21 results on '"Cicilini MA"'
Search Results
2. Evaluation of biological activities, structural and conformational properties of bovine beta- and alpha-trypsin isoforms in aqueous-organic media.
- Author
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Rosa DP, Cruz FT, Pereira EV, Cicilini MA, de Oliveira JS, Denadai ÂML, and Santos AMC
- Subjects
- Animals, Cattle, Hydrogen-Ion Concentration, Isoenzymes, Osmolar Concentration, Protein Structure, Secondary, Structure-Activity Relationship, Protein Aggregates, Trypsin chemistry
- Abstract
The study of the biological activity of trypsin isoforms in aqueous-organic media is of great interest to various fields of knowledge and biochemistry applications. Thus enzymatic, structural, and energetic properties of bovine β- and α-trypsin isoforms were compared in aqueous-organic media using 30 mg of each isoform. The results showed that the changes induced on the structure and activity of the same trypsin isoform occur at different concentrations. Better results for activity (ionic strength of 0.11 mol·L
-1 , at 37 °C and pH 8.0) were found in 0-40% of ethanolic media in which the activity for β-trypsin was about 60% higher than ɑ-trypsin. The ethanolic system does not cause significant changes in the level of secondary structure but the β-trypsin isoform undergoes a major rearrangement. The use of until 60% (v/v) ethanol showed that β-trypsin presents a denaturation process 17% more cooperative. The organic solvent causes redistribution in the supramolecular arrangement of both isoforms: all concentrations used induced the β-trypsin molecules to rearrange into agglomerates. The ɑ-trypsin rearranges into agglomerates up to 60% (v/v) of ethanol and aggregates at 80% (v/v) of ethanol. Both isoforms keep the enzymatic activity up to 60% (v/v) of ethanol., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2021
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3. The cannabinoid agonist WIN-2 affects acquisition but not consolidation of a spatial information in training and retraining processes: Relation with transcriptional regulation of the endocannabinoid system?
- Author
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Alarcon TA, Areal LB, Herlinger AL, Paiva KK, Cicilini MA, Martins-Silva C, and Pires RGW
- Subjects
- Animals, Cognitive Dysfunction metabolism, Hippocampus metabolism, Male, Mice, Prefrontal Cortex metabolism, Benzoxazines pharmacology, Cannabinoid Receptor Agonists pharmacology, Cognitive Dysfunction chemically induced, Endocannabinoids metabolism, Gene Expression Regulation drug effects, Hippocampus drug effects, Memory Consolidation drug effects, Memory, Short-Term drug effects, Morpholines pharmacology, Naphthalenes pharmacology, Prefrontal Cortex drug effects, Spatial Learning drug effects, Transcription, Genetic drug effects
- Abstract
The endocannabinoid system is capable of modulating multiple physiological brain functions including learning and memory. Moreover, there is evidence that the processes of acquisition and consolidation have distinct biological basis. We used the cannabinoid agonist WIN 55,212-2 (WIN-2) to investigate whether chronic CB1 activation affects acquisition and consolidation differently by evaluating gene expression in the hippocampus (HIP) and prefrontal cortex (PFC). Swiss mice were treated with WIN-2 (2 mg/kg) and submitted to the Morris water maze to evaluate different aspects of memory. We observed short-term memory impairment in acquisition of the spatial task while consolidation remained unchanged. In the PFC, animals that received WIN-2 prior to the task exhibited increased expression of the 2-AG synthesis enzyme diacylglycerol lipase and decreased levels of the degradation enzyme monoacylglycerol lipase, while mice that were treated after the task for the evaluation of consolidation exhibited the opposite profile. With respect to genes related to AEA metabolism, no correlation between the molecular and behavioral data could be established. In this sense, the cognitive impairment in the acquisition promoted by WIN-2 treatment may be related to a possible increase in the concentration of 2-AG in the PFC. Overall, this study confirms the relevance of the endocannabinoid system in the modulation of cognitive processes. A better understanding of the mechanisms underlying endocannabinoids roles in cognition could provide guidance for the development of treatments to reduce the cognitive deficits caused by drug abuse., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2020
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4. Atropine counteracts the depressive-like behaviour elicited by acute exposure to commercial chlorpyrifos in rats.
- Author
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Siqueira AA, Cunha AF, Marques GLM, Felippe ISA, Minassa VS, Gramelich TCDS, Cicilini MA, Alarcon TA, Pires RGW, Sampaio KN, and Beijamini V
- Subjects
- Acetylcholinesterase metabolism, Animals, Antidotes administration & dosage, Atropine administration & dosage, Behavior, Animal drug effects, Brain enzymology, Depression chemically induced, Dose-Response Relationship, Drug, Drug Therapy, Combination, Male, Organophosphate Poisoning etiology, Pralidoxime Compounds administration & dosage, Pralidoxime Compounds pharmacology, Rats, Rats, Wistar, Antidotes pharmacology, Atropine pharmacology, Brain drug effects, Chlorpyrifos toxicity, Depression prevention & control, Organophosphate Poisoning prevention & control
- Abstract
Acute organophosphate (OP) poisoning induces well-known signs of toxicosis related to acetylcholinesterase (AChE) inhibition. However, the relationship between acute OP poisoning and the onset of psychiatric disorders remains unclear. Thus, we investigated behavioural and biochemical consequences of acute exposure to the OP chlorpyrifos in male rats and also the effectiveness of the antidotes atropine and pralidoxime on reversing these changes. A sub-lethal dose of commercial chlorpyrifos (20 mg/kg, i.p.) elicited signs of acute toxicosis during the first hours after its injection in rats. Twenty-four hours after treatment, this single dose of chlorpyrifos induced a depressive-like behaviour in the rat forced swimming test without impairing locomotor activity. At this time (24 h), chlorpyrifos decreased plasma butyrylcholinesterase (BChE) activity and hippocampal, striatal and prefrontal cortical AChE activity in rats. The behavioural and biochemical consequences of acute chlorpyrifos poisoning do not seem to be long lasting, since 30 days later they were absent. We evaluated whether these behavioural and biochemical consequences of acute chlorpyrifos treatment would be reversed by the antidotes atropine (10 mg/kg i.p.) and/or pralidoxime (40 mg/kg; i.p.) given 1 h after poisoning. Pralidoxime partially reactivated the AChE activity in the prefrontal cortex, but not in the hippocampus and striatum. Atropine attenuated the depressive-like behaviour induced by chlorpyrifos in rats. Our results suggest that acute chlorpyrifos poisoning induces a transient depressive-like behaviour possible related to hippocampal AChE inhibition. They suggest that treatment with atropine and pralidoxime seems to be insufficient to counteract all the effects of OP acute poisoning, at least in rats., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2019
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5. Determination of structural and thermodynamic parameters of bovine α-trypsin isoform in aqueous-organic media.
- Author
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Rosa DP, Pereira EV, Vasconcelos AVB, Cicilini MA, da Silva AR, Lacerda CD, de Oliveira JS, Santoro MM, Coitinho JB, and Santos AMC
- Subjects
- Animals, Biocatalysis, Cattle, Dose-Response Relationship, Drug, Enzyme Stability drug effects, Isoenzymes chemistry, Isoenzymes metabolism, Protein Structure, Secondary, Thermodynamics, Ethanol pharmacology, Trypsin chemistry, Trypsin metabolism, Water chemistry
- Abstract
The α-trypsin isoform is a globular protein that belongs to serine-protease family and has a polypeptide chain of 223 amino acid residues, six disulfide bridges and two domains with similar structures. The effects of aqueous-organic solvent (ethanol) in different concentration on the α-trypsin structure have been investigated by spectroscopic techniques and thermodynamic data analysis. The results from spectroscopic measurements, including far-UV Circular Dichroism, UV-vis absorption spectroscopy, intrinsic tryptophan fluorescence and dynamic light scattering (DLS) suggest the formation of partially folded states, instead of aggregate states, at high ethanol concentration (>60% v/v ethanol), with little loss of secondary structure, but with significant tertiary structure changes. The thermodynamic data (T
m and ΔH) suggest a loosening of intramolecular weak interactions, which reflects in a flexibility increase such that the catalytic capacity can be increased or decreased according to the ethanol concentration into the system. Overall results we suggest that in range of 0-60% v/v ethanol/buffer, α-trypsin undergoes reversible multimerization phenomena with catalytic activity. However from 60% v/v ethanol/buffer, population of folded partially states with less catalytic activity are predominant., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2017
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6. Behavioural, biochemical and molecular changes induced by chronic crack-cocaine inhalation in mice: The role of dopaminergic and endocannabinoid systems in the prefrontal cortex.
- Author
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Areal LB, Rodrigues LC, Andrich F, Moraes LS, Cicilini MA, Mendonça JB, Pelição FS, Nakamura-Palacios EM, Martins-Silva C, and Pires RG
- Subjects
- Administration, Inhalation, Animals, Crack Cocaine administration & dosage, Dopamine genetics, Endocannabinoids genetics, Male, Mice, Mice, Inbred C57BL, Prefrontal Cortex drug effects, Behavior, Animal drug effects, Cocaine-Related Disorders metabolism, Crack Cocaine pharmacology, Dopamine metabolism, Endocannabinoids metabolism, Gene Expression Regulation drug effects, Motor Activity drug effects, Prefrontal Cortex metabolism
- Abstract
Crack-cocaine addiction has increasingly become a public health problem worldwide, especially in developing countries. However, no studies have focused on neurobiological mechanisms underlying the severe addiction produced by this drug, which seems to differ from powder cocaine in many aspects. This study investigated behavioural, biochemical and molecular changes in mice inhaling crack-cocaine, focusing on dopaminergic and endocannabinoid systems in the prefrontal cortex. Mice were submitted to two inhalation sessions of crack-cocaine a day (crack-cocaine group) during 11 days, meanwhile the control group had no access to the drug. We found that the crack-cocaine group exhibited hyperlocomotion and a peculiar jumping behaviour ("escape jumping"). Blood collected right after the last inhalation session revealed that the anhydroecgonine methyl ester (AEME), a specific metabolite of cocaine pyrolysis, was much more concentrated than cocaine itself in the crack-cocaine group. Most genes related to the endocannabinoid system, CB1 receptor and cannabinoid degradation enzymes were downregulated after 11-day crack-cocaine exposition. These changes may have decreased dopamine and its metabolites levels, which in turn may be related with the extreme upregulation of dopamine receptors and tyrosine hydroxylase observed in the prefrontal cortex of these animals. Our data suggest that after 11 days of crack-cocaine exposure, neuroadaptive changes towards downregulation of reinforcing mechanisms may have taken place as a result of neurochemical changes observed on dopaminergic and endocannabinoid systems. Successive changes like these have never been described in cocaine hydrochloride models before, probably because AEME is only produced by cocaine pyrolysis and this metabolite may underlie the more aggressive pattern of addiction induced by crack-cocaine., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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7. Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney.
- Author
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Graceli JB, Cicilini MA, Bissoli NS, Abreu GR, and Moysés MR
- Subjects
- Animals, Body Weight physiology, Catecholamines blood, Denervation, Female, Glomerular Filtration Rate physiology, Kidney metabolism, Ovariectomy, Rats, Wistar, Water-Electrolyte Balance physiology, Catecholamines metabolism, Chlorine metabolism, Estrogens physiology, Kidney innervation, Progesterone physiology, Sodium metabolism
- Abstract
The maintenance of extracellular Na+ and Cl- concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na+ and Cl- reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg · kg(-1) · day(-1), sc) and progesterone (OVP, 1.7 mg · kg(-1) · day(-1), sc). We assessed Na+ and Cl- fractional excretion (FENa+ and FECl- , respectively) and renal and plasma catecholamine release concentrations. FENa+ , FECl- , water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FENa+ , FECl- , water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6 ± 36.1 ng/g) and denervated rat groups (D: 102.1 ± 15.7; ODE: 108.7 ± 23.2; ODP: 101.1 ± 22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9 ± 25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function.
- Published
- 2013
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8. Influence of gender and estrous cycle on plasma and renal catecholamine levels in rats.
- Author
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Gomes HL, Graceli JB, Gonçalves WL, dos Santos RL, Abreu GR, Bissoli NS, Pires JG, Cicilini MA, and Moysés MR
- Subjects
- Animals, Chlorides urine, Dose-Response Relationship, Drug, Estradiol administration & dosage, Estradiol pharmacology, Female, Gonadal Hormones administration & dosage, Gonadal Hormones pharmacology, Kidney drug effects, Kidney physiopathology, Male, Nandrolone administration & dosage, Nandrolone analogs & derivatives, Nandrolone pharmacology, Nandrolone Decanoate, Orchiectomy methods, Orchiectomy statistics & numerical data, Ovariectomy methods, Ovariectomy statistics & numerical data, Progesterone administration & dosage, Progesterone pharmacology, Rats, Rats, Wistar, Sex Characteristics, Sodium urine, Urination drug effects, Urination physiology, Catecholamines blood, Catecholamines metabolism, Estrous Cycle blood, Estrous Cycle metabolism, Kidney metabolism
- Abstract
Several studies have demonstrated that gonadal hormones show significant effects on the brain and signaling pathways of effector organs/cells that respond to neurotransmitters. Since little information is available concerning the impact of male and female gonadal hormones on the renal and peripheral sympathetic system, the objective of this study was to further assess whether and how the renal content and plasma concentration of catecholamines are influenced by gender and the estrous cycle in rats. To achieve this, males Wistar rats were divided into 4 groups: (i) sham (i.e., control), (ii) gonadectomized, (iii) gonadectomized and nandrolone decanoate replacement at physiological levels or (iv) gonadectomized and nandrolone decanoate replacement at high levels. Female Wistar rats were divided into 6 groups: (i) ovariectomized (OVX), (ii) estrogen replacement at physiological levels and (iii) estrogen replacement at at high levels, (iv) progesterone replacement at physiological levels and (v) progesterone replacement at at high levels, and (vi) sham. The sham group was subdivided into four subgroups: (i) proestrus, (ii) estrus, (iii) metaestrus, and (iv) diestrus. Ten days after surgery, the animals were sacrificed and their plasma and renal catecholamine levels measured for intergroup comparisons. Gonadectomy led to an increase in the plasma catecholamine concentration in females, as well as in the renal catecholamine content of both male and female rats. Gonadectomized males also showed a lower level of plasma catecholamine than the controls. The urinary flow, and the fractional excretion of sodium and chloride were significantly increased in gonadectomized males and in the OVX group when compared with their respective sham groups.
- Published
- 2012
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9. Ultrasound lipoclasia on subcutaneous adipose tissue to produce acute hyperglycemia and enhance acute inflammatory response in healthy female rats.
- Author
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Gonçalves WL, Graceli JB, Santos RL, Cicilini MA, Bissoli NS, Abreu GR, and Moysés MR
- Subjects
- Animals, Blood Glucose metabolism, Body Composition, Body Mass Index, C-Reactive Protein analysis, Electric Impedance, Female, L-Lactate Dehydrogenase blood, Lipids blood, Rats, Rats, Wistar, Hyperglycemia etiology, Inflammation Mediators metabolism, Lipectomy adverse effects, Lipectomy methods, Subcutaneous Fat surgery, Ultrasonic Therapy adverse effects
- Abstract
Background: Ultrasound lipoclasia (USL) on white adipose tissue (WAT) has been largely used in the treatment of cellulite. Nevertheless, the acute consequences of this therapy on metabolism and biochemical profile are significant and should be taken into account., Objectives: To analyze the acute metabolic effects of USL in WAT of healthy rats using analyses of body composition, biochemical profile, and inflammatory markers., Methods: Female Wistar rats weighing approximately 250 g were divided into two groups (n=10 each): control and treated. The treated group was submitted to USL, a single 3-MHz ultrasound application (5.6 W/cm(2)), in gluteal-femoral WAT (3 cm(2)) for 3 minutes. Animals were subjected to glycemic control. Body composition was analyzed using bio-impedance, and lipid profile, insulinemia, C-reactive protein (CRP), and lactate dehydrogenase (LDH) were measured., Results: USL reduced (p<.05) body fat mass. The basal metabolic rate was found to have increased (p<.05). Basal insulin and the lipoprotein profile were not different, although the glycemic curve and CRP and LDH (p<.05) levels were higher., Conclusions: Fat mobilization using USL provokes acute hyperglycemia and enhances an acute inflammatory response, producing cardiometabolic risk in female rats.
- Published
- 2009
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10. Activity of angiotensin-converting enzyme after treatment with L-arginine in renovascular hypertension.
- Author
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Gouvea SA, Bissoli NS, Moysés MR, Cicilini MA, Pires JG, and Abreu GR
- Subjects
- Animals, Blood Pressure drug effects, Blood Pressure physiology, Disease Models, Animal, Male, Nitric Oxide metabolism, Rats, Rats, Wistar, Renin-Angiotensin System drug effects, Renin-Angiotensin System physiology, Surgical Instruments, Arginine pharmacology, Hypertension, Renal drug therapy, Hypertension, Renal metabolism, Peptidyl-Dipeptidase A metabolism
- Abstract
The renin-angiotensin system plays a role in the pathophysiology of renovascular hypertension. In addition, some studies have demonstrated a beneficial effect of L-arginine (L-Arg), the precursor of nitric oxide (NO), in this model of hypertension. This study was designed to investigate the effects of L-Arg on cardiovascular parameters and on the activity of the angiotensin-converting enzyme (ACE), after 14 days of renovascular hypertension. The experiments were performed on conscious male Wistar rats. Two-kidney, one-clip renovascular hypertension (2KIC) was initiated in rats by clipping the left renal artery during 14 days, while control rats were sham-operated. One group was submitted to a similar procedure and treated with L-Arg (10 mg/ml; average intake of 300mg/day) from the 7th to the 14th day after surgery, whereas the respective control group received water instead. At the end of the treatment period, the mean arterial pressure (MAP) was measured in conscious animals. The rats were sacrificed and the ACE activity was assayed in heart and kidneys, using Hip-His-Leu as substrate. In a separate group, the heart was removed, the left ventricle (LV) was weighed and the LV/body weight ratios (LV/BW) were determined. We observed significant differences in MAP between the L-Arg-treated and untreated groups (129 +/- 7 vs. 168 +/- 6 mmHg; P< 0.01). The cardiac hypertrophy described for this model of hypertension was attenuated in the 2K1C-L-Arg-treated group (14th day, wet LV/BW: 2K1C-L-Arg = 1.88 +/- 0.1; 2K1C = 2.20 +/- 0.1 mg/g; P < 0.05). L-Arg administration caused an important decrease in cardiac ACE activity (2K1C-L-Arg: 118 +/- 15; 2K1C: 266 +/- 34 micromol/min/mg; P < 0.01). L-Arg also decreased the ACE activity in the clipped kidney by 47% (P < 0.01), but not in the nonclipped kidney. These data suggest that increased NO formation and reduced angiotensin II formation are involved in the anthihypertensive effect of orally administered L-arginine.
- Published
- 2004
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11. The diuretic chlorthalidone normalizes baroreceptor and Bezold-Jarisch reflexes in DOCA-salt hypertensive rats.
- Author
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Bissoli NS, Cicilini MA, Vasquez EC, and Cabral AM
- Subjects
- Animals, Atrial Natriuretic Factor metabolism, Biguanides pharmacology, Blood Pressure drug effects, Desoxycorticosterone, Heart Rate drug effects, Hypertension chemically induced, Male, Myocardium metabolism, Potassium metabolism, Rats, Rats, Wistar, Serotonin Receptor Agonists pharmacology, Sodium metabolism, Baroreflex drug effects, Chlorthalidone pharmacology, Diuretics pharmacology, Hypertension physiopathology, Pressoreceptors drug effects
- Abstract
The contributions of arterial baroreceptor and Bezold-Jarisch reflexes, and atrial natriuretic factor (ANF) to the anti-hypertensive effect of the diuretic chlorthalidone were investigated in rats with deoxycorticosterone acetate (DOCA)-salt-induced hypertension. Chlorthalidone (8 mg rat(-1)day(-1)added to food) was given to one group during all 20 days of DOCA (8 mg kg(-1)s.c. twice per week) administration (preventive regimen) and, to another group, 20 days after DOCA treatment was initiated until the 40th day (therapeutic regimen). DOCA caused a significant increase in mean arterial pressure, reduced arterial baroreflex, and increased both the Bezold-Jarisch reflex and pro-ANF converting enzyme activity. Chlorthalidone reversed or prevented the DOCA-salt-induced hypertension, which was accompanied by the normalization of both the arterial baroreflex and the Bezold-Jarisch reflex. Additionally, both preventive and therapeutic regimens with chlorthalidone did cause normalization of the plasma sodium concentration and pro-ANF converting enzyme activity in the left atrium that follows DOCA-salt hypertension. Although it is difficult to determine the relative importance of each of the above regulatory mechanisms altered by chlorthalidone treatment, these data indicate that they may account for the prevention or decrease of DOCA-salt-induced hypertension in rats., (Copyright 2000 Academic Press.)
- Published
- 2000
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12. Differential effects of isoproterenol on the activity of angiotensin-converting enzyme in the rat heart and aorta.
- Author
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Busatto VC, Cunha V, Cicilini MA, and Mill JG
- Subjects
- Angiotensin II metabolism, Angiotensin-Converting Enzyme Inhibitors metabolism, Animals, Heart Atria drug effects, Heart Ventricles drug effects, Male, Plasma drug effects, Rats, Rats, Wistar, Adrenergic beta-Agonists pharmacology, Aorta drug effects, Aorta enzymology, Isoproterenol pharmacology, Myocardium enzymology, Renin-Angiotensin System drug effects, Renin-Angiotensin System physiology
- Abstract
The excessive stimulation of beta-adrenergic receptors in the heart induces myocardial hypertrophy. There are several experimental data suggesting that this hypertrophy may also depend, at least partially, on the increase of local production of angiotensin II secondary to the activation of the cardiac renin-angiotensin system. In this study we investigated the effects of isoproterenol on the activity of angiotensin-converting enzyme (ACE) in the heart and also in the aorta and plasma. Male Wistar rats weighing 250 to 305 g were treated with a dose of (+/-)-isoproterenol (0.3 mg kg-1 day-1, N = 8) sufficient to produce cardiac hypertrophy without deleterious effects on the pumping capacity of the heart. Control rats (N = 7) were treated with vehicle (corn oil). The animals were killed one week later. ACE activity was determined in vitro in the four cardiac chambers, aorta and plasma by a fluorimetric assay. A significant hypertrophy was observed in both ventricular chambers. ACE activity in the atria remained constant after isoproterenol treatment. There was a significant increase (P < 0.05) of ACE activity in the right ventricle (6.9 +/- 0.9 to 8.2 +/- 0.6 nmol His-Leu g-1 min-1) and in the left ventricle (6.4 +/- 1.1 to 8.9 +/- 0.8 nmol His-Leu g-1 min-1). In the aorta, however, ACE activity decreased (P < 0.01) after isoproterenol (41 +/- 3 to 27 +/- 2 nmol His-Leu g-1 min-1) while it remained unchanged in the plasma. These data suggest that ACE expression in the heart can be increased by stimulation of beta-adrenoceptors. However, this effect is not observed on other local renin-angiotensin systems, such as the aorta. Our data also suggest that the increased sympathetic discharge and the elevated plasma concentration of catecholamines may contribute to the upregulation of ACE expression in the heart after myocardial infarction and heart failure.
- Published
- 1999
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13. Increased angiotensin-converting enzyme activity in the left ventricle after infarction.
- Author
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Busatto VC, Cicilini MA, and Mill JG
- Subjects
- Angiotensin II metabolism, Animals, Blood Pressure physiology, Body Weight physiology, Heart Rate physiology, Male, Rats, Rats, Wistar, Renin-Angiotensin System physiology, Heart Ventricles enzymology, Myocardial Infarction enzymology, Peptidyl-Dipeptidase A metabolism
- Abstract
An increase in angiotensin-converting enzyme (ACE) activity has been observed in the heart after myocardial infarction (MI). Since most studies have been conducted in chronically infarcted individuals exhibiting variable degrees of heart failure, the present study was designed to determine ACE activity in an earlier phase of MI, before heart failure development. MI was produced in 3-month old male Wistar rats by ligation of the anterior branches of the left coronary artery, control rats underwent sham surgery and the animals were studied 7 or 15 days later. Hemodynamic data obtained for the anesthetized animals showed normal values of arterial blood pressure and of end-diastolic pressure in the right and left ventricular cavities of MI rats. Right and left ventricular (RV, LV) muscle and scar tissue homogenates were prepared to determine ACE activity in vitro by measuring the velocity of His-Leu release from the synthetic substrate Hyp-His-Leu. ACE activity was corrected to the tissue wet weight and is reported as nmol His-Leu g-1 min-1. No significant change in ACE activity in the RV homogenates was demonstrable. A small nonsignificant increase of ACE activity (11 +/- 9%; P > 0.05) was observed 7 days after MI in the surviving left ventricular muscle. Two weeks after surgery, however, ACE activity was 46 +/- 11% (P < 0.05) higher in infarcted rats compared to sham-operated rats. The highest ACE activity was demonstrable in the scar tissue homogenate. In rats studied two weeks after surgery, ACE activity in the LV muscle increased from 105 +/- 7 nmol His-Leu g-1 min-1 in control hearts to 153 +/- 11 nmol His-Leu g-1 min-1 (P < 0.05) in the remaining LV muscle of MI rats and to 1051 +/- 208 nmol His-Leu g-1 min-1 (P < 0.001) in the fibrous scar. These data indicate that ACE activity increased in the heart after infarction before heart failure was demonstrable by hemodynamic measurements. Since the blood vessels of the scar drain to the remaining LV myocardium, the high ACE activity present in the fibrous scar may increase the angiotensin II concentration and decrease bradykinin in the cardiac tissues surrounding the infarcted area. The increased angiotensin II in the fibrous scar may contribute to the reactive fibrosis and hypertrophy in the left ventricular muscle surviving infarction.
- Published
- 1997
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14. Evaluation of protein and peptide hydrolases in DOCA-salt hypertensive rat treated with chlorthalidone.
- Author
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Santos-Costa JL, Bissoli NS, Cabral AM, and Cicilini MA
- Subjects
- Animals, Hypertension chemically induced, Male, Rats, Rats, Wistar, Antihypertensive Agents therapeutic use, Chlorthalidone therapeutic use, Desoxycorticosterone administration & dosage, Hypertension enzymology, Hypertension therapy, Peptide Hydrolases metabolism
- Abstract
We have reported that chlorthalidone (Chlor) prevents the development of heart hypertrophy in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The present study was carried out to determine whether Chlor (8 mg/day per animal, added to the food, for 20 days) affects kidney and heart hypertrophy in DOCA-salt (8 mg/kg, sc, twice a week) rats by causing alterations in protein and peptide hydrolysis. Heart (left ventricle) and kidney enzyme activities were measured in tissue homogenates from normal-control, salt-control, DOCA-salt and DOCA-salt-Chlor male Wistar rats (N = 6 for each group), using azocasein as the substrate for proteolytic enzymes and specific peptides for prolylendopeptidase (PEP) and multicatalytic proteinase (MCP). The tissue weight/body weight ratio increased in parallel to elevation of blood pressure. The left ventricular muscle hypertrophy (26%, P < 0.05) present in the DOCA-salt hypertensive group was completely prevented by simultaneous Chlor treatment. Chlor treatment did not change the kidney hypertrophy (+79%, P < 0.;05) observed in the salt-control (+57%, P < 0.05) and DOCA-salt (+74%, P < 0.05) groups. The hydrolysis of peptides by PEP and MCP was similar in the normal and salt-control groups. The heart PEP activity was 24% higher (P < 0.01) in DOCA-salt rats, whereas MCP activity was not different when compared to control groups. DOCA-salt treatment increased MCP activity in the kidney by 44% while PEP activity did not differ from that of control groups. The hydrolysis of proteins by heart enzymes was increased by salt by 47%. Chlor treatment restored the reduction in protein hydrolysis induced by DOCA-salt (a 21% decrease, P < 0.05) to a level similar to that of the normal-control group. Similarly, Chlor coadministration prevented the 30% reduction in renal proteolytic activity elicited by DOCA-salt treatment. Although Chlor treatment prevented the DOCA-salt-induced reduction in protein hydrolysis, this response did not interfere with kidney hypertrophy. The mechanism by which hypertension produces hypertrophy is unclear, but our results suggest that this structural modification is not related to the activities of some peptidases, e.g. protein and peptide hydrolases.
- Published
- 1996
15. Calpain activity of hypertrophic hearts from hypertensive rats.
- Author
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Cicilini MA, Resende MM, Bissoli NS, Vasquez EC, and Cabral AM
- Subjects
- Animals, Desoxycorticosterone administration & dosage, Male, Protein Denaturation drug effects, Rats, Rats, Inbred SHR, Rats, Wistar, Tissue Extracts physiology, Calpain metabolism, Hypertrophy, Left Ventricular metabolism
- Abstract
Heart tissue contains large amounts of the Ca(2+)-activated proteinase calpain which has been assigned a specific function in the turnover of muscle protein. The objective of the present study was to determine calpain (E.C. 3.4.22.17)-like activity in homogenates of left ventricle from hypertensive rats that developed ventricular hypertrophy. Calpain activity was assayed using heat-denatured azocasein as a substrate in the presence of 1 mM calcium and corrected by subtraction of the Ca(2+)-independent activities. The latter were measured in the presence of 1 mM EGTA and the products read at 440 nm. Male Wistar rats (225 g) were assigned to control (N = 8, normal drinking water), salt (N = 6, drinking water containing 1% NaCl) and DOCA-salt (N = 6, deoxycorticosterone acetate, 8 mg/kg, sc, twice a week for 20 days plus drinking water containing 1% NaCl) groups. SHR (N = 6, spontaneously hypertensive rats) were also used. The calpain activity of the control group was at 3.90 +/- 0.22 mU/g wet weight tissue. Hypertension induced significant left ventricular hypertrophy in DOCA-salt rats (26%) and in SHR (54%) and a 30% decrease in calpain activity in both groups (P < 0.01). In the high salt load (salt group) calpain activity was also decreased, but this was not accompanied by hypertrophy. In the present indirect measurement of protein degradation capacity of heart tissue homogenates the proteolytic activity was activated (221%) by 1 mM calcium and inhibited (84%) by 1 mM EGTA after a 48-h incubation period, indicating the destruction of the calpain inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1995
16. Heart prolyl endopeptidase activity in one-kidney, one clip hypertensive rats.
- Author
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Cicilini MA, Ramos PS, Vasquez EC, and Cabral AM
- Subjects
- Analysis of Variance, Animals, Male, Prolyl Oligopeptidases, Rats, Rats, Wistar, Hypertension, Renovascular enzymology, Myocardium enzymology, Serine Endopeptidases metabolism
- Abstract
1. Heart mass, prolyl endopeptidase activity and fractionated proteins from heart tissue were studied in one-kidney, one clip hypertensive rats (N = 6) and compared to sham-operated rats (N = 6). 2. Body weight, arterial pressure and tissue mass were measured 4 weeks after artery clipping. Z-Gly-Pro-p-nitroaniline hydrolysis was used to measure tissue prolyl endopeptidase activity in the homogenate. Protein was fractionated into the soluble and myofibrillar fractions. 3. In the normotensive rats, prolyl endopeptidase activity expressed in terms of protein specific activity (microM substrate hydrolyzed h-1 mg supernatant protein-1) occurred in atria and was 2.5-fold higher than in the ventricles (3.79 +/- 0.20 vs 1.44 +/- 0.02, P < 0.05). In the one-kidney, one clip hypertensive rats, the left ventricle tissue increased 1.7-fold (2.27 +/- 0.11 vs 3.72 +/- 0.11 mg wet weight tissue/g body weight, P < 0.001), the soluble protein fraction (54.86 +/- 3.60 vs 57.38 +/- 6.64 mg/g wet weight tissue) was unchanged, while the myofibrillar fraction increased 1.9-fold (118.9 +/- 9.09 vs 229.8 +/- 8.47 mg/g wet weight tissue, P < 0.001). 4. The specific activity of the atrial and ventricular prolyl endopeptidase decreased in atria and increased in ventricles as the result of hypertension (3.79 +/- 0.2 vs 2.84 +/- 0.13 and 1.44 +/- 0.02 vs 1.87 +/- 0.13; respectively). These regional differences in prolyl endopeptidase enzyme content caused by one-kidney, one clip hypertension in neurosecretory and non-neurosecretory heart areas suggest that this enzyme plays a local role in the turnover of specific polypeptides.
- Published
- 1994
17. Effects of chlorthalidone on ventricular hypertrophy in deoxycorticosterone acetate-salt hypertensive rats.
- Author
-
Cabral AM, Carvalhinho FB, Vasquez EC, and Cicilini MA
- Subjects
- Animals, Blood Pressure drug effects, Body Weight drug effects, Cardiomegaly physiopathology, Desoxycorticosterone, Dose-Response Relationship, Drug, Heart Rate drug effects, Male, Rats, Rats, Wistar, Sodium, Dietary, Vagus Nerve drug effects, Vagus Nerve physiopathology, Cardiomegaly drug therapy, Cardiomegaly prevention & control, Chlorthalidone therapeutic use, Hypertension physiopathology
- Abstract
Diuretics have been the mainstay of long-term treatment of hypertension, but there is no evidence suggesting that diuretics may be effective in reducing cardiac hypertrophy associated with hypertension. Thus, the present study was carried out to elucidate if long-term treatment with chlorthalidone (8 mg per animal per day added to food) affects the development of and reverses the ventricular hypertrophy in deoxycorticosterone acetate (DOCA) (8 mg/kg SC twice a week)-salt hypertensive rats. Chlorthalidone was given to one group during all 20 days of DOCA administration (preventive regimen) and to another group 20 days after DOCA treatment was initiated until the 40th day (therapeutic regimen). Chlorthalidone was found to reduce or prevent the development of ventricular hypertrophy, as assessed by a reduction in ventricular mass and cardiac protein as well as arterial hypertension. Both chlorthalidone regimens prevented the increase or induced a significant decrease in the plasma concentration of sodium and in cardiac sympathetic tone, which were both increased in DOCA-salt-treated rats. These data provide evidence that long-term chlorthalidone treatment is effective in preventing or reducing ventricular hypertrophy along with arterial hypertension. However, whether this is due to a reduction in plasma sodium or other additional mechanisms, such as a reduction in cardiac sympathetic tone, remains to be determined.
- Published
- 1994
- Full Text
- View/download PDF
18. Inhibition of rabbit tissue kininase by anti-(endo-oligopeptidase A) antibodies.
- Author
-
Coelho HL, Cicilini MA, Carvalho KM, Carvalho IF, and Camargo AC
- Subjects
- Animals, Bradykinin metabolism, Brain enzymology, Immune Sera, Immunoelectrophoresis, Peptidyl-Dipeptidase A immunology, Rabbits, Tissue Distribution, Peptidyl-Dipeptidase A analysis
- Abstract
Highly purified rabbit brain endo-oligopeptidase A injected into goats produced, after 60 days of immunization, antisera that specifically inhibit purified rabbit brain endo-oligopeptidase A. An immunoreactive kininase having the same specificity as rabbit brain endo-oligopeptidase A for bradykinin was detected in several rabbit tissues. The highest amount of this immunoreactive kininase was found in the 25000 g supernatant fraction (S fraction) of heart, liver, skeletal muscle, ovary, brain and testis homogenates, corresponding to 89, 86, 78, 59, 56 and 53% respectively of the whole kininase activity found in the S fraction.
- Published
- 1981
- Full Text
- View/download PDF
19. Breakdown of biologically active peptides by brain endo-oligopeptidases (kininase A and B).
- Author
-
Camargo AC, Cicilini MA, and Carvalho KM
- Subjects
- Amino Acid Sequence, Animals, Rabbits, Brain enzymology, Cysteine Endopeptidases, Endopeptidases metabolism, Peptides metabolism, Peptidyl-Dipeptidase A metabolism
- Published
- 1983
20. Endooligopeptidase A activity in rabbit heart: generation of enkephalin from enkephalin containing peptides.
- Author
-
Cicilini MA, Ribeiro MJ, de Oliveira EB, Mortara RA, and de Camargo AC
- Subjects
- Amino Acid Sequence, Animals, Chromatography, DEAE-Cellulose, Chromatography, Gel, Cysteine Endopeptidases isolation & purification, Electrophoresis, Disc, Electrophoresis, Polyacrylamide Gel, Indicators and Reagents, Molecular Weight, Rabbits, Substrate Specificity, Cysteine Endopeptidases metabolism, Enkephalins biosynthesis, Metalloendopeptidases, Myocardium enzymology, Neuropeptides metabolism
- Abstract
Two endopeptidases displaying similar specificities towards peptide hormone substrates but differing in molecular size have been identified in rabbit heart and isolated by a combination of ion-exchange chromatography, gel filtration and preparative gel electrophoresis. These two enzymes share several properties with the previously described rabbit brain endooligopeptidase A. They were shown to produce, by a single peptide bond cleavage, [Met5] enkephalin and [Leu5]enkephalin from small enkephalin containing peptides. They also hydrolyze the Phe5-Ser5 bond of bradykinin and the Arg8-Arg9 bond of neurotensin. Characteristically, the activity of both low and high Mr enzymes is restricted to oligopeptides. Both forms of heart endooligopeptidase A are inhibited by antibodies raised against the brain enzyme. When electrophoresed in SDS-polyacrylamide gel under denaturing conditions, the low Mr heart enzyme shows a major band of Mr = 73,000, comparable in size to the brain enzyme. The SDS-PAGE of the high and low Mr enzymes analyzed by immunoblotting with an antibody raised against low Mr brain endooligopeptidase A, showed a major antigen band corresponding to Mr = 72,000. In addition, immunoblotting has also demonstrated that a monoclonal antibody antitubulin reacts with a polypeptide corresponding to Mr = 50,000 present in the purified high Mr endooligopeptidase A. Both enzymes are activated by dithiothreitol and inhibited by thiol reagents, but are not affected by leupeptin, DFP or EDTA, thus indicating that they should be classified as nonlysosomal cysteinyl-endooligopeptidase A.
- Published
- 1988
- Full Text
- View/download PDF
21. Rabbit tissue peptidases that hydrolyse the peptide hormone bradykinin. Differences in enzymic properties and concentration in rabbit tissues.
- Author
-
Cicilini MA, Caldo H, Berti JD, and Camargo AC
- Subjects
- Amino Acids analysis, Animals, Dithiothreitol pharmacology, Edetic Acid pharmacology, Peptide Fragments analysis, Peptides pharmacology, Rabbits, Zinc pharmacology, Bradykinin metabolism, Peptidyl-Dipeptidase A metabolism
- Abstract
The distribution and properties of neutral peptidases acting on the peptide hormone bradykinin (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) were determined in several rabbit tissues. The supernatant and particulate fractions prepared from tissue homogenates (25000g for 60min) were studied. Bradykinin inactivation (kininase activity) was measured by bioassay with the isolated guinea-pig ileum. The sites of peptide-bond cleavage were determined in the amino acid analyser, which permits detection and measurement of amino acids and peptides derived from bradykinin. The results indicate that kininases are present in a wide range of concentrations in different tissues, kidney and lung having the most activity. Kininases present in different tissues were distinguished on the basis of sensitivity to the effects of EDTA, dithiothreitol and ZnCl2 and by the site of peptide-bond hydrolysis in bradykinin.
- Published
- 1977
- Full Text
- View/download PDF
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