RESUMO
PURPOSE: Metabolic syndrome (MS) increases the risk of type 2 diabetes and cardiovascular disease. High consumption of fructose is a proposed cause of increased MS, manifested through hypertension, obesity, insulin resistance, and dyslipidemia. High NaCl also increases the risk of CD. The purpose of this study is to evaluate the influence of fructose and sodium on autonomic dysfunction and its relation with CD in MS. Fructose overload was started at weaning and continued through adulthood. METHODS: Male Wistar rats (21 days) were divided into four groups: Control (C), fructose consumption (10%, F), NaCl consumption (salt 1% for the 10 last days, S), and fructose and NaCl (FS), and monitored for 8 weeks. Metabolic evaluations consisted of Lee index, glycemia, insulin and glucose tolerance tests, triglycerides, and total cholesterol measurements. Cardiovascular parameters measured were arterial pressure (AP) and cardiac function performed by echocardiography. They also measured the influence of renin angiotensin (RAS) and autonomic nervous systems by drug blockage with losartan, atropine, and atenolol. RESULTS: Energy analysis showed no change between groups. Fructose overload induced a MS state, confirmed by insulin resistance, glucose intolerance, and dyslipidemia. Fasting glucose was increased in F and FS rat groups compared with C and S groups. AP was higher in F, S, and FS groups in comparison with the C group. The hypotensive response after sympathetic blockade was increased in F, S, and FS versus C. The cardiac vagal tonus was reduced in F and FS animal groups. The intrinsic heart rate was decreased in the FS group (372 ± 9 bpm) compared with the C group (410 ± 13 bpm). The morphometric measurements evaluated through left ventricular diameter during diastole and the left ventricular diameter during systole decreased in the FS group (16 and 26%, respectively). Diastolic function was reduced in F and FS. The depressor response induced by losartan was increased in the F group in comparison with other groups. However, there was a uniform increase in plasma ACE activity in all treated groups compared with the C group. CONCLUSIONS: Data suggest that early exposure to high fructose intake produced marked alterations in metabolic and cardiovascular function. When stimulated by NaCl, the fructose-fed subjects showed further impairment in cardiac function.
Assuntos
Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Frutose/efeitos adversos , Cloreto de Sódio na Dieta/efeitos adversos , Animais , Pressão Arterial , Glicemia/metabolismo , Pressão Sanguínea , Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Frutose/administração & dosagem , Intolerância à Glucose/sangue , Intolerância à Glucose/fisiopatologia , Teste de Tolerância a Glucose , Coração/fisiopatologia , Frequência Cardíaca , Insulina/sangue , Resistência à Insulina , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Ratos , Ratos Wistar , Sistema Renina-Angiotensina , Cloreto de Sódio na Dieta/administração & dosagem , Triglicerídeos/sangueRESUMO
AIMS: This study sought to investigate the metabolic, hemodynamic and autonomic responses in adult rats exposed to high-fat diet since post-weaning. MAIN METHODS: Young male Wistar rats were assigned into groups fed with standard normal diet (3% lipids; ND, n=8) or high-fat diet (30% lipids; HD, n=8) during 8weeks. Body composition, food intake, serum triglycerides, total cholesterol, insulin, leptin and adiponectin concentrations were determined. Hemodynamic and autonomic evaluations were performed. Renin angiotensin system and nitric oxide were also studied by pharmacological blockades. KEY FINDINGS: HD group showed no difference in body weight, total cholesterol, food intake in calories and insulin concentration, but visceral fat pads weight, triglycerides and leptin were higher in HD group. Moreover, HD group decreased adiponectin level, increased 12% of mean arterial pressure (MAP) and 6% of heart rate compared with ND group. Spectral analyses showed an increase in cardiovascular sympathetic modulation in HD compared with ND group. Depressor responses after losartan were higher in HD compared with ND group: -9±0.7 vs.-3±1.6mmHg. Pressor responses after l-NAME were higher in HD compared with ND: 45±8 vs. 32±5mmHg. SIGNIFICANCE: High-fat diet consumption during early period of life can increase WAT mass and MAP. These alterations may be mediated by an augment in sympathetic activity associated with higher leptin and lower adiponectin levels. These cardiometabolic damages can lead to the development of hypertension and increase cardiovascular risk in adulthood.
Assuntos
Sistema Cardiovascular/fisiopatologia , Dieta Hiperlipídica , Metabolismo , Desmame , Adiposidade , Animais , Masculino , Ratos , Ratos Wistar , Aumento de PesoRESUMO
The use of colored microspheres to adequately evaluate blood flow changes under different circumstances in the same rat has been validated with a maximum of three different colors due to methodological limitations. The aim of the present study was to validate the use of four different colors measuring four repeated blood flow changes in the same rat to assess the role of vasopressor systems in controlling arterial pressure (AP). Red (150,000), white (200,000), yellow (150,000), and blue (200,000) colored microspheres were infused into the left ventricle of 6 male Wistar rats 1) at rest and 2) after vasopressin (aAVP, 10 microg/kg, iv), 3) renin-angiotensin (losartan, 10 mg/kg, iv), and 4) sympathetic system blockade (hexamethonium, 20 mg/kg, iv) to determine blood flow changes. AP was recorded and processed with a data acquisition system (1-kHz sampling frequency). Blood flow changes were quantified by spectrophotometry absorption peaks for colored microsphere components in the tissues evaluated. Administration of aAVP and losartan slightly reduced the AP (-5.7 +/- 0.5 and -7.8 +/- 1.2 mmHg, respectively), while hexamethonium induced a 52 +/- 3 mmHg fall in AP. The aAVP injection increased blood flow in lungs (78%), liver (117%) and skeletal muscle (>150%), while losartan administration enhanced blood flow in heart (126%), lungs (100%), kidneys (80%), and gastrocnemius (75%) and soleus (94%) muscles. Hexamethonium administration reduced only kidney blood flow (50%). In conclusion, four types of colored microspheres can be used to perform four repeated blood flow measurements in the same rat detecting small alterations such as changes in tissues with low blood flow.
Assuntos
Anti-Hipertensivos/farmacologia , Arginina Vasopressina/análogos & derivados , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Microesferas , Animais , Arginina Vasopressina/farmacologia , Débito Cardíaco/efeitos dos fármacos , Cor , Hexametônio/farmacologia , Losartan/farmacologia , Masculino , Ratos , Ratos Wistar , Fluxo Sanguíneo Regional/efeitos dos fármacos , Espectrofotometria AtômicaRESUMO
The aim of the present study was to evaluate the sensitivity of the cardiopulmonary receptors in experimental diabetes induced by streptozotocin by the use of 2 different methods: (1) administration of increasing doses of serotonin to analyze peak changes of arterial pressure and heart rate for each given dose in conscious intact normal and diabetic rats; (2) expanding blood volume with the use of dextran (6%) to produce similar increases in left ventricular end-diastolic pressure to quantify the arterial pressure, heart rate, and renal sympathetic nerve activity in sinoaortic, denervated, anesthetized normal and diabetic rats. Blood samples were collected to measure blood glucose. Diabetic rats showed hyperglycemia (22+/-0. 7 versus 7+/-0.2 mmol/L), reduced body weight (226+/-12 versus 260+/-4 g) and heart rate (294+/-14 versus 350+/-10 bpm), and similar arterial pressure (104+/-4 versus 113+/-4 mm Hg) when compared with control rats. Serotonin induced significant bradycardia and hypotension, which were similar and proportional to the dose injected in both groups. Mean arterial pressure and heart rate decreases in response to volume overload were significantly lower in diabetic than in control rats. The reflex reduction of the renal sympathetic nerve activity as expressed by percentage changes in nerve activity in response to increasing left end-diastolic pressure was abolished in diabetic animals (1.9+/-0.8% versus -14+/-4%/mm Hg in controls). These results showed an impairment of cardiopulmonary reflex control of circulation in diabetes during acute volume expansion. The normal responses to serotonin administration indicated that the cardiopulmonary reflex is still preserved in diabetic rats.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Reflexo , Sistema Nervoso Simpático/fisiopatologia , Animais , Volume Sanguíneo , Dextranos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Coração/inervação , Coração/fisiologia , Pulmão/inervação , Pulmão/fisiologia , Masculino , Substitutos do Plasma/farmacologia , Ratos , Ratos Wistar , Serotonina/farmacologiaRESUMO
The present investigation was undertaken to evaluate the vagal function of trained (T) and sedentary (S) rats by use of different approaches in the same animal. After 13 wk of exercise training (treadmill for 1 h 5 times/wk at 26.8 m/min and 15% grade), T rats had a resting heart rate (HR) slightly but significantly lower than S rats (299 +/- 3 vs. 308 +/- 3 beats/min). T rats had marked reduction of the intrinsic HR (329 +/- 4 vs. 369 +/- 5 beats/min) after blockade by methylatropine and propranolol. They also exhibited depressed vagal and sympathetic tonus. Baroreflex bradycardia (phenylephrine injections) was reduced, bradycardic responses produced by electrical stimulation of the vagus were depressed, and responses to methacholine injection were decreased in T rats. Therefore several evidences of vagal function impairment were observed in T rats. The resting bradycardia after exercise training is more likely to be dependent on alterations of the pacemaker cells, inasmuch as the intrinsic HR was markedly reduced.
Assuntos
Esforço Físico/fisiologia , Nervo Vago/fisiopatologia , Animais , Pressão Sanguínea/fisiologia , Bradicardia/etiologia , Bradicardia/fisiopatologia , Estimulação Elétrica , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Masculino , Cloreto de Metacolina/farmacologia , Condicionamento Físico Animal , Pressorreceptores/fisiologia , Ratos , Ratos Endogâmicos , Reflexo/fisiologiaRESUMO
1. The effects of sodium pentobarbital and alpha-chloralose anesthesia on the baroreflex control of circulation were studied in groups of 7 to 11 rats. The tests were performed in conscious undisturbed rats and repeated after anesthesia. 2. Pentobarbital (15 min) depressed the initial peak of the pressor response produced by carotid occlusion by 68% (15 +/- 1 vs 47 +/- 3 mmHg) and the maintained response by 52% (13 +/- 1 vs 27 +/- 4). Depression by chloralose was 48% (26 +/- 5 vs 50 +/- 3) and 21% (19 +/- 2 vs 24 +/- 3), respectively. The inhibition progressively declined at 30, 60, 90 and 120 min after pentobarbital but was unchanged up to 120 min after chloralose. 3. The baroreflex sensitivity index for bradycardic responses (phenylephrine injection) diminished by 50% after pentobarbital (-1.1 +/- 0.3 vs -2.2 +/- 0.3 beats/min per mmHg) and remained unaltered after chloralose. 4. The baroreflex sensitivity index for tachycardic responses (nitroprusside injection) was depressed by 61% after pentobarbital (-1.5 +/- 0.5 vs -3.8 +/- 0.5 beats/min per mmHg) and 35% after chloralose (-2.5 +/- 0.2 vs -3.9 +/- 0.5). 5. In general the depression of reflex control of circulation was more severe after pentobarbital than after chloralose anesthesia, while the resting control arterial pressure was not affected by either. The inhibition of the baroreflex tachycardic responses was more intense than that of the bradycardic responses and represented a better index of the depression exerted on the pressure responses to carotid occlusion.
Assuntos
Cloralose/farmacologia , Frequência Cardíaca , Pentobarbital/farmacologia , Pressorreceptores/efeitos dos fármacos , Animais , Bradicardia/induzido quimicamente , Cloralose/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Masculino , Nitroprussiato , Pentobarbital/administração & dosagem , Fenilefrina , Pressorreceptores/fisiologia , Ratos , Ratos Endogâmicos , Taquicardia/induzido quimicamenteRESUMO
Baroreflex sensitivity was studied in the same group of conscious rats using vasoactive drugs (phenylephrine and sodium nitroprusside) administered by three different approaches: 1) bolus injection, 2) steady-state (blood pressure (BP) changes produced in steps), 3) ramp infusion (30 s, brief infusion). The heart rate (HR) responses were evaluated by the mean index (mean ratio of all HR changes and mean arterial pressure (MAP) changes), by linear regression and by the logistic method (maximum gain of the sigmoid curve by a logistic function). The experiments were performed on three consecutive days. Basal MAP and resting HR were similar on all days of the study. Bradycardic responses evaluated by the mean index (-1.5 +/- 0.2, -2.1 +/- 0.2 and -1.6 +/- 0.2 bpm/mmHg) and linear regression (-1.8 +/- 0.3, -1.4 +/- 0.3 and -1.7 +/- 0.2 bpm/mmHg) were similar for all three approaches used to change blood pressure. The tachycardic responses to decreases of MAP were similar when evaluated by linear regression (-3.9 +/- 0.8, -2.1 +/- 0.7 and -3.8 +/- 0.4 bpm/mmHg). However, the tachycardic mean index (-3.1 +/- 0.4, -6.6 +/- 1 and -3.6 +/- 0.5 bpm/mmHg) was higher when assessed by the steady-state method. The average gain evaluated by logistic function (-3.5 +/- 0.6, -7.6 +/- 1.3 and -3.8 +/- 0.4 bpm/mmHg) was similar to the reflex tachycardic values, but different from the bradycardic values. Since different ways to change BP may alter the afferent baroreceptor function, the MAP changes obtained during short periods of time (up to 30 s: bolus and ramp infusion) are more appropriate to prevent the acute resetting. Assessment of the baroreflex sensitivity by mean index and linear regression permits a separate analysis of gain for reflex bradycardia and reflex tachycardia. Although two values of baroreflex sensitivity cannot be evaluated by a single symmetric logistic function, this method has the advantage of better comparing the baroreflex sensitivity of animals with different basal blood pressures.
Assuntos
Barorreflexo , Determinação da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Estado de Consciência , Frequência Cardíaca/fisiologia , Pressorreceptores/fisiologia , Análise de Variância , Animais , Pressão Sanguínea/efeitos dos fármacos , Bradicardia , Frequência Cardíaca/efeitos dos fármacos , Modelos Lineares , Masculino , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Ratos , Ratos Wistar , TaquicardiaRESUMO
To assess the role of angiotensin II in the sensitivity of the baroreflex control of heart rate (HR) in normotensive rats (N = 6) and chronically hypertensive rats (1K1C, 2 months, N = 7), reflex changes of HR were evaluated before and after (15 min) the administration of a selective angiotensin II receptor antagonist (losartan, 10 mg/kg, iv). Baseline values of mean arterial pressure (MAP) were higher in hypertensive rats (195 +/- 6 mmHg) than in normotensive rats (110 +/- 2 mmHg). Losartan administration promoted a decrease in MAP only in hypertensive rats (16%), with no changes in HR. During the control period, the sensitivity of the bradycardic and tachycardic responses to acute MAP changes were depressed in hypertensive rats (approximately 70% and approximately 65%, respectively) and remained unchanged after losartan administration. Plasma renin activity was similar in the two groups. The present study demonstrates that acute blockade of AT1 receptors with losartan lowers the MAP in chronic renal hypertensive rats without reversal of baroreflex hyposensitivity, suggesting that the impairment of baroreflex control of HR is not dependent on an increased angiotensin II level.
Assuntos
Antagonistas de Receptores de Angiotensina , Anti-Hipertensivos/uso terapêutico , Barorreflexo/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipertensão Renal/tratamento farmacológico , Losartan/uso terapêutico , Angiotensina II/fisiologia , Animais , Anti-Hipertensivos/farmacologia , Bradicardia/tratamento farmacológico , Doença Crônica , Hipertensão Renal/fisiopatologia , Losartan/farmacologia , Masculino , Ratos , Receptor Tipo 1 de Angiotensina , Receptor Tipo 2 de Angiotensina , Taquicardia/tratamento farmacológicoRESUMO
Ethylene-bis-dithiocarbamate (EBDC) residues were determined as carbon disulfide (CS2) by an improved headspace gas-liquid chromatographic (GLC) procedure. Among 837 samples of 30 agricultural commodities tested, 43% contained residues above the detection limit for the method: 100% of broccoli samples; 80% of cabbage, kiwifruit, and grape samples; and 71% of cucumber samples. Most of the residues in kiwifruit were on or near the skin. Elimination of false-positive detections by the improved method was confirmed with kiwifruit in 2 independent procedures. Whole fruits were washed with 5% EDTA to remove surface residues of EBDC. Analysis of washes for CS2 by the headspace procedure after treatment with acidic stannous chloride and for ethylene thiourea by LC after prolonged treatment at 60 degrees C qualitatively identified the EDTA-soluble residues as EBDC. Although the improved method does not produce false-positive results, peak area responses of CS2 and the internal standard, thiophene, are influenced by chemical composition of the matrix. With matrixes high in sugar or lipids, the apparent CS2 content may be overestimated by 4-fold. Accurate determination of EBDC residues in these sample types requires appropriate adjustments to matrixes.
Assuntos
Etilenobis (ditiocarbamatos)/análise , Inseticidas/análise , Resíduos de Praguicidas/análise , Austrália , Dissulfeto de Carbono/análise , Dissulfeto de Carbono/química , Cromatografia Gasosa , Etilenobis (ditiocarbamatos)/química , Etilenotioureia/análise , Etilenotioureia/química , Análise de Alimentos/normas , Contaminação de Alimentos , Frutas/química , Inseticidas/química , Resíduos de Praguicidas/química , Padrões de Referência , Espectrofotometria Ultravioleta , Verduras/químicaRESUMO
We compared the effects produced by acute and chronic administration of captopril in sinoaortic denervated rats. In conscious undisturbed rats acute administration of captopril (10 mg/kg intravenously) produced acute transient reductions in mean arterial pressure of 16 and 26%, 6 h (mean arterial pressure 148 +/- 4 mmHg) and 24 h (133 +/- 3 mmHg) after the sinoaortic denervation, respectively. Chronic captopril treatment (30 mg/day orally) produced a permanent attenuation of the hypertension induced by sino-aortic denervation, as shown by a beat-to-beat analysis of arterial pressure for 80 min. The attenuation was 11% (131 +/- 7 versus 148 +/- 4 mmHg) and 24% (103 +/- 9 versus 133 +/- 3 mmHg) in rats studied 6 and 24 h after the sinoaortic denervation, respectively. Chronic captopril administration produced no alteration in the tachycardia, nor in the heart rate variability of the sinoaortic denervated rats; the latter was lower than that of normotensive rats. These data show that while acute administration of captopril in sinoaortic denervated rats produced a rapid hypotensive response, chronic administration produced a long-lasting attenuation of hypertension, presumably by interference with sympathetic cardiovascular control.
Assuntos
Captopril/uso terapêutico , Hipertensão/tratamento farmacológico , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Denervação , Avaliação Pré-Clínica de Medicamentos , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Hipertensão/etiologia , Hipertensão/fisiopatologia , Masculino , Ratos , Ratos Endogâmicos , Seio Aórtico/inervação , Fatores de TempoRESUMO
We determined the sympathetic and parasympathetic control of heart rate (HR) and the sensitivity of the cardiopulmonary receptors after selective carotid and aortic denervation. We also investigated the participation of the autonomic nervous system in the Bezold-Jarish reflex after selective removal of aortic and carotid baroreceptors. Male Wistar rats (220-270 g) were divided into three groups: control (CG, N = 8), aortic denervation (AG, N = 5) and carotid denervation (CAG, N = 9). AG animals presented increased arterial pressure (12%) and HR (11%) compared with CG, while CAG animals presented a reduction in arterial pressure (16%) and unchanged HR compared with CG. The sequential blockade of autonomic effects by atropine and propranolol indicated a reduction in vagal function in CAG (a 50 and 62% reduction in vagal effect and tonus, respectively) while AG showed an increase of more than 100% in sympathetic control of HR. The Bezold-Jarish reflex was evaluated using serotonin, which induced increased bradycardia and hypotension in AG and CAG, suggesting that the sensitivity of the cardiopulmonary reflex is augmented after selective denervation. Atropine administration abolished the bradycardic responses induced by serotonin in all groups; however, the hypotensive response was still increased in AG. Although the responses after atropine were lower than the responses before the drug, indicating a reduction in vagal outflow after selective denervation, our data suggest that both denervation procedures are associated with an increase in sympathetic modulation of the vessels, indicating that the sensitivity of the cardiopulmonary receptors was modulated by baroreceptor fibers.
Assuntos
Aorta Torácica/inervação , Seio Carotídeo/inervação , Pressorreceptores/fisiologia , Reflexo/fisiologia , Animais , Sistema Nervoso Autônomo/fisiologia , Pressão Sanguínea , Masculino , Ratos , Ratos WistarRESUMO
We determined the sympathetic and parasympathetic control of heart rate (HR) and the sensitivity of the cardiopulmonary receptors after selective carotid and aortic denervation. We also investigated the participation of the autonomic nervous system in the Bezold-Jarish reflex after selective removal of aortic and carotid baroreceptors. Male Wistar rats (220-270 g) were divided into three groups: control (CG, N = 8), aortic denervation (AG, N = 5) and carotid denervation (CAG, N = 9). AG animals presented increased arterial pressure (12 percent) and HR (11 percent) compared with CG, while CAG animals presented a reduction in arterial pressure (16 percent) and unchanged HR compared with CG. The sequential blockade of autonomic effects by atropine and propranolol indicated a reduction in vagal function in CAG (a 50 and 62 percent reduction in vagal effect and tonus, respectively) while AG showed an increase of more than 100 percent in sympathetic control of HR. The Bezold-Jarish reflex was evaluated using serotonin, which induced increased bradycardia and hypotension in AG and CAG, suggesting that the sensitivity of the cardiopulmonary reflex is augmented after selective denervation. Atropine administration abolished the bradycardic responses induced by serotonin in all groups; however, the hypotensive response was still increased in AG. Although the responses after atropine were lower than the responses before the drug, indicating a reduction in vagal outflow after selective denervation, our data suggest that both denervation procedures are associated with an increase in sympathetic modulation of the vessels, indicating that the sensitivity of the cardiopulmonary receptors was modulated by baroreceptor fibers.
Assuntos
Animais , Masculino , Ratos , Aorta Torácica/inervação , Seio Carotídeo/inervação , Pressorreceptores/fisiologia , Reflexo/fisiologia , Sistema Nervoso Autônomo/fisiologia , Pressão Sanguínea , Ratos WistarRESUMO
The baroreflex control of heart rate (HR) was evaluated in conscious chronic renal hypertensive rats (RHR; 1K-1C, 2 mo) under control conditions and after reversal of hypertension by unclipping the renal artery or sodium nitroprusside infusion. Unclipping and nitroprusside infusion were both followed by significant decreases in the mean arterial pressure (unclipping: from 199 +/- 4 to 153 +/- 8 mmHg; nitroprusside infusion: from 197 +/- 9 to 166 +/- 6 mmHg) as well as slight and significant increases, respectively, in the baroreflex bradycardic response index (unclipping: from 0.2 +/- 0.04 to 0.6 +/- 0.1 beats x min(-1) x mmHg(-1); nitroprusside infusion: from 0.1 +/- 0.04 to 0.5 +/- 0.1 beats x min(-1) x mmHg(-1)). However, this index was still depressed compared with that for normotensive control rats (2.1 +/- 0.2 beats x min(-1) x mmHg(-1)). The index for the baroreflex tachycardic response was also depressed under control conditions and remained unchanged after hypertension reversal. RHR possessed markedly attenuated vagal tone as demonstrated by pharmacological blockade of parasympathetic and sympathetic control of HR with methylatropine and propranolol, respectively. A reduced bradycardic response was also observed in anesthetized RHR during electrical stimulation of the vagus nerve or methacholine chloride injection, indicating impairment of efferent vagal influence over the HR. Together, these data indicate that 2 h after hypertension reversal in RHR, the previously described normalization of baroreceptor gain occurs independent of the minimal or lack of recovery of baroreflex control over HR.
Assuntos
Barorreflexo , Hipertensão Renovascular/fisiopatologia , Animais , Barorreflexo/efeitos dos fármacos , Bradicardia/induzido quimicamente , Relação Dose-Resposta a Droga , Masculino , Cloreto de Metacolina/administração & dosagem , Agonistas Muscarínicos/administração & dosagem , Nitroprussiato/farmacologia , Ratos , Recuperação de Função Fisiológica , Valores de Referência , Renina/sangue , Sistema Nervoso Simpático/fisiopatologia , Fatores de Tempo , Nervo Vago/fisiopatologiaRESUMO
The use of colored microspheres to adequately evaluate blood flow changes under different circumstances in the same rat has been validated with a maximum of three different colors due to methodological limitations. The aim of the present study was to validate the use of four different colors measuring four repeated blood flow changes in the same rat to assess the role of vasopressor systems in controlling arterial pressure (AP). Red (150,000), white (200,000), yellow (150,000), and blue (200,000) colored microspheres were infused into the left ventricle of 6 male Wistar rats 1) at rest and 2) after vasopressin (aAVP, 10 æg/kg, iv), 3) renin-angiotensin (losartan, 10 mg/kg, iv), and 4) sympathetic system blockade (hexamethonium, 20 mg/kg, iv) to determine blood flow changes. AP was recorded and processed with a data acquisition system (1-kHz sampling frequency). Blood flow changes were quantified by spectrophotometry absorption peaks for colored microsphere components in the tissues evaluated. Administration of aAVP and losartan slightly reduced the AP (-5.7 ± 0.5 and -7.8 ± 1.2 mmHg, respectively), while hexamethonium induced a 52 ± 3 mmHg fall in AP. The aAVP injection increased blood flow in lungs (78 percent), liver (117 percent) and skeletal muscle (>150 percent), while losartan administration enhanced blood flow in heart (126 percent), lungs (100 percent), kidneys (80 percent), and gastrocnemius (75 percent) and soleus (94 percent) muscles. Hexamethonium administration reduced only kidney blood flow (50 percent). In conclusion, four types of colored microspheres can be used to perform four repeated blood flow measurements in the same rat detecting small alterations such as changes in tissues with low blood flow.
Assuntos
Animais , Masculino , Ratos , Anti-Hipertensivos/farmacologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Microesferas , Arginina Vasopressina/farmacologia , Cor , Débito Cardíaco/efeitos dos fármacos , Hexametônio/farmacologia , Losartan/farmacologia , Ratos Wistar , Fluxo Sanguíneo Regional/efeitos dos fármacos , Espectrofotometria AtômicaRESUMO
Baroreflex sensitivity was studied in the same group of conscious rats using vasoactive drugs (phenylephrine and sodium nitroprusside) administered by three different approaches: 1) bolus injection, 2) steady-state (blood pressure (BP) changes produced in steps), 3) ramp infusion (30 s, brief infusion). The heart rate (HR) responses were evaluated by the mean index (mean ratio of all HR changes and mean arterial pressure (MAP) changes), by linear regression and by the logistic method (maximum gain of the sigmoid curve by a logistic function). The experiments were performed on three consecutive days. Basal MAP and resting HR were similar on all days of the study. Bradycardic responses evaluated by the mean index (-1.5 ñ 0.2, -2.1 ñ 0.2 and -1.6 ñ 0.2 bpm/mmHg) and linear regression (-1.8 ñ 0.3, -1.4 ñ 0.3 and -1.7 ñ 0.2 bpm/mmHg) were similar for all three approaches used to change blood pressure. The tachycardic responses to decreases of MAP were similar when evaluated by linear regression (-3.9 ñ 0.8, -2.1 ñ 0.7 and -3.8 ñ 0.4 bpm/mmHg). However, the tachycardic mean index (-3.1 ñ 0.4, -6.6 ñ 1 and -3.6 5 0.5 bpm/mmHg) was higher when assessed by the steady-state method. The average gain evaluated by logistic function (-3.5 ñ 0.6, -7.6 ñ 1.3 and -3.8 ñ 0.4 bpm/mmHg) was similar to the reflex tachycardic values, but different from the bradycardic values. Since different ways to change BP may alter the afferent baroreceptor function, the MAP changes obtained during short periods of time (up to 30 s: bolus and ramp infusion) are more appropriate to prevent the acute resetting. Assessment of the baroreflex sensitivity by mean index and linear regression permits a separate analysis of gain for reflex bradycardia and reflex tachycardia. Although two values of baroreflex sensitivity cannot be evaluated by a single symmetric logistic function, this method has the advantage of better comparing the baroreflex sensitivity of animals with different basal blood pressures
Assuntos
Animais , Masculino , Ratos , Barorreflexo , Determinação da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Estado de Consciência , Frequência Cardíaca/fisiologia , Pressorreceptores/fisiologia , Análise de Variância , Pressão Sanguínea/efeitos dos fármacos , Bradicardia , Frequência Cardíaca/efeitos dos fármacos , Modelos Lineares , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Ratos Wistar , TaquicardiaRESUMO
To assess the role of angiotensin II in the sensitivity of the baroreflex control of heart rate (HR) in normotensive rats (N = 6) and chronically hypertensive rats (1K1C, 2 months, N = 7), reflex changes of HR were evaluated before and after (15 min) the administration of a selective angiotensin II receptor antagonist (losartan, 10 mg/kg, iv). Baseline values of mean arterial pressure (MAP) were higher in hypertensive rats (195 ± 6 mmHg) than in normotensive rats (110 ± 2 mmHg). Losartan administration promoted a decrease in MAP only in hypertensive rats (16 percent), with no changes in HR. During the control period, the sensitivity of the bradycardic and tachycardic responses to acute MAP changes were depressed in hypertensive rats (~70 percent and ~65 percent, respectively) and remained unchanged after losartan administration. Plasma renin activity was similar in the two groups. The present study demonstrates that acute blockade of AT1 receptors with losartan lowers the MAP in chronic renal hypertensive rats without reversal of baroreflex hyposensitivity, suggesting that the impairment of baroreflex control of HR is not dependent on an increased angiotensin II level
Assuntos
Masculino , Animais , Ratos , Angiotensina II/fisiologia , Anti-Hipertensivos/uso terapêutico , Barorreflexo/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipertensão Renal/tratamento farmacológico , Losartan/uso terapêutico , Anti-Hipertensivos/farmacologia , Bradicardia/tratamento farmacológico , Doença Crônica , Frequência Cardíaca/efeitos dos fármacos , Losartan/farmacologia , Receptores de Angiotensina/antagonistas & inibidores , Receptores de Angiotensina/metabolismo , Taquicardia/tratamento farmacológicoRESUMO
1. The effects of sodium pentabarbital and alfa-chloralose anesthesia on the barreflex control of ciruclation were studied in groups of 7 to 11 rats. The tests were performed in conscious undisturbed rats and repeated after anesthesia. 2. Pentobarbital (15 min) depressed the initial peak of the pressor response produced by carotid occlusion by 68% (15 ñ 1 vs 47 ñ 3 mmHg) and the mainteined rsponse by 52% (13 ñ 1 vs 27 ñ 4). Depression by chloralose was 48% (26 ñ 5 vs 50 ñ 3) and (19 ñ 2 vs 24 ñ 3), respectively. The inhibition progressively declined at 30, 60.90 and 120 min after pentobarbital but was unchanged up to 120 min after chloralose. 3. The baroreflex sensitivity index for bradycardic responses (phenylephrine injection) diminished by 50% after pentobarbital (-1.1 ñ 0.3 vs -2.2 ñ 0.3 beats/min per mmHg) and remained unaltered after chloralose. 4. The baroreflex sensitivity index for tachycardic responses (nitroprusside injection) was depressed by 61% after pentobarbital (-1.5 ñ 0.5 vs -3.8 - 0.5 beats/min per mmHg) and 35% after chloralose (-2.5 ñ 0.2 vs -3.9 ñ 0,5). 5. In general the depression of reflex control of ciruclation was more severe after pentobarbital than after chloralose anesthesia, while the resting control arterial pressurte was not affected by either. The inhibition of the baroreflex tachycardic responses was more intense than that of the bradycardic responses and represented a betther index of the depression exerted on the pressure responses to carotid occlusion