Objectif L’apeline est une adipocytokine hyperexprimée en conditions d’obésité, impliquée dans l’équilibre hydrique et la fonction cardiovasculaire. Étant colocalisée dans les neurones magnocellulaires hypothalamiques avec l’arginine-vasopressine (AVP) et ayant des effets diurétiques [1], nous avons étudié les taux sériques d’apeline et copeptine chez des hommes hypertendus (HT) et normotendus avec (NT+) et sans (NT-) histoire familiale d’HTA, soumis à un test de charge hydrique. Méthodes Quatre-vingt-six hommes caucasiens non-obèses ont été invités à boire 15–20mL/kg d’eau durant 40–45minutes, suivi d’une surveillance clinique et biologique pendant 4h. Les concentrations sériques de copeptine et apeline ont été mesurées par ELISA au début du test, 120 et 240minutes après. Résultats En réponse à la charge hydrique, la TA augmentait avec un pic à 20–40minutes dans tous les groups. Inversement, les taux sériques de copeptine, effondrés à 120minutes, revenaient progressivement aux niveaux basaux à 240minutes. Une tendance opposée était observée pour les taux d’apeline et le rapport apeline/copeptine. Significativement, les hommes HT et NT+ présentaient des taux plus faibles d’apeline et plus élevés de copeptine que les sujets NT-. Discussion Nos résultats suggère l’existence chez les hommes HT et NT+ d’une dysrégulation de la balance AVP/apeline qui pourrait contribuer à la susceptibilité et/ou aux stades précoces du développement de l’HTA, ouvrant la voie à des nouvelles stratégies thérapeutiques et/ou préventives dans la régulation de la TA et le risque cardiovasculaire corrélé [1], [2].

Abstract Background/Introduction Hypertension (HTN) and metabolic syndrome (MetS) are both leading risk factors for major cardiovascular diseases, which frequently coexist as a complicated cardiometabolic disorder. The cardiac hormone atrial natriuretic peptide (ANP) plays a key role in both blood pressure and metabolic regulation through activation of the guanylyl cyclase-A receptor (GC-A) and the second messenger 3’,5’ cyclic guanosine monophosphate (cGMP). Indeed, ANP decreases blood pressure, induces lipolysis by increasing plasma levels of non-esterified fatty acids (NEFA) and improves insulin-sensitivity. MANP is a new Mayo Clinic designed natriuretic peptide consisting of the native ANP with a 12-amino-acid C-terminus extension and its biological actions are mediated by the GC-A/cGMP pathway. MANP is less susceptible to neprilysin degradation and exert more sustained cGMP dependent biological actions than ANP. Purpose In a proof-of-principle human study, for the first time we aimed to determine the cardiovascular and metabolic properties of MANP, a novel ANP analog, in the clinical setting of HTN with MetS. Methods We conducted a double-blind, placebo-controlled trial in 22 patients (17 receiving MANP) with HTN and MetS involving single subcutaneous injection of MANP (2.5 µg/kg) or placebo (NCT03781739). Blood pressure (BP) and circulating cGMP were monitored for 24 hours post treatment. Circulating metabolic parameters including insulin, glucose, non-esterified fatty acids (NEFA) and insulin resistance (HOMA-IR) and insulin sensitivity (HOMA-IS) indexes were assessed for the first 4 hours post treatment. Results Compared to baseline, MANP increased plasma cGMP at 30 minutes (delta: 4.8 ± 2.0 pmol/mL, P = 0.02) and 1 hour (delta: 2.9 ± 1.3 pmol/mL, P = 0.03) post injection. At 6 hours, systolic BP decreased by 5.7 ± 2.9 mmHg (P = 0.06) in the MANP group, whereas no reduction in BP was observed in placebo group. Among the 17 subjects receiving MANP, lower baseline cGMP levels were associated with greater mean reductions in systolic BP (ρ = 0.66, P = 0.005). After MANP injection, glucose levels decreased at 2 (delta: -4.7 ± 2.1 mg/mL, P = 0.04) and 4 hours (delta: -13.1 ± 3.9 mg/mL, P = 0.003) compared to baseline while insulin levels remained stable. During the first 4 hours post injection, we also observed a trend of increase in insulin sensitivity index (HOMA2-IS) and decrease in insulin resistance index (HOMA2-IR) with MANP, both were opposite to the trends in placebo. At 1 hour post MANP administration, NEFA increased by 108.2 ± 37.4 µM compared to baseline (P = 0.01). Conclusion(s) Our findings support the favorable cardiovascular and metabolic actions of MANP as a potential therapeutic strategy for HTN with MetS.

Objective: Cachexia is a severe complication of advanced heart failure and chronic kidney disease. We previously reported that high dose Angiotensin II infusion in rats determined body weight reduction, prevented by an AT-1 receptor blocker treatment and beta-adrenergic non selective antagonism. The possible role of Ang II on UCP1 in white and brown adipose tissue, as a possible mechanism, was investigated in this study. Design and method: Male Sprague-Dawley rats, were implanted subcutaneously in the dorsal region with osmotic minipumps delivering Ang-II at high doses (525 ng/Kg/min) for 12 days to mimic heart failure and the development of cachexia. Five concurrent groups of rats were evaluated: 1) vehicle–infused rats (CTR-rat, n = 9); 2) Ang-II infused rats (n = 7); Ang- II rats receiving by oral gavage 2 days before minipump implantation until the 12th day of Ang-II infusion, either 3) bisoprolol (BIS,β1-adrenergic antagonist, 35 mg/Kg/day, n = 5), or 4) carvedilol (CVD,α1-non-selective-β1,2,3-adrenergic blocker, 90 mg/kg/day, n = 5) or 5) bupranolol (BPR,β3-antagonist, 200 mg/day/kg, n = 4). White adipose tissue (WATs) from retroperitoneal (RWAT), epidydimal (EWAT), dorsal (DWAT) and brown interscapular (IBAT) depot were withdrawn in order to determine UCP1 mRNA expression, norepinephrine tissue level (TNE) and tyrosine hydroxylase activity (THA) Results: THA and TNE were higher in Ang-II infused rats in all the white adipose tissue depots analyzed. CVD prevented TNE increase in all WATs, while BPR and BIS were effective in RWAT and EWAT but not DWAT. All the three beta adrenergic blocker treatments significantly reduced THA increased activity related to Ang-II infusion in all the WATs. UCP1 mRNA was increased in IBAT (+39%, p < 0.05) of Ang II-infused rat, significantly prevented by CVD and BPR but not by BIS. UCP1 was also increased in all the three WATs of Ang-II infused rats, with all the three beta blockers able to reduce the effect in RWAT and DWAT. No effect of beta-blockers treatment was observed in EWAT. Conclusions: High dose angiotensin II infusion determined an increase in UCP1 trascription in brown and white adipose tissue in rats. CVD and BPR were able to prevent UCP1 increase in brown and white adipose tissue more than beta-1 selective antagonist BIS.

Objective: Nitric oxide is an important modulator of vascular tone but also of the sodium and water balance. These phenomena appear to be of particular relevance in the control of blood pressure and the development of arterial hypertension. Design and method: We evaluated in 4 week-old Wistar Kyoto normotensive rats the effects of chronic inhibition of nitric oxide synthase through NG-nitro-L-arginine methyl ester (L-NAME, 7.5 mg / kg / day per 4 weeks) on water and sodium balance. Results: The dose of L-NAME administered orally for 4 weeks did not generate a significant increase in blood pressure (116 ± 10 vs 112 ± 8). The volume of diuresis was reduced, associated with an increase in urine osmolarity in the group treated with L-NAME. Natriuresis levels were not significantly different between L-NAME treated and untreated rats. Urinary aquaporin2/creatinine ratio was significantly elevated in L-NAME group of rat (p < 0.05). Plasma and urinary metabolites of nitric oxide (NOx) were reduced in L-NAME treated rats as compared to untreated. Conclusions: These results support that nitric oxide synthase inhibition, at subpressor doses, determine a positive water balance by increasing tubular effect of vasopressin that lead to higher tubular water channel (aquaporin2) expression, and subsequently to the shedding in the urine.

Objective: Cardiac cachexia development in heart failure is characterized by fat mass loss and elevated levels of circulating fatty acid (FA). Zinc alpha 2 glycoprotein (ZAG) has been demonstrated to induce lipolysis in vivo in rodents and in cardiac cachexia. We investigate ZAG mechanisms of action in human adipocytes obtained from healthy subjects (CTR), heart failure non cachectic patients (HFnCX) and cardiac cachectic patients (HFCX). Design and method: Two sets of experiments have been performed: in the first pilot study 6 CTR, 4 HFnCX and 3 HFCX subjects have been enrolled. Subcutaneous adipose tissue sample has been obtained during dermatological surgical procedure or at the moment of ICD or PM generator change. Isolate mature adipocytes were incubated with ZAG 25 ug/mL. H2O2 release in culture medium was evaluate before and after 1 and 2 hours of ZAG-incubation. Adipocytes have been also incubated with Norepinephrine (NE) 10-5 M, H2O2 10-4 M and 10-5 M and BRL44408 10-5 M (Selective alpha2A-adrenoceptor antagonist). Infranatant glycerol was measured as an index of lipolysis. In the second set of experiments 16 CTR, 19 HFnCX and 12 HFCX patients have been enrolled. Adipocytes were incubated with ZAG 25 ug/mL, Benzylamine (BZ) 1 mM and Tyramine (TY) 1 mM in different combination and H2O2 production was measured. Results: ZAG did not increased lipolysis but co-incubation with noradrenaline resulted in higher glycerol release in HFCX vs noradrenaline alone (+60%,p < 0.05). ZAG reduced H2O2 release from adipocytes to a greater extent in HFCX (+65%,p < 0.05) whitin the first hour of incubation. H2O2 incubation with adipocytes did not reduce glycerol release in the three group, nor reduced the NE-mediated lipolysis. H2O2 blunted the BRL44408-induced lipolysis when co-incubated with NE. A greater release of H2O2 from HFCX in basal condition and after incubation with BZ and TY was observed.ZAG reduced BZ-related H2O2 production in all the three groups, whereas TY did not. Conclusions: ZAG has a facilitating role in NE-induced lipolysis that could be linked to an antioxidant, reducing H2O2 levels especially in HFCX patients. ZAG reduced BZ-related semi-carbazide sensitive-oxidase H2O2 generation suggesting an involvment of this enzyme in its action.

Objective: Salt retention is a condition associated with a mild inflammatory state. Recent researches pointed out the skin as central regulator of sodium balance besides the traditional “nephrocentric view”. Hypertonic skin sodium storage is associated with osmotical and immunological disregulation expressed by activation of tonicity-sensing pathways in macrophages, stimulation of lymphangiogenesis facilitating skin sodium clearance. The aim of this study is to evaluate in a model of normotensive rat the effect of two different dietary sodium regimens on the interstitial sodium levels, lymphangiogenesis and tissue macrophages expression. Design and method: Two groups of normotensive rats (Wistar Kyoto) were fed for three weeks with two different dietary regimens, respectively, High Salt Diet (HSD, NaCl 8%) and Low Salt Diet (LSD, NaCl 0,08%). Interstitial subcutaneous sodium concentration was measured by microdialysis procedure. Tissue evaluation of Macrophage component, endothelial and lymphatic capillary density was evaluated by Immunohystochemistry analysis. Macrophage was detected by anti CD-68 antibodies, vascular endothelial structures revealed by von Willebrand Factor antibodies and the lymphatic elements by Podoplanin (D2-40) antibodies. Results: There was no significant difference between interstitial sodium concentration and sodium plasma levels (144mmol/L vs 146 mmol/L). Hystological differences were found in the two groups (HSD and LSD): measurements of lymphatic podoplanin (D2-40) component and endothelial structures were different (average of vessels number per mm2 (D2-40: HSD 3,90 vs LSD 2,08; von-Willebrand: HSD 6,04 vs LSD 4,62). Similarly, macrophage population average of number of cells per mm2 area was higher in HSD (CD 68+: 6,90) vs LSD (CD68+:5,65). Conclusions: The effect of an high salt dietary intake bursts an inflammatory response supporting the idea that interstitial tonicity variations may be related to macrophage activation and, consequently, lympho-endothelial expression. HSD did not lead to any difference in interstitial sodium concentration assuming an adeguate ability in drainage of skin sodium excess in a model of normotensive rat.

Objective: Salt retention is a condition associated with a mild inflammatory state. Recent researches pointed out the skin as central regulator of sodium balance besides the traditional “nephrocentric view”. Hypertonic skin sodium storage is associated with osmotical and immunological disregulation expressed by activation of tonicity-sensing pathways in macrophages, stimulation of lymphangiogenesis facilitating skin sodium clearance. The aim of this study is to evaluate in a model of normotensive rat the effect of two different dietary sodium regimens on the interstitial sodium levels, lymphangiogenesis and tissue macrophages expression. Design and method: Two groups of normotensive rats (Wistar Kyoto) were fed for three weeks with two different dietary regimens, respectively, High Salt Diet (HSD, NaCl 8%) and Low Salt Diet (LSD, NaCl 0,08%). Interstitial subcutaneous sodium concentration was measured by microdialysis procedure. Tissue evaluation of Macrophage component, endothelial and lymphatic capillary density was evaluated by Immunohystochemistry analysis. Macrophage was detected by anti CD-68 antibodies, vascular endothelial structures revealed by von Willebrand Factor antibodies and the lymphatic elements by Podoplanin (D2-40) antibodies. Results: There was no significant difference between interstitial sodium concentration and sodium plasma levels (144mmol/L vs 146 mmol/L). Hystological differences were found in the two groups (HSD and LSD): measurements of lymphatic podoplanin (D2-40) component and endothelial structures were different (average of vessels number per mm2 (D2-40: HSD 3,90 vs LSD 2,08; von-Willebrand: HSD 6,04 vs LSD 4,62). Similarly, macrophage population average of number of cells per mm2 area was higher in HSD (CD 68+: 6,90) vs LSD (CD68+:5,65). Conclusions: The effect of an high salt dietary intake bursts an inflammatory response supporting the idea that interstitial tonicity variations may be related to macrophage activation and, consequently, lympho-endothelial expression. HSD did not lead to any difference in interstitial sodium concentration assuming an adeguate ability in drainage of skin sodium excess in a model of normotensive rat.

Objective: Evidences indicate that in addition to long term regulation of blood pressure, in the kidney resides the initial trigger for the development of hypertension. Altered capacity of the kidney to excrete sodium and water in relation to intake has been proposed as a basic mechanism of initiating hypertension. Betaine is one of the major organic osmolytes and the upregulation of its betaine/gamma-aminobutyric acid transporter (BGT1) in the renal medulla is related to high extracellular tonicity and urinary osmolality. Design and method: The present study investigated the abnormalities in water and sodium balance and osmoregulation in a model of polygenic multifactorial arterial hypertension, the spontaneously hypertensive rats (SHR, n = 58) and compared with their normotensive controls Wistar Kyoto (WKY, n = 46 from their prehypertensive phase (4 weeks of age) until the development hypertension and of organ damage (28–30 weeks of age). Rats were housed in metabolic cages to monitor water and salt balance parameters at the age of 4–5, 14–16 and 28–30 weeks of age. Results: No difference of blood pressure (both indirectly tail cuff method and invasively, as well heart rate, body weight, serum sodium, potassium and creatinine levels) was measured at the age of 5 weeks of age between SHR and WKY. Daily urinary volume was reduced in prehypertensive SHR as compared to WKY (-36 %, p < 0.01) with an increased urinary osmolality (p < 0.01); a trend toward reduced urinary sodium excretion (p = 0.079) in prehypertensive SHR was observed as compared with WKY. A marked accumulation of BGT1 is observed in outer medulla of SHR (mTHAL) as compared to WKY and its expression is directly correlated with urinary osmolarity. Arginin vasopressin circulating levels were not different between prehypertensive SHR and WKY whereas urinary aquaporin 2/creatinine ratio excretion was higher in prehypertensive SHR vs WKY. At the age of 28–30 weeks, hypertensive SHR with moderate renal failure did not show any difference in urinary osmolarity, renal expression of BGT1 as compared with WKY. Conclusions: All these results suggest in prehypertensive SHR an early positive balance of water before sodium balance alteration.

Objective: Evidences indicate that in addition to long term regulation of blood pressure, in the kidney resides the initial trigger for the development of hypertension. Altered capacity of the kidney to excrete sodium and water in relation to intake has been proposed as a basic mechanism of initiating hypertension. Betaine is one of the major organic osmolytes and the upregulation of its betaine/gamma-aminobutyric acid transporter (BGT1) in the renal medulla is related to high extracellular tonicity and urinary osmolality. Design and method: The present study investigated the abnormalities in water and sodium balance and osmoregulation in a model of polygenic multifactorial arterial hypertension, the spontaneously hypertensive rats (SHR, n = 58) and compared with their normotensive controls Wistar Kyoto (WKY, n = 46 from their prehypertensive phase (4 weeks of age) until the development hypertension and of organ damage (28–30 weeks of age). Rats were housed in metabolic cages to monitor water and salt balance parameters at the age of 4–5, 14–16 and 28–30 weeks of age. Results: No difference of blood pressure (both indirectly tail cuff method and invasively, as well heart rate, body weight, serum sodium, potassium and creatinine levels) was measured at the age of 5 weeks of age between SHR and WKY. Daily urinary volume was reduced in prehypertensive SHR as compared to WKY (-36 %, p  Conclusions: All these results suggest in prehypertensive SHR an early positive balance of water before sodium balance alteration.

Objective: Renal vasodilatation during L-arginine (ARG) infusion is impaired in essential hypertensive (HTN) vs. healthy (C) humans. Whether or not different ARG effects on the oxidative stress (OS) do participate in such abnormal responses is not known. Design and method: Mean arterial pressure (MAP), glomerular filtration rate (GFR, inulin), renal blood flow (RBF, p-aminohippurate), and urinary excretion of sodium (UNaV), NO2+NO3 (UNOxV), and 8-isoprostane (U8-iso-PGF2alfaV) were measured in 16 salt-repleted C and 19 HTN undergoing 3-hours infusion of 0.012 mmol.kg.min-1 ARG.HCl. Results: In contrast to the markedly decreased U8-iso-PGF2alfaV with ARG.HCl in C, in HTN a slightly increased U8-iso-PGF2alfaV is associated with impaired renal vasodilatation. Therefore, a net reduction in the baseline OS related to the augmented NO bioavailability likely participates physiologically in renal responses to ARG.HCl. In HTN, a limited or abolished capacity of ARG.HCl to affect baseline OS, consistent with impaired scavenging of Reactive Oxygen Species by NO and/or increased formation of peroxynitrite from NO, could contribute to the reduced renal hemodynamic response. Conclusions: In contrast to the markedly decreased U8-iso-PGF2alfaV with ARG.HCl in C, in HTN a slightly increased U8-iso-PGF2alfaV is associated with impaired renal vasodilatation. Therefore, a net reduction in the baseline OS related to the augmented NO bioavailability likely participates physiologically in renal responses to ARG.HCl. In HTN, a limited or abolished capacity of ARG.HCl to affect baseline OS, consistent with impaired scavenging of Reactive Oxygen Species by NO and/or increased formation of peroxynitrite from NO, could contribute to the reduced renal hemodynamic response.

Objective: Evidences indicate that in addition to long term regulation of blood pressure, in the kidney resides the initial trigger for the development of hypertension. Altered capacity of the kidney to excrete sodium and water in relation to intake has been proposed as a basic mechanism of initiating hypertension. Betaine is one of the major organic osmolytes and the upregulation of its betaine/gamma-aminobutyric acid transporter (BGT1) in the renal medulla is related to high extracellular tonicity and urinary osmolality. Design and method: The present study investigated the abnormalities in water and sodium balance and osmoregulation in a model of polygenic multifactorial arterial hypertension, the spontaneously hypertensive rats (SHR, n = 58) and compared with their normotensive controls Wistar Kyoto (WKY, n = 46 from their prehypertensive phase (4 weeks of age) until the development hypertension and of organ damage (28–30 weeks of age). Rats were housed in metabolic cages to monitor water and salt balance parameters at the age of 4–5, 14–16 and 28–30 weeks of age. Results: No difference of blood pressure (both indirectly tail cuff method and invasively, as well heart rate, body weight, serum sodium, potassium and creatinine levels) was measured at the age of 5 weeks of age between SHR and WKY. Daily urinary volume was reduced in prehypertensive SHR as compared to WKY (-36 %, p < 0.01) with an increased urinary osmolality (p < 0.01); a trend toward reduced urinary sodium excretion (p = 0.079) in prehypertensive SHR was observed as compared with WKY. A marked accumulation of BGT1 is observed in outer medulla of SHR (mTHAL) as compared to WKY and its expression is directly correlated with urinary osmolarity. Arginin vasopressin circulating levels were not different between prehypertensive SHR and WKY whereas urinary aquaporin 2/creatinine ratio excretion was higher in prehypertensive SHR vs WKY. At the age of 28–30 weeks, hypertensive SHR with moderate renal failure did not show any difference in urinary osmolarity, renal expression of BGT1 as compared with WKY. Conclusions: All these results suggest in prehypertensive SHR an early positive balance of water before sodium balance alteration.

Optimal nutritional requirements and nutrient intake composition for patients with acute kidney injury is still a partially unresolved issue. Targeting nutritional support to the actual protein and energy needs improves the clinical outcome of critically ill patients. So far, very few data are currently available on this topic in acute kidney injury. In this specific clinical condition, the risk for under- and overfeeding may be increased by factors interfering on nutrient need estimation, such as rapidly changing body weight due to fluid balance variations, nutrient losses and hidden calorie sources from renal replacement therapy. Moreover, since acute kidney injury is now considered a kidney-centered inflammatory syndrome, the renoprotective role of specific pharmaconutrients with anti-inflammatory properties remains to be fully defined. This review is aimed at discussing recently published results concerning quantitative and qualitative aspects of the nutritional approach to acute kidney injury in critically ill patients.

Cabassi, A.; Halpert, S.; Theullet, M.; Vinci, S.; Moschini, L.; Govoni, P.; Borghetti, A.; Tedeschi, S.; Binno, S.; Coghi, P.; Montanari, A.; Parenti, E.; Cremaschi, E.; Regolisti, G.; Fiaccadori, E. Author Information

Cardiac cachexia including fat loss is detrimental for advanced aged heart failure patients. Advanced heart failure is characterized by neurohormonal and oxidative stress imbalance. This study evaluated in old male spontaneously hypertensive rats (SHR), developing heart failure, the effects of long-term inhibition of NAD(P)H oxidase with Apocynin on subcutaneous white adipose tissue lipid metabolism and sympathetic turnover, expressed by interstitial norepinephrine release (NE) and presynaptic NE reuptake evaluation (through desipramine microdialysis probe perfusion). Blood pressure, heart rate and body weight were measured on 51 SHR from 72 weeks old until the development of overt heart failure. Thirteen age-matched Wistar-Kyoto rats (WKY) were normotensive controls. At 72 weeks, SHR underwent a basal microdialysis procedure which showed a higher interstitial subcutaneous glycerol level, expressing an increased local triglyceride breakdown and lipolysis, and higher NE level associated with a reduced presynaptic reuptake as compared to WKY. SHRs were then separated: 1) untreated SHR (n = 27) and 2) SHR (n = 24) treated with Apocynin (2.5 mg/kg/d in drinking water) until death or 88 weeks of age, when the rats repeated the microdialysis procedure.Thirty-three % of untreated SHR showed a body weight reduction of more than 15% (at 88 weeks of age) whereas in Apocynin-treated SHR only 4 (16%) developed cachexia. Glycerol interstitial levels were higher in cachectic than non-cachectic untreated SHR. Cachectic SHR showed higher NE level and a blunted response to desipramine, indicating a marked reduction of presynaptic reuptake. Non-cachectic apocynin-treated SHR showed a reduced interstitial level of glycerol and NE and improved presynaptic NE reuptake. These results suggest that chronic Apocynin treatment could improve subcutaneous NE reuptake and reduce interstitial NE concentrations and NE-induced lipolysis, as expressed by lower interstitial glycerol level. This drug seems to be able to attenuate cachexia development in this animal model of heart failure.

IntroductionIn order to find out the frequency rates of domestic and wild animal bites as well as the evaluation of the prevalence rates of rabies disease in the human population in the Province of Kerman, a retrospective study was designed to analyze statistically the collected recorded data related to this project.Methods This study was conducted within the framework of MPVM student research projects by means of collaboration between

Introduction.Body weight reduction represents the main step in the management of overweightobese hypertensive patients.Plasma RBP-4 levels are elevated in several experimental models of insulin resistance even if their relationship is less clear.Aim.Our study evaluated the effect of an intensive dietetic treatment on blood pressure levels, on homeostasis model assessment of insulin resistance index (HOMA-IR), on body weight change in a group of patients affected by high blood pressure (stage 1), overweight or obese (n=31, age 19-66 years, BMI 28,3-34,4 Kg/m2).Methods.Plasma RBP-4 and catecholamine levels were determined before and after the dietetic treatment period.Diet was administered for 24 weeks (caloric intake 1700 Kcal/die, Na <130 mEq/die, K 4 g/die, Ca 1100 mg/die and Mg 430 mg/die) and checked by periodic urine sampling and analysis of electrolyte secretion (every 6 weeks).Results.After 24 weeks, 25 patients completed the study (drop out of 6 patients) body weight was reduced (range 1,1-9,7 Kg) and blood pressure levels were normalized (28%, <140/90 mm Hg) in 7 out of 25 patients.HOMA-IR was reduced (-13%, p<0.05) as well as plasma RBP-4 (34,4 + 7,3 umol/l before and 26,4 + 5,9 umol/l after diet period, -16 % (p<0.05); a trend of reduction was observed in plasma norepinephrine levels (from 191 + 54 to 173 + 42 pg/ml, -13 %, p=0.067).No significant correlation was found between RBP-4 and norepinephrine plasma levels.Conclusions.An intensive low-caloric dietetic treatment including a reduced sodium intake, an increased potassium, calcium and magnesium intake improved insulin sensitivity and reduced plasma RBP-4 levels; Sympathetic activity was also partially lowered after the diet period without a relationship with RBP-4 reduction.