Overactivity of the sympathetic nervous system plays an important role in the development and pro... more Overactivity of the sympathetic nervous system plays an important role in the development and progression of hypertension. Catheter-based renal nerve ablation for treatment of drug-resistant hypertension has been recently developed. An alternative strategy for modulation of sympathetic nerve function is to reduce the biosynthesis of norepinephrine (NE) via inhibition of dopamine β-hydroxylase (DβH), the enzyme that catalysis the conversion of dopamine to NE in sympathetic nerves. Renal denervation (RDN) was performed in spontaneously hypertensive rats (SHR) to evaluate the effect of RDN on NE levels and blood pressure throughout a 28-day period. Chronic oral treatment with the peripheral selective DβH inhibitor etamicastat (30 mg/kg/day) was performed in another cohort of SHR. RDN and chronic oral treatment with etamicastat did not affect renal function, as assessed by urinary protein, creatinine and urea levels. RDN significantly decreased mean arterial blood pressure (MAP, in mm H...
ABSTRACT Introduction Eating disorders (ED) like anorexia nervosa (AN), bulimia nervosa (BN) and ... more ABSTRACT Introduction Eating disorders (ED) like anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED) have complex psychopathological manifestation most presumably with a multifactor etiology. Abnormal feeding had long been linked to disruptions in brain dopaminergic activity. In humans, dopamine (DA) release in the dorsal striatum regulates feeding behavior and correlates with the degree of pleasure experienced while eating. Lower availability of DA could contribute to appetite dysregulation, binge eating behavior and lack of pleasure connected with meals. DA is metabolized, amongst others, by catechol-O-methyltransferase (COMT). Previous studies found an association between eating disorders and functional polymorphisms of COMT gene. Objectives To evaluate soluble COMT activity in erythrocytes from patients with anorexia, bulimia and binge eating disorders. Diagnostic was made by a senior psychiatry using the Structured Clinical Interview for DSM-IV Axis I disorders and Eating Disorder Examination Questionnaire. Results Erythrocyte COMT activity (in pmol/mg prot/h) is significantly increased in AN and BN patients (35.9±6.8 and 39.8±8.2, respectively) compared to the control group (21.2±3.6). In BED patients, COMT activity was also found higher, but due to a high variation between individual results are not significant (35.2±15.4). An interest result was also found in a group of patients with AN and BN that were being treated with a selective serotonin reuptake inhibitor (SSRI). Unexpectedly these patients presented a COMT activity level similar to the control levels. Conclusions Patients with AN and BN present higher soluble COMT activity in erythrocytes. This increase is reversed by treatment and SSRI.
Loss of salt-inducible kinase 1 (SIK1) triggers an increase in blood pressure (BP) upon a chronic... more Loss of salt-inducible kinase 1 (SIK1) triggers an increase in blood pressure (BP) upon a chronic high-salt intake in mice (Circ Res 2015;116:642-52). Here, we address possible acute mechanisms that may relate to the observed high BP in mice lacking SIK1. SIK1 knockout ( sik1 -/- ) and wild-type ( sik1 +/+ ) littermate mice were challenged for seven days with a normal- (0.3% NaCl) or high-salt (8% NaCl) diet. Systolic BP (SBP) was significantly increased in sik1 -/- mice (137.0±17.2 mmHg) after seven days of high-salt intake, as compared to sik1 +/+ mice counterparts (120.6±4.5 mmHg). The renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) were assayed in order to investigate the possible causes for the increase in SBP in sik1 -/- mice fed a high-salt diet. No differences in renin (normal-salt: 463.4±17.9, high-salt: 462.9±28.9 pg/ml) and angiotensin II (normal-salt: 45.8±10.0, high-salt: 39.0±8.5 pg/ml) serum levels were observed. The activity of dopamine β-hydr...
As the human ovarian follicle enlarges in the course of a regular cycle or following controlled o... more As the human ovarian follicle enlarges in the course of a regular cycle or following controlled ovarian stimulation, the changes in its structure reveal the oocyte environment composed of cumulus oophorus cells and the follicular fluid (FF).In contrast to the dynamic nature of cells, the fluid compartment appears as a reservoir rich in biomolecules. In some aspects, it is similar to the plasma, but it also exhibits differences that likely relate to its specific localization around the oocyte. The chemical composition indicates that the follicular fluid is able to detect and buffer excessive amounts of reactive oxygen species, employing a variety of antioxidants, some of them components of the intracellular milieu.An important part is played by albumin through specific cysteine residues. But the fluid contains other molecules whose cysteine residues may be involved in sensing and buffering the local oxidative conditions. How these molecules are recruited and regulated to intervene su...
Mice with targeted deletions of the α 2 -adrenoceptor genes were the first animal models lacking ... more Mice with targeted deletions of the α 2 -adrenoceptor genes were the first animal models lacking functional adrenoceptors. Deletion of the α 2C -receptor gene in mice has been reported in 1995 (Link et al., 1995), which was followed by α 2B - and α 2A -deficient mouse models in ...
This study investigates α2-adrenergic receptor (α2AR) mediated feedback inhibition of catecholami... more This study investigates α2-adrenergic receptor (α2AR) mediated feedback inhibition of catecholamine release from the adrenal medulla of adult (52 weeks) and old (98 weeks) spontaneously hypertensive rats (SHR) and normotensive controls Wistar Kyoto (WKY) rats. Adrenal epinephrine content as well as the spontaneous and the nicotinic-evoked release of epinephrine were similar between adult SHR and WKY rats. Aging produced a significant reduction in epinephrine synthesis in WKY rats. In contrast, in SHR aging produced a significant increase in epinephrine release without significant changes in epinephrine synthesis. The α2AR agonist medetomidine abolished (80–90% inhibition) the nicotinic-evoked release of epinephrine in adult SHR and WKY rats. With aging, this effect was unaltered in WKY rats but was significantly decreased in SHR (30% inhibition). Adrenal α2AAR mRNA levels were significantly reduced in old SHR compared with age matched WKY rats. In conclusion, in aging the α2AR mediated feedback inhibition of epinephrine release from the adrenal medulla is preserved in WKY rats but compromised in SHR, resulting in increased epinephrine release.
Aim: Statins, the mainstay in the treatment of hypercholesterolemia, are generally believed to ex... more Aim: Statins, the mainstay in the treatment of hypercholesterolemia, are generally believed to exert positive effects on CVD beyond their lipid lowering properties. Many studies have indicated that the anti-inflamma-tory effects of statins are in part responsible for this favorable influence. There are however no studies investigating how statins interact with the production of eicosanoids or other arachidonic acid (AA)-derived metab-olites in human vascular endothelial cells. Methods: Human umbilical endothelial cells were exposed to fluvasta-tin and analysed for expression of enzymes involved in the production of AA-derived metabolites using real time PCR and western blotting. The cellular formation of eicasanoids and NO were analysed by enzyme immunoassay. Moreover, the influence on the tone of resistance human arteries was assessed ex vivo. Results: A significant reduction of the expression of COX-1 mRNA after fluvastatin exposure was observed whereas mRNA expression specific fo...
Overactivity of the sympathetic nervous system plays an important role in the development and pro... more Overactivity of the sympathetic nervous system plays an important role in the development and progression of hypertension. Catheter-based renal nerve ablation for treatment of drug-resistant hypertension has been recently developed. An alternative strategy for modulation of sympathetic nerve function is to reduce the biosynthesis of norepinephrine (NE) via inhibition of dopamine β-hydroxylase (DβH), the enzyme that catalysis the conversion of dopamine to NE in sympathetic nerves. Renal denervation (RDN) was performed in spontaneously hypertensive rats (SHR) to evaluate the effect of RDN on NE levels and blood pressure throughout a 28-day period. Chronic oral treatment with the peripheral selective DβH inhibitor etamicastat (30 mg/kg/day) was performed in another cohort of SHR. RDN and chronic oral treatment with etamicastat did not affect renal function, as assessed by urinary protein, creatinine and urea levels. RDN significantly decreased mean arterial blood pressure (MAP, in mm H...
ABSTRACT Introduction Eating disorders (ED) like anorexia nervosa (AN), bulimia nervosa (BN) and ... more ABSTRACT Introduction Eating disorders (ED) like anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED) have complex psychopathological manifestation most presumably with a multifactor etiology. Abnormal feeding had long been linked to disruptions in brain dopaminergic activity. In humans, dopamine (DA) release in the dorsal striatum regulates feeding behavior and correlates with the degree of pleasure experienced while eating. Lower availability of DA could contribute to appetite dysregulation, binge eating behavior and lack of pleasure connected with meals. DA is metabolized, amongst others, by catechol-O-methyltransferase (COMT). Previous studies found an association between eating disorders and functional polymorphisms of COMT gene. Objectives To evaluate soluble COMT activity in erythrocytes from patients with anorexia, bulimia and binge eating disorders. Diagnostic was made by a senior psychiatry using the Structured Clinical Interview for DSM-IV Axis I disorders and Eating Disorder Examination Questionnaire. Results Erythrocyte COMT activity (in pmol/mg prot/h) is significantly increased in AN and BN patients (35.9±6.8 and 39.8±8.2, respectively) compared to the control group (21.2±3.6). In BED patients, COMT activity was also found higher, but due to a high variation between individual results are not significant (35.2±15.4). An interest result was also found in a group of patients with AN and BN that were being treated with a selective serotonin reuptake inhibitor (SSRI). Unexpectedly these patients presented a COMT activity level similar to the control levels. Conclusions Patients with AN and BN present higher soluble COMT activity in erythrocytes. This increase is reversed by treatment and SSRI.
Loss of salt-inducible kinase 1 (SIK1) triggers an increase in blood pressure (BP) upon a chronic... more Loss of salt-inducible kinase 1 (SIK1) triggers an increase in blood pressure (BP) upon a chronic high-salt intake in mice (Circ Res 2015;116:642-52). Here, we address possible acute mechanisms that may relate to the observed high BP in mice lacking SIK1. SIK1 knockout ( sik1 -/- ) and wild-type ( sik1 +/+ ) littermate mice were challenged for seven days with a normal- (0.3% NaCl) or high-salt (8% NaCl) diet. Systolic BP (SBP) was significantly increased in sik1 -/- mice (137.0±17.2 mmHg) after seven days of high-salt intake, as compared to sik1 +/+ mice counterparts (120.6±4.5 mmHg). The renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) were assayed in order to investigate the possible causes for the increase in SBP in sik1 -/- mice fed a high-salt diet. No differences in renin (normal-salt: 463.4±17.9, high-salt: 462.9±28.9 pg/ml) and angiotensin II (normal-salt: 45.8±10.0, high-salt: 39.0±8.5 pg/ml) serum levels were observed. The activity of dopamine β-hydr...
As the human ovarian follicle enlarges in the course of a regular cycle or following controlled o... more As the human ovarian follicle enlarges in the course of a regular cycle or following controlled ovarian stimulation, the changes in its structure reveal the oocyte environment composed of cumulus oophorus cells and the follicular fluid (FF).In contrast to the dynamic nature of cells, the fluid compartment appears as a reservoir rich in biomolecules. In some aspects, it is similar to the plasma, but it also exhibits differences that likely relate to its specific localization around the oocyte. The chemical composition indicates that the follicular fluid is able to detect and buffer excessive amounts of reactive oxygen species, employing a variety of antioxidants, some of them components of the intracellular milieu.An important part is played by albumin through specific cysteine residues. But the fluid contains other molecules whose cysteine residues may be involved in sensing and buffering the local oxidative conditions. How these molecules are recruited and regulated to intervene su...
Mice with targeted deletions of the α 2 -adrenoceptor genes were the first animal models lacking ... more Mice with targeted deletions of the α 2 -adrenoceptor genes were the first animal models lacking functional adrenoceptors. Deletion of the α 2C -receptor gene in mice has been reported in 1995 (Link et al., 1995), which was followed by α 2B - and α 2A -deficient mouse models in ...
This study investigates α2-adrenergic receptor (α2AR) mediated feedback inhibition of catecholami... more This study investigates α2-adrenergic receptor (α2AR) mediated feedback inhibition of catecholamine release from the adrenal medulla of adult (52 weeks) and old (98 weeks) spontaneously hypertensive rats (SHR) and normotensive controls Wistar Kyoto (WKY) rats. Adrenal epinephrine content as well as the spontaneous and the nicotinic-evoked release of epinephrine were similar between adult SHR and WKY rats. Aging produced a significant reduction in epinephrine synthesis in WKY rats. In contrast, in SHR aging produced a significant increase in epinephrine release without significant changes in epinephrine synthesis. The α2AR agonist medetomidine abolished (80–90% inhibition) the nicotinic-evoked release of epinephrine in adult SHR and WKY rats. With aging, this effect was unaltered in WKY rats but was significantly decreased in SHR (30% inhibition). Adrenal α2AAR mRNA levels were significantly reduced in old SHR compared with age matched WKY rats. In conclusion, in aging the α2AR mediated feedback inhibition of epinephrine release from the adrenal medulla is preserved in WKY rats but compromised in SHR, resulting in increased epinephrine release.
Aim: Statins, the mainstay in the treatment of hypercholesterolemia, are generally believed to ex... more Aim: Statins, the mainstay in the treatment of hypercholesterolemia, are generally believed to exert positive effects on CVD beyond their lipid lowering properties. Many studies have indicated that the anti-inflamma-tory effects of statins are in part responsible for this favorable influence. There are however no studies investigating how statins interact with the production of eicosanoids or other arachidonic acid (AA)-derived metab-olites in human vascular endothelial cells. Methods: Human umbilical endothelial cells were exposed to fluvasta-tin and analysed for expression of enzymes involved in the production of AA-derived metabolites using real time PCR and western blotting. The cellular formation of eicasanoids and NO were analysed by enzyme immunoassay. Moreover, the influence on the tone of resistance human arteries was assessed ex vivo. Results: A significant reduction of the expression of COX-1 mRNA after fluvastatin exposure was observed whereas mRNA expression specific fo...
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