MARIA CLAUDIA COSTA IRIGOYEN
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/59 - Laboratório de Biologia Celular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/65, Hospital das Clínicas, Faculdade de Medicina
LIM/59 - Laboratório de Biologia Celular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/65, Hospital das Clínicas, Faculdade de Medicina
10 resultados
Resultados de Busca
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- Sildenafil preserves diastolic relaxation after reduction by L-NAME and increases phosphodiesterase-5 in the intercalated discs of cardiac myocytes and arterioles(2011) FERREIRA-MELO, Silvia Elaine; DEMACQ, Caroline; LACCHINI, Silvia; KRIEGER, Jose Eduardo; IRIGOYEN, Maria Claudia; MORENO, HeitorOBJECTIVES: We investigated the influence of sildenafil on cardiac contractility and diastolic relaxation and examined the distribution of phosphodiesterase-5 in the hearts of hypertensive rats that were treated with by NG-nitro-L-arginine methyl ester (L-NAME). METHODS: Male Wistar rats were treated with L-NAME and/or sildenafil for eight weeks. The Langendorff method was used to examine the effects of sildenafil on cardiac contractility and diastolic relaxation. The presence and location of phosphodiesterase-5 and phosphodiesterase-3 were assessed by immunohistochemistry, and cGMP plasma levels were measured by ELISA. RESULTS: In isolated hearts, sildenafil prevented the reduction of diastolic relaxation (dP/dt) that was induced by L-NAME. In addition, phosphodiesterase-5 immunoreactivity was localized in the intercalated discs between the myocardial cells. The staining intensity was reduced by L-NAME, and sildenafil treatment abolished this reduction. Consistent with these results, the plasma levels of cGMP were decreased in the L-NAME-treated rats but not in rats that were treated with L-NAME + sildenafil. CONCLUSION: The sildenafil-induced attenuation of the deleterious hemodynamic and cardiac morphological effects of L-NAME in cardiac myocytes is mediated (at least in part) by the inhibition of phosphodiesterase-5.
- ACE gene dosage determines additional autonomic dysfunction and increases renal angiotensin II levels in diabetic mice(2018) MORAES, Oscar Albuquerque de; FLUES, Karin; SCAPINI, Katie Bilhar; MOSTARDA, Cristiano; EVANGELISTA, Fabiana de Sant'Anna; RODRIGUES, Bruno; DARTORA, Daniela Ravizzoni; FIORINO, Patricia; ANGELIS, Katie De; IRIGOYEN, Maria ClaudiaOBJECTIVES: The present study aimed to investigate cardiovascular autonomic modulation and angiotensin II (Ang II) activity in diabetic mice that were genetically engineered to harbor two or three copies of the angiotensin-converting enzyme gene. METHODS: Diabetic and non-diabetic mice harboring 2 or 3 copies of the angiotensin-converting enzyme gene were used in the present study. Animals were divided into 4 groups: diabetic groups with two and three copies of the angiotensin-converting enzyme gene (2CD and 3CD) and the respective age-matched non-diabetic groups (2C and 3C). Hemodynamic, cardiovascular, and autonomic parameters as well as renal Ang II expression were evaluated. RESULTS: Heart rate was lower in diabetic animals than in non-diabetic animals. Autonomic modulation analysis indicated that the 3CD group showed increased sympathetic modulation and decreased vagal modulation of heart rate variability, eliciting increased cardiac sympathovagal balance, compared with all the other groups. Concurrent diabetes and either angiotensin-converting enzyme polymorphism resulted in a significant increase in Ang II expression in the renal cortex. CONCLUSION: Data indicates that a small increase in angiotensin-converting enzyme activity in diabetic animals leads to greater impairment of autonomic function, as demonstrated by increased sympathetic modulation and reduced cardiac vagal modulation along with increased renal expression of Ang II.
- The impact of metabolic syndrome on metabolic, proinflammatory and prothrombotic markers according to the presence of high blood pressure criterion(2013) GIL, Juliana S.; DRAGER, Luciano F.; GUERRA-RICCIO, Grazia M.; MOSTARDA, Cristiano; IRIGOYEN, Maria C.; COSTA-HONG, Valeria; BORTOLOTTO, Luiz A.; EGAN, Brent M.; LOPES, Heno F.OBJECTIVES: We explored whether high blood pressure is associated with metabolic, inflammatory and prothrombotic dysregulation in patients with metabolic syndrome. METHODS: We evaluated 135 consecutive overweight/obese patients. From this group, we selected 75 patients who were not under the regular use of medications for metabolic syndrome as defined by the current Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults criteria. The patients were divided into metabolic syndrome with and without high blood pressure criteria (>= 130/>= 85 mmHg). RESULTS: Compared to the 45 metabolic syndrome patients without high blood pressure, the 30 patients with metabolic syndrome and high blood pressure had significantly higher glucose, insulin, homeostasis model assessment insulin resistance index, total cholesterol, low-density lipoprotein-cholesterol, triglycerides, uric acid and creatinine values; in contrast, these patients had significantly lower high-density lipoprotein-cholesterol values. Metabolic syndrome patients with high blood pressure also had significantly higher levels of retinol-binding protein 4, plasminogen activator inhibitor 1, interleukin 6 and monocyte chemoattractant protein 1 and lower levels of adiponectin. Moreover, patients with metabolic syndrome and high blood pressure had increased surrogate markers of sympathetic activity and decreased baroreflex sensitivity. Logistic regression analysis showed that high-density lipoprotein, retinol-binding protein 4 and plasminogen activator inhibitor-1 levels were independently associated with metabolic syndrome patients with high blood pressure. There is a strong trend for an independent association between metabolic syndrome patients with high blood pressure and glucose levels. CONCLUSIONS: High blood pressure, which may be related to the autonomic dysfunction, is associated with metabolic, inflammatory and prothrombotic dysregulation in patients with metabolic syndrome.
- Short-term diabetes attenuates left ventricular dysfunction and mortality rates after myocardial infarction in rodents(2011) RODRIGUES, Bruno; FIGUEROA, Diego Mendrot Taboas; FANG, Jiao; ROSA, Kaleizu Teodoro; LLESUY, Suzana; ANGELIS, Katia De; IRIGOYEN, Maria ClaudiaOBJECTIVES: To investigate the effects of hyperglycemia on left ventricular dysfunction, morphometry, myocardial infarction area, hemodynamic parameters, oxidative stress profile, and mortality rate in rats that had undergone seven days of myocardial infarction. INTRODUCTION: Previous research has demonstrated that hyperglycemia may protect the heart against ischemic injury. METHODS: Male Wistar rats were divided into four groups: control-sham, diabetes-sham, myocardial infarction, and diabetes + myocardial infarction. Myocardial infarction was induced 14 days after diabetes induction. Ventricular function and morphometry, as well as oxidative stress and hemodynamic parameters, were evaluated after seven days of myocardial infarction. RESULTS: The myocardial infarction area, which was similar in the infarcted groups at the initial evaluation, was reduced in the diabetes + myocardial infarction animals (23 +/- 3%) when compared with the myocardial infarction (42 +/- 7%, p<0.001) animals at the final evaluation. The ejection fraction (22%, p = 0.003), velocity of circumferential fiber shortening (30%, p = 0.001), and left ventricular isovolumetric relaxation time (26%, p = 0.002) were increased in the diabetes + myocardial infarction group compared with the myocardial infarction group. The diabetes-sham and diabetes + myocardial infarction groups displayed increased catalase concentrations compared to the control-sham and myocardial infarction groups (diabetes-sham: 32 +/- 3; diabetes + myocardial infarction: 35 +/- 0.7; control-sham: 12 +/- 2; myocardial infarction: 16 +/- 0.1 pmol min(-1) mg(-1) protein). The levels of thiobarbituric acid-reactive substances were reduced in the diabetes-sham rats compared to the control-sham rats. These positive adaptations were reflected in a reduced mortality rate in the diabetes + myocardial infarction animals (18.5%) compared with the myocardial infarction animals (40.7%, p = 0.001). CONCLUSIONS: These data suggest that short-term hyperglycemia initiates compensatory mechanisms, as demonstrated by increased catalase levels, which culminate in improvements in the ventricular response, infarcted area, and mortality rate in diabetic rats exposed to ischemic injury.
- Simvastatin-induced cardiac autonomic control improvement in fructose-fed female rats(2011) SILVA, Renata Juliana da; BERNARDES, Nathalia; BRITO, Janaina de O.; SANCHES, Iris Callado; IRIGOYEN, Maria Claudia; ANGELIS, Katia DeOBJECTIVE: Because autonomic dysfunction has been found to lead to cardiometabolic disorders and because studies have reported that simvastatin treatment has neuroprotective effects, the objective of the present study was to investigate the effects of simvastatin treatment on cardiovascular and autonomic changes in fructose-fed female rats. METHODS: Female Wistar rats were divided into three groups: controls (n = 8), fructose (n = 8), and fructose+simvastatin (n = 8). Fructose overload was induced by supplementing the drinking water with fructose (100 mg/L, 18 wks). Simvastatin treatment (5 mg/kg/day for 2 wks) was performed by gavage. The arterial pressure was recorded using a data acquisition system. Autonomic control was evaluated by pharmacological blockade. RESULTS: Fructose overload induced an increase in the fasting blood glucose and triglyceride levels and insulin resistance. The constant rate of glucose disappearance during the insulin intolerance test was reduced in the fructose group (3.4 +/- 0.32%/min) relative to that in the control group (4.4 +/- 0.29%/min). Fructose+simvastatin rats exhibited increased insulin sensitivity (5.4 +/- 0.66%/min). The fructose and fructose+simvastatin groups demonstrated an increase in the mean arterial pressure compared with controls rats (fructose: 124 +/- 2 mmHg and fructose+simvastatin: 126 +/- 3 mmHg vs. controls: 112 +/- 2 mmHg). The sympathetic effect was enhanced in the fructose group (73 +/- 7 bpm) compared with that in the control (48 +/- 7 bpm) and fructose+simvastatin groups (31 +/- 8 bpm). The vagal effect was increased in fructose+simvastatin animals (84 +/- 7 bpm) compared with that in control (49 +/- 9 bpm) and fructose animals (46 +/- 5 bpm). CONCLUSION: Simvastatin treatment improved insulin sensitivity and cardiac autonomic control in an experimental model of metabolic syndrome in female rats. These effects were independent of the improvements in the classical plasma lipid profile and of reductions in arterial pressure. These results support the hypothesis that statins reduce the cardiometabolic risk in females with metabolic syndrome.
- Effects of sympathectomy on myocardium remodeling and function(2021) JORDAO, Mauricio Rodrigues; PESSOA, Fernanda G.; FONSECA, Keila C. B.; ZANONI, Fernando; SALEMI, Vera M. C.; SOUZA, Leandro E.; RIBEIRO, Orlando N.; FERNANDES, Fabio; IRIGOYEN, Maria Claudia; MOREIRA, Luiz Felipe P.; MADY, Charles; RAMIRES, Felix Jose AlvarezOBJECTIVES: To evaluate the effects of sympathectomy on the myocardium in an experimental model. METHODS: The study evaluated three groups of male Wistar rats: control (CT; n=15), left unilateral sympathectomy (UNI; n=15), and bilateral sympathectomy (BIL; n=31). Sympathectomy was performed by injection of absolute alcohol into the space of the spinous process of the C7 vertebra. After 6 weeks, we assessed the chronotropic properties at rest and stress, cardiovascular autonomic modulation, myocardial and peripheral catecholamines, and beta-adrenergic receptors in the myocardium. The treadmill test consisted of an escalated protocol with a velocity increment until the maximal velocity tolerated by the animal was reached. RESULTS: The bilateral group had higher levels of peripheral catecholamines, and consequently, a higher heart rate (HR) and blood pressure levels. This suggests that the activation of a compensatory pathway in this group may have deleterious effects. The BIL group had basal tachycardia immediately before the exercise test and increased tachycardia at peak exercise (p<0.01); the blood pressure had the same pattern (p=0.0365). The variables related to autonomic modulation were not significantly different between groups, with the exception of the high frequency (HF) variable, which showed significant differences in CT vs UNI. There was no significant difference in beta receptor expression between groups. There was a higher concentration of peripheral norepinephrine in the BIL group (p=0.0001), and no significant difference in myocardial norepinephrine (p=0.09). CONCLUSION: These findings suggest that an extra cardiac compensatory pathway increases the sympathetic tonus and maintains a higher HR and higher levels of peripheral catecholamines in the procedure groups. The increase in HF activity can be interpreted as an attempt to increase the parasympathetic tonus to balance the greater sympathetic activity.
- Renal oxygen content is increased in healthy subjects after angiotensin-converting enzyme inhibition(2012) STEIN, Anna; GOLDMEIER, Silvia; VOLTOLINI, Sarah; SETOGUTTI, Enio; FELDMAN, Carlos; FIGUEIREDO, Eduardo; EICK, Renato; IRIGOYEN, Maria; RIGATTO, KatyaOBJECTIVE: The association between renal hypoxia and the development of renal injury is well established. However, no adequate method currently exists to non-invasively measure functional changes in renal oxygenation in normal and injured patients. METHOD: R2(star) quantification was performed using renal blood oxygen level-dependent properties. Five healthy normotensive women (50 +/- 5.3 years) underwent magnetic resonance imaging in a 1.5T Signa Excite HDx scanner (GE Healthcare, Waukesha, WI). A multiple fast gradient-echo sequence was used to acquire R2(star)/T-2(star) images (sixteen echoes from 2.1 ms/slice to 49.6 ms/slice in a single breath hold per location). The images were post-processed to generate R2(star) maps for quantification. Data were recorded before and at 30 minutes after the oral administration of an angiotensin II-converting enzyme inhibitor (captopril, 25 mg). The results were compared using an ANOVA for repeated measurements (mean +/- standard deviation) followed by the Tukey test. ClinicalTrials.gov: NCT01545479. RESULTS: A significant difference (p<0.001) in renal oxygenation (R2(star)) was observed in the cortex and medulla before and after captopril administration: right kidney, cortex = 11.08 +/- 0.56ms, medulla = 17.21 +/- 1.47ms and cortex = 10.30 +/- 0.44ms, medulla = 16.06 +/- 1.74ms, respectively; and left kidney, cortex = 11.79 +/- 1.85ms, medulla = 17.03 +/- 0.88ms and cortex = 10.89 +/- 0.91ms, medulla = 16.43 +/- 1.49ms, respectively. CONCLUSIONS: This result suggests that the technique efficiently measured alterations in renal blood oxygenation after angiotensin II-converting enzyme inhibition and that it may provide a new strategy for identifying the early stages of renal disease and perhaps new therapeutic targets.
- Exercise training prevents diastolic dysfunction induced by metabolic syndrome in rats(2012) MOSTARDA, Cristiano; MORAES-SILVA, Ivana Cinthya; SALEMI, Vera Maria Cury; MACHI, Jacqueline Freire; RODRIGUES, Bruno; ANGELIS, Katia De; FARAH, Vera de Moura Azevedo; IRIGOYEN, Maria ClaudiaOBJECTIVE: High fructose consumption contributes to the incidence of metabolic syndrome and, consequently, to cardiovascular outcomes. We investigated whether exercise training prevents high fructose diet-induced metabolic and cardiac morphofunctional alterations. METHODS: Wistar rats receiving fructose overload (F) in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) for 10 weeks or kept sedentary. These rats were compared with a control group (C). Obesity was evaluated by the Lee index, and glycemia and insulin tolerance tests constituted the metabolic evaluation. Blood pressure was measured directly (Windaq, 2 kHz), and echocardiography was performed to determine left ventricular morphology and function. Statistical significance was determined by one-way ANOVA, with significance set at p<0.05. RESULTS: Fructose overload induced a metabolic syndrome state, as confirmed by insulin resistance (F: 3.6 +/- 0.2 vs. C: 4.5 +/- 0.2 mg/dl/min), hypertension (mean blood pressure, F: 118 +/- 3 vs. C: 104 +/- 4 mmHg) and obesity (F: 0.31 +/- 0.001 vs. C: 0.29 +/- 0.001 g/mm). Interestingly, fructose overload rats also exhibited diastolic dysfunction. Exercise training performed during the period of high fructose intake eliminated all of these derangements. The improvements in metabolic parameters were correlated with the maintenance of diastolic function. CONCLUSION: The role of exercise training in the prevention of metabolic and hemodynamic parameter alterations is of great importance in decreasing the cardiac morbidity and mortality related to metabolic syndrome.
- Moderate exercise training promotes adaptations in coronary blood flow and adenosine production in normotensive rats(2011) ROQUE, Fernanda R.; SOCI, Ursula Paula Reno; ANGELIS, Katia De; COELHO, Marcele A.; FURSTENAU, Cristina R.; VASSALLO, Dalton V.; IRIGOYEN, Maria Claudia; OLIVEIRA, Edilamar M.OBJECTIVES: Aerobic exercise training prevents cardiovascular risks. Regular exercise promotes functional and structural adaptations that are associated with several cardiovascular benefits. The aim of this study is to investigate the effects of swimming training on coronary blood flow, adenosine production and cardiac capillaries in normotensive rats. METHODS: Wistar rats were randomly divided into two groups: control (C) and trained (T). An exercise protocol was performed for 10 weeks and 60 min/day with a tail overload of 5% bodyweight. Coronary blood flow was quantified with a color microsphere technique, and cardiac capillaries were quantified using light microscopy. Adenine nucleotide hydrolysis was evaluated by enzymatic activity, and protein expression was evaluated by western blot. The results are presented as the means +/- SEMs (p<0.05). RESULTS: Exercise training increased the coronary blood flow and the myocardial capillary-to-fiber ratio. Moreover, the circulating and cardiac extracellular adenine nucleotide hydrolysis was higher in the trained rats than in the sedentary rats due to the increased activity and protein expression of enzymes, such as E-NTPDase and 5'-nucleotidase. CONCLUSIONS: Swimming training increases coronary blood flow, number of cardiac capillaries, and adenine nucleotide hydrolysis. Increased adenosine production may be an important contributor to the enhanced coronary blood flow and angiogenesis that were observed in the exercise-trained rats; collectively, these results suggest improved myocardial perfusion.
- Monosodium glutamate neonatal treatment induces cardiovascular autonomic function changes in rodents(2012) KONRAD, Signora Peres; FARAH, Vera; RODRIGUES, Bruno; WICHI, Rogerio Brandao; MACHADO, Ubiratan Fabres; LOPES, Heno Ferreira; SCHAAN, Beatriz D'Agord; ANGELIS, Katia De; IRIGOYEN, Maria ClaudiaOBJECTIVES: The aim of this study was to evaluate cardiovascular autonomic function in a rodent obesity model induced by monosodium glutamate injections during the first seven days of life. METHOD: The animals were assigned to control (control, n = 10) and monosodium glutamate (monosodium glutamate, n = 13) groups. Thirty-three weeks after birth, arterial and venous catheters were implanted for arterial pressure measurements, drug administration, and blood sampling. Baroreflex sensitivity was evaluated according to the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine infusion, respectively. Sympathetic and vagal effects were determined by administering methylatropine and propranolol. RESULTS: Body weight, Lee index, and epididymal white adipose tissue values were higher in the monosodium glutamate group in comparison to the control group. The monosodium glutamate-treated rats displayed insulin resistance, as shown by a reduced glucose/insulin index (-62.5%), an increased area under the curve of total insulin secretion during glucose overload (39.3%), and basal hyperinsulinemia. The mean arterial pressure values were higher in the monosodium glutamate rats, whereas heart rate variability (>7 times), bradycardic responses (>4 times), and vagal (similar to 38%) and sympathetic effects (similar to 36%) were reduced as compared to the control group. CONCLUSION: Our results suggest that obesity induced by neonatal monosodium glutamate treatment impairs cardiac autonomic function and most likely contributes to increased arterial pressure and insulin resistance.