by a food diary. Seven patients out of the group of 30 were also evaluated after a placebo infusion (saline). RESULTS: A significant weight gain was observed in all women (70.5 +/- 3 v.s. 67.7 +/- 3 kg, p < 0.001), with increase in both fat-free mass (FFM) (45.2 +/- 1.5 v.s. 43.6 +/- 1.3 kg, p < 0.001) and fat-mass (FM) (25.3 +/- 1.7 v.s. 24.1 +/- 1.8 kg, p < 0.005). A decrease in REE and RQ was observed both during CMF and placebo infusion (p < 0.05). During acute CMF and placebo infusion a reduction of plasma levels of noradrenaline was observed at the first and last session. REE increased progressively during the study period. CONCLUSIONS: CMF therapy apparently has no effect on REE either acutely or during a 6-month-period; the increased REE observed in the long-term is likely due to the concomitant increase in FFM. The lack of evidence of sarcopenic obesity, at variance with previous literature, is likely due to different patient selection.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

A ligand-receptor pair that triggers a non-apoptotic form of programmed cell death.

Several receptors that mediate apoptosis have been identified, such as Fas and tumor necrosis factor receptor I. Studies of the signal transduction pathways utilized by these receptors have played an important role in the understanding of apoptosis. Here we report the first ligand-receptor pair-the neuropeptide substance P and its receptor, neurokinin-1 receptor (NK(1)R)-that mediates an alternative, non-apoptotic form of programmed cell death. This pair is widely distributed in the central and peripheral nervous systems, and has been implicated in pain mediation and depression, among other effects. Here we demonstrate that substance P induces a non-apoptotic form of programmed cell death in hippocampal, striatal, and cortical neurons. This cell death requires gene expression, displays a non-apoptotic morphology, and is independent of caspase activation. The same form of cell death is induced by substance P in NK(1)R-transfected human embryonic kidney cells. These results argue that NK(1)R activates a death pathway different than apoptosis, and provide a signal transduction system by which to study an alternative, non-apoptotic cell death program.

Animals↗
PubMed2000

The effects of transdermal estradiol on the response to mental stress in postmenopausal women: a randomized trial.

PURPOSE: Estrogens inhibit adrenomedullary catecholamine release and catecholamine-mediated responses to stress. We examined whether estrogen supplementation reduces the sympathoadrenal response to mental stress in postmenopausal women. MATERIALS AND METHODS: We compared the effects of 3-week treatment with transdermal 17-beta-estradiol and placebo in 10 postmenopausal women using a randomized, blinded, crossover design. We measured plasma catecholamine levels and the cardiovascular and metabolic responses to a 15-minute stress with mental arithmetic. Treatments were compared using repeated measures analysis of variance. RESULTS: During placebo treatment, mean (+/- SD) epinephrine levels reached a peak of 431 +/- 135 pmol/liter after 15 minutes of stress; the epinephrine response was blunted during estradiol treatment, with a peak of 357 +/- 77 pmol/liter (P <0.05). Estradiol also blunted the diastolic blood pressure response to stress (baseline levels of 78 +/- 15 mm Hg vs peak of 90 +/- 6 mm Hg during placebo; baseline of 80 +/- 8 mm Hg vs peak of 84 +/- 6 mm Hg during estradiol; P <0.05). Estradiol treatment also blunted the decrease in the standard deviation of the mean of the electrocardiographic RR intervals and the increase in the ratio between the low-frequency and high-frequency bandwidths. CONCLUSION: We observed a moderate, although significant, reduction in markers of the stress response to mental arithmetic in postmenopausal women treated with transdermal 17-beta-estradiol.

Administration, Cutaneous↗
PubMed2000

Sympathoadrenal response of postmenopausal women prior and during prolonged administration of estradiol.

OBJECTIVE: Cardiovascular disease seems to increase after the menopause and is thought to be reduced by estrogen replacement therapy. Among the many studies which have tried to define the multifactorial mechanisms of estrogens cardiovascular prevention, very few have focused on their possible modulation of adrenergic activity. In the present study we investigated whether prolonged estradiol replacement via transdermal patches is able to modulate cardiovascular and adrenergic responses to stimuli. METHODS: Baseline and responses to a cold stimulus and to the upright position of catecholamines (epinephrine and norepinephrine), heart rate, systolic and diastolic blood pressure were investigated in 15 healthy volunteer postmenopausal women both prior to and after 2 months of treatment with patches rated to deliver 50 microg/day of estradiol. RESULTS: Basal norepinephrine levels (P<0.005), as well as their integrated responses to the cold stimulus (P<0.02) were lower during estradiol. By contrast, responses of norepinephrine to the upright test, as well as basal and responses to stimuli of epinephrine and circulatory parameters were not different before and during estradiol. CONCLUSIONS: Estradiol replacement at low doses significantly decreases overall sympathetic output, both in basal conditions and under specific stimuli. These effects whether maintained or magnified in the long term may play a role in the prevention of the postmenopausal cardiovascular risk.

Administration, Cutaneous↗
PubMed2000

Metabolic effects of fluoxetine in obese menopausal women.

Our objective was to assess thermogenic action of fluoxetine (FL) in obese menopausal women, evaluating the effect of FL administration on resting energy expenditure (REE) and on glucose-induced thermogenesis both after acute administration (40 mg in single dose the evening before measurements) and after a 12- week period of diet treatment plus FL (60 mg per day) or placebo. It was a double-blind, placebo-controlled design both in acute and in chronic study. The subjects were 32 obese, otherwise healthy, menopausal women. The patients were assigned randomly to three groups, one performing an acute study protocol, in which resting and glucose-induced thermogenesis was measured after FL and placebo administration, performed in randomised order. The other two groups underwent dietary plus pharmacological treatment (FL or placebo, PL). Resting and glucose-induced thermogenesis was measured at baseline and after 12 weeks of treatment. The results showed that acute FL administration caused an increase in resting energy expenditure (PL: 5.35+/-0.18 vs FL: 5.53+/-0.24 KJ/min, p<0.05). A significant decrease of REE was observed in the PL group after 12 weeks (p<0.03), while a slight, but not significant, decrease was observed in the FL group (p=NS). FL did not affect thermic response to oral glucose neither after acute nor chronic administration (p=NS for all groups studied). The conclusion was that our data give support to thermogenic actions of FL after acute administration, suggesting also that chronic FL treatment may restrain to some degree the metabolic adaptation expected during weight loss in obese subjects. At variance with what observed with other drugs, such as dexfenfluramine, an increased thermic effect of oral glucose does not seem to be involved in the thermogenetic action of FL.

Antidepressive Agents, Second-Generation↗
PubMed2000

Adrenomedullary function and its regulation in obesity.

Sympathoadrenal system (SAS) represents a major contributor to body homeostasis, regulating blood pressure heart rate, energy balance and intermediary metabolism. Thus, it is not unexpected that in last decades a consistent literature has been focused on the possible role of sympathoadrenal system in the pathogenesis of human obesity. There are, however, many factors confounding comparison of sympathoadrenal system activity between lean and obese subjects. Among these, one should be aware that SAS should be functionally separated into sympathetic nervous system (SNS) and adrenal medulla (AM), and that each of these two systems can be activated independently from the other by distinct physiological stimuli; this phenomenon in fact underlies the discordant pattern of findings for adrenomedullary and sympathetic activity in human obesity. While, in fact, obese subjects often display an increased basal SNS activity, there are numerous reports of blunted AM function in obese. Recent evidence suggests that this reduced adrenaline secretion is an acquired feature of human obesity, a finding that fits in well with the hypothesis that hormonal milieu, particularly sex steroids and cortisol, plays a role in the determination of blunted AM activity. Catecholamines have been recently demonstrated to play a role also in the regulation of whole energy balance. Adrenaline in fact acutely reduces both leptin mRNA as well as circulating leptin in human obese subjects, suggesting that catecholamines may influence the cross-talk between energy stores and the centrally mediated modulation of food intake. In summary, the study of adrenomedullary function and of possible mechanisms of its disturbances in human obesity, appears of great interest, and surely deserves further investigations.

Adrenal Medulla↗
PubMed2000

Resting metabolic rate, fat-free mass and catecholamine excretion during weight loss in female obese patients.

The reduction in resting metabolic rate (RMR) during weight loss exceeds that accounted for by changes in body composition by 15%, suggesting that factors other than fat-free mass (FFM) explain the metabolic adaptation during food restriction in obesity. Our study aimed to establish if changes in the sympathoadrenal system activity, as inferred from an integrated measure such as 24 h urinary excretion of catecholamines, may play a role in the RMR adaptation observed during dietary restriction in obese patients. Ninety-three obese female subjects consumed a low-energy diet (LED) (2930 kJ/d (700 kcal/d)) for a 3-week period. At the beginning and at the end of the study, 24 h urinary excretion of catecholamines, FFM and RMR were measured. The LED induced a significant reduction in body weight (-3.3 (SEM 0.4) kg; P < 0.01), FFM (-1.9 (SEM 0.7) kg; P < 0.01) and in the fat mass (-1.2 (SEM 0.5) kg; P < 0.01). Noradrenalin excretion (24 h) decreased during the LED from 264 (SEM 26) during a weight-maintenance period to 171 (SEM 19) nmol/24 h after consumption of the LED for 3 weeks (P < 0.001); mean 24 h adrenalin excretion did not change during the LED (22 (SEM 3) during the weight-maintenance period v. 21 (SEM 3) nmol/24 h after consumption of the LED for 3 weeks; NS). The LED induced a significant decrease in RMR (7300 (SEM 218) v. 6831 (SEM 138) kJ/24 h; P < 0.001). The only independent variable that significantly explained variations in RMR both before and after consumption of the LED for 3 weeks, was FFM (r2 0.79 and r2 0.80 respectively). Urinary noradrenalin excretion explained a further 4% of the variability in RMR, but only before the diet, so that a role of sympathoadrenal system on RMR seems to be present in obese patients in basal conditions but not at the end of the LED.

Adolescent↗
PubMed1999

Cardiac effects of hexarelin in hypopituitary adults.

Growth hormone (GH)-releasing peptides possess specific pituitary, hypothalamic, and myocardial receptors. Seven adult male patients with GH deficiency (GHD) (age, mean+/-S.E.M.: 42.0+/-4.0 year) were studied by equilibrium radionuclide angiocardiography after i.v. administration of hexarelin, a peptide GH secretagogue. Data for these patients were compared with those for nine adult male controls (37.0+/-2.7 year). The GH response to hexarelin was negligible in patients with GHD compared to control subjects (CS) (peak: 1.9+/-0.9 vs. 45.7+/-3.6 microg/l, P<0.001). Basal left ventricular ejection fraction (LVEF) in patients with GHD was lower than that in CS (50+/-1% vs. 63+/-2%, P<0.001). Hexarelin administration increased LVEF both in patients with GHD and in CS (peak: 57+/-2 vs. 70+/-2, respectively, P<0.05 vs. baseline) without changing catecholamine levels, mean blood pressure (MBP), or cardiac output in either group. In conclusion, the acute administration of hexarelin exerts a short-lasting positive inotropic effect in humans, probably GH-independent and mediated by specific myocardial receptors for GH secretagogues.

Adult↗
PubMed1999

Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans.

Reduced cardiac mass and performances are present in GH deficiency and are counteracted by rhGH replacement. GH and IGF-I possess specific myocardial receptors and have been reported able to exert an acute inotropic effect. Synthetic GH secretagogues (GHS) possess specific pituitary and hypothalamic but even myocardial receptors. In 7 male volunteers, we studied cardiac performance by radionuclide angiocardiography after iv administration of rhGH or hexarelin (HEX), a peptidyl GHS. The administration of rhGH or HEX increased circulating GH levels to the same extent (AUC: 1594.6+/-88.1 vs 1739.3+/-262.2 microg/l/min for 90 min) while aldosterone and catecholamine levels did not change; HEX, but not rhGH, significantly increased cortisol levels. Left ventricular ejection fraction (LVEF), mean blood pressure (MBP) and heart rate (HR) were unaffected by rhGH (62.4+/-2.1 vs 62.1+/-2.3%, 90.6+/-3.4 vs 92.0+/-2.5 mm Hg, 62.3+/-1.8 vs 66.7+/-2.7 bpm). HEX increased LVEF (70.7+/-3.0 vs 64.0+/-1.5%, p<0.03) without significant changes in MBP and HR (92.8+/-4.7 vs 92.4+/-3.2 mm Hg, 63.1+/-2.1 vs 67.0+/-2.9 bpm). LVEF significantly raised at 15 min, peaked at 30 min and lasted up to 60 min after HEX. These findings suggest that in man, the acute administration of Hexarelin exerts a short-lasting, positive inotropic effect. This effect seems GH-independent and might be mediated by specific GHS myocardial receptors.

Adult↗
PubMed1999

GH/IGF-I axis in azoospermia in primary and secondary hypogonadism: a study before and during replacement therapy.

The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis was studied in 15 azoospermic patients and in 10 control men. Eight patients were affected by hypergonadotrophic hypogonadism and 7 by hypogonadotrophic hypogonadism. All were studied before and during replacement therapy with testosterone and gonadotrophin, respectively, using the alpha 2 adrenergic agonist, clonidine (clonidine test). The data demonstrate no differences in basal levels for IGF-I and for the GH response to clonidine in azoospermic patients, affected by primary and secondary hypogonadism, before and during replacement therapy when compared with control fertile men. In contrast to some studies which describe a reduced GH response in azoospermia and oligozoospermia, we conclude that basal serum levels of IGF-I and the GH response to clonidine are not impaired in azoospermic patients affected by primary hypogonadism before and after the restoration of normal androgenization, and in azoospermic patients affected by secondary hypogonadism, both before and after restoration of spermatogenesis.

Adolescent↗
PubMed1999

Regulation of ob gene expression: evidence for epinephrine-induced suppression in human obesity.

Leptin acts as satiety factor and increases energy expenditure. Studies conducted on animals and in vitro on adipocytes culture have shown that infusion of catecholamines leads to a significant reduction of ob gene expression; it appears of interest to evaluate the in vivo effects of adrenergic activation on the expression of the ob gene in humans. We studied ob gene expression in adipose tissue samples from 13 obese subjects before and after epinephrine (25 ng/min x kg ideal body weight for 3 h) and 6 obese patients during saline infusion. Hormonal infusion led to a significant increase in epinephrine plasma levels (from 27 +/- 4 to 339 +/- 75 pg/mL; P < 0.001), plasma free fatty acids (from 0.73 +/- 0.05 to 0.98 +/- 0.07; P < 0.05), heart rate (13.5 +/- 3.1 beats/min; F = 2.9; P < 0.03), and systolic blood pressure (F = 2.7; P < 0.05), whereas diastolic blood pressure did not show significant variation. Plasma leptin levels decreased by the end of the infusion (from 63 +/- 13 to 49 +/- 11 ng/mL; P < 0.05), and ob messenger ribonucleic acid levels were significantly reduced (decrease amounting to 47 +/- 5% of basal values). Our study shows that adrenergic activation contributes to regulate ob messenger ribonucleic acid levels in humans. The interaction between epinephrine and leptin may operate during metabolic and psychological stress to regulate energy expenditure and food intake.

Adipose Tissue↗
PubMed1998

Acute infusion of naloxone, an opioid receptor antagonist, does not modify serum leptin concentrations in amenorrheic and healthy women.

OBJECTIVE: To determine whether the opioidergic system is involved in the modulation of leptin secretion in healthy and amenorrheic subjects. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology, University of Modena, Modena, Italy. PATIENT(S): Healthy subjects (n = 8) and patients with hypothalamic amenorrhea (n = 17) or hyperandrogenism (n = 7) and low body mass index (BMI). INTERVENTION(S): Acute infusion of naloxone (4-mg bolus) and blood sampling 15 minutes before infusion; at time of infusion; and 15, 30, 45, 60, 75, 90, and 120 minutes after infusion. MAIN OUTCOME MEASURE(S): Plasma leptin, LH, FSH, E2, and cortisol concentrations. RESULT(S): Plasma leptin concentrations were lower (P <.01) in both hypothalamic and hyperandrogenic amenorrheic subjects than in healthy controls. In all groups of subjects, no significant changes in leptin levels were observed after infusion of naloxone. A significant correlation was found between leptin concentrations and BMI when all subjects were considered together (P <.05) but was not found in the single groups. CONCLUSION(S): The present data do not support the hypothesis that opioidergic receptors are involved acutely in the modulation of leptin release in healthy and amenorrheic women.

Amenorrhea↗
PubMed1998

Effects of galanin and the galanin receptor antagonist galantide on plasma catecholamine levels during a psychosocial stress stimulus in rats.

The aim of this study was to investigate the role played by the neuropeptide galanin (GAL) in the regulation of sympathoadrenal function. We evaluated the effects of rat GAL (rGAL) and of the putative GAL receptor antagonist galantide (GLT) on epinephrine (E) and norepinephrine (NE) plasma levels in conscious freely moving male rats, during a psychosocial stress condition. Four groups of male rats were challenged by a stress stimulus, obtained by exposing the animals to a resident conspecific fighter (intruder model), following an intravenous injection with (1) rGAL + saline (SAL), (2) GLT + SAL, (3) rGAL + GLT, or (4) SAL + SAL. Plasma levels of both E and NE were also measured in an additional group of male rats not exposed to any stressor stimulus. The results (mean+/-SEM) showed that rats exposed to the stressor stimulus (intruder rats) exhibited a significant increase above baseline in circulating levels of both E (peak values of 834.13+/-115.13 pmol/l vs. basal values of 309.31+/-32.93 pmol/l; p < 0.01) and NE (peak values of 5,299.03+/-450.62 pmol/l vs. basal values of 2,798.24+/-311.56 pmol/l; p < 0.01) in comparison to control, nonstressed rats. The comparison of the areas under the curve response (AUC) among treatments in the intruder rats revealed that rGAL + SAL injections resulted in a further increase in E levels when compared to SAL + SAL treatment (AUC values: 8.26+/-0.64 vs. 25.38+/-5.52 nmol/ 1/20 min in SAL + SAL vs. rGAL + SAL treatment, respectively; p < 0.02). No significant changes in stress-induced E plasma levels were found following GLT + SAL treatment in comparison to SAL + SAL injections. When the intruder rats were submitted to rGAL + GLT injections, the increments in E levels were found to be higher than those observed following SAL + SAL treatment (AUC values: 8.26+/-0.64 vs. 36.00+/-13.76 nmol/ 1/20 min in SAL + SAL vs. rGAL + GLT treatment, p < 0.03); however, the values were not significantly different from those observed in rGAL + SAL-injected rats. No significant changes in stress-induced NE levels were found in either treatment group when compared to SAL + SAL-injected intruder rats. The results of this study demonstrate that rGAL administration leads to an increase in the E response to the stress stimulus without any effect on NE response. Galantide does not affect either the physiological stress-induced elevation of plasma catecholamines or the effects of rGAL on E plasma levels in response to stress. Therefore, GLT does not appear to behave as a GAL receptor antagonist in the regulation of sympathoadrenal function in rats.

Adrenal Glands↗
PubMed1998

Acute estradiol and progesterone administration reduced cardiovascular and catecholamine responses to mental stress in menopausal women.

Steroid hormones are involved in the regulation of sympathoadrenal activity. Since the effect of sex steroids on the cardiovascular system and catecholamine secretion could also be exerted through an acute, nongenomic mechanism, we have studied the response to mental stress (color word test, CWT) in a group of 15 menopausal women during estrogen (100 microg of estradiol by patch), progesterone (100 mg i.m.) or placebo administration. Systolic blood pressure (SBP) increased during CWT in the three sessions (F = 11.0, p < 0.001) but the area under the curve of SBP was higher during placebo (2,855 +/- 131 mm Hg x min) than during estradiol (2,585 +/- 139 mm Hg x min) and progesterone (2,553 +/- 179 mm Hg x min, p < 0.05 for both). Plasma epinephrine increased during CWT in the three sessions (F = 31.1, p < 0.001) and the plasma epinephrine response to mental stress was higher during placebo than during estradiol administration (F = 4.3, p < 0.01). The area under the curve of epinephrine was 10,342 +/- 1,348 pmol/min x 1 during placebo and 7,280 +/- 818 pmol/min x 1 during estradiol (p < 0.03). The plasma glycerol levels at the end of CWT were higher during placebo (0.26 +/- 0.04 nmol/l) than during estradiol (0.19 +/- 0.03 mmol/l) and progesterone (0.17 +/- 0.04 mmol/l) administration (p < 0.05 for both). No significant differences were found in the responses of diastolic blood pressure, heart rate, norepinephrine and cortisol to mental stress during placebo and estradiol or progesterone administration. This study demonstrates that acute steroid administration is able to modify the cardiovascular and catecholamine response to mental stress in menopausal women.

Adrenal Glands↗
PubMed1997

Alpha-2 adrenergic activity in perimenopausal women.

Lipid alterations and increased blood pressure may occur during perimenopause. No data are available in perimenopausal women on the alpha-2 adrenergic activity which affects norepinephrine secretion. We studied cardiovascular and catecholamine responses to clonidine (300 mg per os) in a group of 15 perimenopausal women (PeriMW) and in a control group of 13 premenopausal women (PreMW). Nine of the perimenopausal women were also studied after 4-month percutaneous estrogen replacement therapy (PeriMWE). Systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), plasma norepinephrine (NE) and epinephrine (E) were evaluated before and at 120 min, 130 min, 140 min after clonidine administration. Basal values of SBP, DBP and HR were not different (F = 0.7, p = NS; F = 0.2, p = NS and F = 0.1, p = NS respectively) between PeriMW both before and after therapy and PreMW. Resting levels of E were similar in PreMW and in PeriMW before and during estrogen therapy (F = 0.8, p = NS); PeriMW showed higher basal NE levels both before and during estrogen therapy than PreMW (F = 12; p < 0.001). Clonidine administration decreased SBP, DBP and NE levels in PreMW, in PeriMW and in PeriMWE without any difference between the groups (F = 1.2, p = NS; F = 0.5, p = NS and F = 1.3, P = NS respectively). HR decreased significantly after clonidine in PreMW (F = 5.4, p < 0.03) but not in PeriMW before (F = 1.0, p = NS) and during estrogen therapy (F = 0.5, p = NS). Clonidine did not affect plasma E in the three groups studied (F = 2.8, p = NS; F = 2.2, P = NS and F = 0.1, p = NS). The present study demonstrates that increased basal plasma NE levels are present in PeriMW. The cardiovascular and catecholamine response to clonidine in PeriMW both before and during estrogen therapy are similar to those observed in PreMW, suggesting a normal inhibitory alpha-2 receptor pathway.

Adrenergic alpha-Agonists↗
PubMed1997

Cholinergic enhancement by pyridostigmine increases the insulin response to glucose load in obese patients but not in normal subjects.

OBJECTIVE: To further investigate the role, if any, of acetylcholine and the parasympathetic nervous system in modulating beta-cell secretion in man. DESIGN: Oral glucose load (OGTT, 100 g p.o. at 0 min) alone and preceded by pyridostigmine (PD, 120 mg p.o., 60 min before OGTT), a cholinesterase inhibitor, were administered on two different occasions, in random order, two or three days apart. SUBJECTS: Ten women with central obesity (OB, body mass index (BMI): 34.2 +/- 2.1 kg/m2, waist to hip ratio (WHR): 0.83 +/- 0.01, aged 39.0 +/- 5.3y) and six normal women (NS, BMI: 22.7 +/- 1.9 kg/m2, WHR: 0.74 +/- 0.01, aged 37.1 +/- 4.8y) were studied. MEASUREMENTS: Serum insulin, plasma glucose and plasma noradrenaline (NA) were measured at -60, -15 and 0 min, and then every 15 min up to +120 min. Insulin concentrations were measured in duplicate by immunoradiometric assay, glucose by glucose oxidase colorimetric method and NA was assayed after extraction with alumina using high performance liquid chromatography with electrochemical detection. Pulse rate (PR), systolic (SBP) and diastolic blood pressure (DBP) were also measured every 15 min during the tests by an automated cuff device. RESULTS: OGTT raised glucose concentrations in OB and NS (incremental area: 420 +/- 44 vs 288 +/- 70 mmol/l. 2 h, respectively) without significant differences between groups (F = 0.6, P = ns). On the other hand, OB showed an insulin response to OGTT higher than NS (10,120 +/- 1074 vs 6692 +/- 1962 microU ml-1 2 h, respectively P < 0.01). After OGTT alone NA concentrations increased to the same extent in NS (peak vs basal: 1.40 +/- 0.16 vs 1.07 +/- 0.10 nmol/l, P < 0.05) and in OB (peak vs basal: 1.50 +/- 0.14 vs 1.04 +/- 0.18 nmol/l P < 0.05). Both in NS and in OB, PD administration failed to modify basal glucose and insulin (P = ns for both) as well as basal NA concentrations. In NS, the combined administration of PD and OGTT did not modify glucose and insulin responses compared to OGTT alone 335 +/- 65.4 mmol/l. 2h and 6348 +/- 1348 microU ml-1 2h, respectively) while in OB, PD significantly increased the insulin response to OGTT (14640 +/- 3030 microU ml-1 2h, P < 0.03), while the glucose response was not significantly different from OGTT alone (478 +/- 45 mmol/l. 2h). PD administration did not modify the NA response to OGTT, in NS or OB (P = ns). In both groups, pyridostigmine administration did not affect systolic or diastolic blood pressures, but decreased pulse rate to the same extent in NS (74 +/- 2 vs 66 +/- 2 beats/min, P < 0.05) and in OB (72 +/- 1 vs 67 +/- 2 beats/min, P < 0.05). CONCLUSIONS: Our present data indicate that in man, as in animals, acetylcholine has a stimulatory influence on insulin secretion.

Abdomen↗
PubMed1996

The effects of clonidine on blood pressure, catecholamine and growth hormone release in hypogonadal men is preserved and not influenced by testosterone replacement therapy.

It has been demonstrated that castration impairs the hypotensive effect of clonidine in rat as well as its GH-releasing activity while testosterone replacement restores to normal the effects of alpha-2 adrenoceptor activation. Thus, these data point to main role of the gonadal steroid testosterone in modulating the effects of alpha-2 adrenergic activation on blood pressure, catecholamine and GH release in animal. Aim of the present study was to verify the activity of clonidine on blood pressure, catecholamine and GH release in human male hypogonadism before and after testosterone replacement. To this goal, 14 hypogonadal men (HP, age 33.8 +/- 2.9 yr; BMI < 25 kg/m2; 8 with hypergonadotropic and 6 with hypogonadotropic hypogonadism) received clonidine administration (CLON, 300 micrograms po at 0 min) before and after 3 months of testosterone replacement (testosterone propionate depot, 250 mg i.m. every 21 days). Ten normal adult volunteers (NS, age 31.5 +/- 1.9 yr; BMI < 25 kg/m2) were studied as control group. In all subjects, before and after clonidine administration, systolic and diastolic blood pressure (SBP and DBP), pulse rate (PR), norepinephrine (NE), epinephrine (E) and GH levels were recorded. In HP basal testosterone levels were lower than those in NS (1.25 +/- 0.3 vs 7.34 +/- 1.5 ng/ml, p < 0.05) and were restored to normal by hormonal replacement (6.91 +/- 1.3 ng/mL) in HP, both SBP and DBP as well as PR were normal in basal conditions and were not modified by testosterone replacement. Both before and during testosterone CLON lowered SBP, DBP and PR in HP to the same extent observed in NS. In HP, basal NE levels were lower than those in NS (0.85 +/- 0.15 vs 1.28 +/- 0.19 nmol/l, p < 0.05) and were restored to normal during testosterone replacement (1.25 +/- 0.13 nmol/l). On the other hand, basal E levels in HP were similar to those in NS (179 +/- 42 vs 197 +/- 38 pmol/l) and were not modified by testosterone therapy (167 +/- 28 pmol/l). In HP, both before and during testosterone replacement, CLON reduced NE (0.44 +/- 0.10 and 0.58 +/- 0.07 nmol/l) levels to the same levels recorded in NS (0.68 +/- 0.08 nmol/l). Basal GH and IGF-I levels in HP (1.15 +/- 0.5 and 234 +/- 42 micrograms/l, respectively) were similar to those in NS (1.18 +/- 0.4 and 221 +/- 38 micrograms/l, respectively) and were not modified by testosterone (1.35 +/- 0.6 and 256 +/- 32 micrograms/l, respectively). CLON administration induced a clear GH response in HP (F = 37; p < 0.001) which overlapped with that recorded in NS and was not modified by testosterone (F = 1.7; P = NS). Our present findings demonstrate that, differently from in animal, in man testosterone has no role in modulating the effects of alpha-2 adrenergic activation by clonidine on blood pressure, catecholamine and GH release. On the other hand, our data suggest the existence in male hypogonadism of a reduced basal noradrenergic activity which is restored by testosterone replacement.

Adult↗