RESUMEN
Purpose: Dysregulation of glutamatergic neurotransmission (GN) is linked to sympathetic-respiratory overactivity and hypertension. We investigated whether maternal protein restriction is able to alter GN into the nucleus of the solitary tract (NTS) in adult offspring.Methods: Wistar rat dams were fed with control (NP; 17% protein) or low-protein (LP; 8% protein) diet during pregnancy and lactation, and their offspring were evaluated at 70-90d old. Direct measurements of mean arterial pressure (MAP), heart rate (HR), respiratory frequency (RF) and respiratory (RV) and cardiac (CV) variabilities were assessed in consciousness. The evaluation of GN into NTS over cardiovascular system were assessed by microinjections of unilateral glutamate (L-glu 0.5 nmol/100nL) and bilateral kynurenic acid (Kyn 2.5 nmol/50nL). The NP and LP groups were compared using unpaired Student's t-test where p < 0.05 was considered signiï¬cant.Results: The LP exhibited higher MAP at rest (p = 0.03) and after L-glu microinjection (p = 0.04), as well as an increase over HR after Kyn microinjection when compared to the NP (p = 0.049). In the RV, the LP group showed an increase of the component-standard deviation 1 (p = 0.037) at rest. In the CV, the LP presented an increase of the low frequency (LF) component of the pulse interval (PI) (p = 0.034), a decrease of high frequency (HF) of the PI (p = 0.034), beyond an increased LF/HF ratio of the PI (p = 0.027) when compared to the NP. The kynurenic acid microinjection did not produce changes in RV or CV (p > 0.05).Conclusions: Altered GN into the NTS may contribute to augmented blood pressure in protein-restricted offspring.
Asunto(s)
Sistema Cardiovascular , Ácido Glutámico , Animales , Presión Sanguínea , Estado de Conciencia , Dieta con Restricción de Proteínas , Femenino , Ácido Glutámico/metabolismo , Frecuencia Cardíaca/fisiología , Humanos , Microinyecciones , Embarazo , Ratas , Ratas Wistar , Núcleo Solitario/metabolismoRESUMEN
BACKGROUND AND AIMS: Maternal undernutrition induces development of the arterial hypertension. We investigated the effects of a maternal low-protein diet on cardiovascular autonomic control in the offspring. METHODS AND RESULTS: Male Wistar rats were divided into two groups according to the diets of their mothers during gestation and lactation: the control (normal protein, NP, 17% casein; n = 14) and low-protein (LP, 8% casein; n = 14) groups. Direct measurements of arterial pressure (AP) were recorded from wakeful 90-day-old male offspring. The LP offspring presented higher mean AP than did the NP rats (NP: 93 ± 4 vs. LP: 113 ± 2 mmHg; p < 0.05), whereas the heart rate (HR) was similar in the two groups. In the spectral analysis, the LP group showed higher power at low (NP: 1.98 ± 0.25 vs. LP: 3.7 ± 0.3 mmHg²; p < 0.05) and high (NP: 1.28 ± 0.18 vs. LP: 2.13 ± 0.42 mmHg²; p < 0.05) frequencies of systolic arterial pressure (SAP). In the pulse interval, the LP group presented an increase in the LF/HF ratio (NP: 0.32 vs. LP: 0.56; p < 0.05). After propranolol (4 mg/kg, intravenous (iv)), the bradycardia was higher in the LP group (NP: -36 ± 8 vs. LP: -94 ± 12 bpm; p < 0.05), after methylatropine (2 mg/kg, iv), the tachycardia was similar to NP group. After administration of the ganglionic blocker (hexamethonium; 25 mg/kg, iv), the LP animals showed larger delta variation in the AP (NP: -33.7 ± 5 vs. LP: -53.6 ± 4 mmHg; p < 0.05). CONCLUSION: The rats subjected to protein malnutrition presented an increase in the cardiovascular sympathetic tone, which contributed to the elevated AP observed in these animals.
Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Sistema Cardiovascular/fisiopatología , Dieta con Restricción de Proteínas/efectos adversos , Hipertensión/etiología , Lactancia , Fenómenos Fisiologicos Nutricionales Maternos , Antagonistas Adrenérgicos beta/farmacología , Animales , Sistema Nervioso Autónomo/efectos de los fármacos , Bradicardia/inducido químicamente , Sistema Cardiovascular/efectos de los fármacos , Sistema Cardiovascular/inervación , Resistencia a Medicamentos , Femenino , Bloqueadores Ganglionares/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Hipertensión/fisiopatología , Masculino , Parasimpatolíticos/farmacología , Embarazo , Análisis de la Onda del Pulso , Ratas Wistar , Simpaticolíticos/farmacología , Taquicardia/inducido químicamenteRESUMEN
Heart rate variability (HRV) is a relevant physiological variable for the estimation of cardiac autonomic function. Although the gold standard for HRV registration is the electrocardiogram (ECG), several applications (APPs) have been increasingly developed. The evaluation carried out by these devices must be compatible with ECG standards. The aim of this study was to compare the data obtained simultaneously with ECG and APP with chest heart rate transmitters. Fifty-six healthy individuals (28 men and 28 women) were evaluated at rest through a short simultaneous HRV measurement with both devices. Data from both acquisition systems were analyzed separately using their own analysis software and exported and analyzed using a validated software. Signal recordings were compatible between the two acquisition systems (Pearson r=0.99; P<0.0001). Although a high correlation was found for the HRV variables obtained in the time domain (Spearman r=0.99; P<0.0001), the correlation decreased in the frequency domain (Pearson r=0.85; P<0.0001) when two software programs were used. Comparison of the averages of spectral analysis parameters also showed differences when HRV data were analyzed separately in each device for low-frequency (LF) and high-frequency (HF) bands. Although the portability of these mobile devices allows for optimal HRV evaluation, the direct analysis obtained from these devices must be carefully evaluated with respect to frequency domain parameters.
Asunto(s)
Sistema Nervioso Autónomo , Electrocardiografía , Femenino , Corazón , Frecuencia Cardíaca , Humanos , MasculinoRESUMEN
Pulmonary arterial hypertension (PAH), characterized by localized increased arterial blood pressure in the lungs, is a slow developing long-term disease that can be fatal. PAH is characterized by inflammation, vascular tone imbalance, pathological pulmonary vascular remodeling, and right-sided heart failure. Current treatments for PAH are palliative and development of new therapies is necessary. Recent and relevant studies have demonstrated that epigenetic processes may exert key influences on the pathogenesis of PAH and may be promising therapeutic targets in the prevention and/or cure of this condition. The aim of the present mini-review is to summarize the occurrence of epigenetic-based mechanisms in the context of PAH physiopathology, focusing on the roles of DNA methylation, histone post-translational modifications and non-coding RNAs. We also discuss the potential of epigenetic-based therapies for PAH.
Asunto(s)
Metilación de ADN/genética , Epigénesis Genética/genética , Código de Histonas/genética , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/fisiopatología , ARN no Traducido/genética , Regulación hacia Abajo/genética , Humanos , Hipertensión Pulmonar/terapia , Terapia Molecular Dirigida , Arteria Pulmonar/patología , Ubiquitinación/genética , Regulación hacia Arriba/genéticaRESUMEN
The aim of this study was to investigate the reproductive, biochemical, and hematological outcomes of pregnant rats exposed to protein restriction. Wistar rat dams were fed a control normal-protein (NP, 17% protein, n=8) or a low-protein (LP, 8% protein, n=14) diet from the 1st to the 20th day of pregnancy. On the 20th day, the clinical signs of toxicity were evaluated. The pregnant rats were then anesthetized and blood samples were collected for biochemical-hematological analyses, and laparotomy was performed to evaluate reproductive parameters. No sign of toxicity, or differences (P>0.05) in body weight gain and biochemical parameters (urea, creatinine, albumin, globulin, and total protein) between NP and LP pregnant dams were observed. Similarly, hematological data, including red blood cell count, white blood cell count, hemoglobin, hematocrit, red blood cell distribution width (coefficient of variation), mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, % lymphocytes, absolute lymphocyte count, platelet count, and mean platelet volume were similar (P>0.05) at the end of pregnancy. Reproductive parameters (the dam-offspring relationship, ovary mass, placenta mass, number of corpora lutea, implantation index, resorption index, and the pre- and post-implantation loss rates) were also not different (P>0.05) between NP and LP pregnant dams. The present data showed that a protein-restricted diet during pregnancy did not alter reproductive, biochemical, and hematological parameters and seems not to have any toxic effect on pregnant Wistar rats.
Asunto(s)
Adaptación Fisiológica/fisiología , Dieta con Restricción de Proteínas/métodos , Desarrollo Fetal/fisiología , Genitales Femeninos/fisiología , Albúminas/análisis , Animales , Creatinina/sangre , Recuento de Eritrocitos , Femenino , Globulinas/análisis , Hematócrito , Hemoglobinas/análisis , Recuento de Leucocitos , Masculino , Embarazo , Proteínas/análisis , Ratas , Ratas Wistar , Urea/sangre , Aumento de Peso/fisiologíaRESUMEN
Heart rate variability (HRV) is a relevant physiological variable for the estimation of cardiac autonomic function. Although the gold standard for HRV registration is the electrocardiogram (ECG), several applications (APPs) have been increasingly developed. The evaluation carried out by these devices must be compatible with ECG standards. The aim of this study was to compare the data obtained simultaneously with ECG and APP with chest heart rate transmitters. Fifty-six healthy individuals (28 men and 28 women) were evaluated at rest through a short simultaneous HRV measurement with both devices. Data from both acquisition systems were analyzed separately using their own analysis software and exported and analyzed using a validated software. Signal recordings were compatible between the two acquisition systems (Pearson r=0.99; P<0.0001). Although a high correlation was found for the HRV variables obtained in the time domain (Spearman r=0.99; P<0.0001), the correlation decreased in the frequency domain (Pearson r=0.85; P<0.0001) when two software programs were used. Comparison of the averages of spectral analysis parameters also showed differences when HRV data were analyzed separately in each device for low-frequency (LF) and high-frequency (HF) bands. Although the portability of these mobile devices allows for optimal HRV evaluation, the direct analysis obtained from these devices must be carefully evaluated with respect to frequency domain parameters.
RESUMEN
The present study investigated the impact of a western diet during gestation and lactation on the anthropometry, serum biochemical, blood pressure and cardiovascular autonomic control on the offspring. Male Wistar rats were divided into two groups according to their mother's diet received: control group (C: 18% calories of lipids) and westernized group (W: 32% calories of lipids). After weaning both groups received standard diet. On the 60th day of life, blood samples were collected for the analysis of fasting glucose and lipidogram. Cardiovascular parameters were measured on the same period. Autonomic nervous system modulation was evaluated by spectrum analysis of heart rate (HR) and systolic arterial pressure (SAP). The W increased glycemia (123±2 v. 155±2 mg/dl), low-density lipoprotein (15±1 v. 31±2 mg/dl), triglycerides (49±1 v. 85±2 mg/dl), total cholesterol (75±2 v. 86±2 mg/dl), and decreased high-density lipoprotein (50±4 v. 38±3 mg/dl), as well as increased body mass (209±4 v. 229±6 g) than C. Furthermore, the W showed higher SAP (130±4 v. 157±2 mmHg), HR (357±10 v. 428±14 bpm), sympathetic modulation to vessels (2.3±0.56 v. 6±0.84 mmHg2) and LF/HF ratio (0.15±0.01 v. 0.7±0.2) than C. These findings suggest that a western diet during pregnancy and lactation leads to overweight associated with autonomic misbalance and hypertension in adulthood.
Asunto(s)
Dieta Occidental/efectos adversos , Fenómenos Fisiologicos Nutricionales Maternos , Disautonomías Primarias/inducido químicamente , Disautonomías Primarias/patología , Animales , Presión Sanguínea/efectos de los fármacos , Femenino , Masculino , Embarazo , Ratas , Ratas WistarRESUMEN
Pulmonary arterial hypertension (PAH), characterized by localized increased arterial blood pressure in the lungs, is a slow developing long-term disease that can be fatal. PAH is characterized by inflammation, vascular tone imbalance, pathological pulmonary vascular remodeling, and right-sided heart failure. Current treatments for PAH are palliative and development of new therapies is necessary. Recent and relevant studies have demonstrated that epigenetic processes may exert key influences on the pathogenesis of PAH and may be promising therapeutic targets in the prevention and/or cure of this condition. The aim of the present mini-review is to summarize the occurrence of epigenetic-based mechanisms in the context of PAH physiopathology, focusing on the roles of DNA methylation, histone post-translational modifications and non-coding RNAs. We also discuss the potential of epigenetic-based therapies for PAH.