RESUMO
1. High-sodium intake may increase blood pressure and diabetes is a salt-sensitive condition. In the present study, we evaluated cardiovascular changes and their neurohumoral mechanisms in streptozotocin (STZ)-diabetic rats that underwent chronic salt loading. 2. We studied male Wistar rats (150-280 g) 14 days after the injection of either STZ (50 mg/kg, i.v.; D; n = 18) or citrate buffer (C; n = 16). After the induction of diabetes, animals were maintained for 14 days with free access to standard rat chow and tap water (C and D groups) or 1% NaCl solution (C-S and D-S groups). We conducted two experiments. Experiment 1 consisted of basal arterial pressure (AP) measurement (30 min) followed by the evaluation of AP responsiveness to phenylephrine and sodium nitroprusside. One day later, with the rats anaesthetized, a blood sample was collected to test for glycaemia, plasma angiotensin-converting enzyme (ACE) activity and renin. Kidneys were removed for the determination of tissue ACE activity. Experiment 2 comprised 24 h urine collection followed by 3 days of cardiovascular records, which consisted of a 30 min basal AP measurement, followed by injection of blockers of the vasopressin system, the renin-angiotensin system (RAS) and the sympathetic system. Basal haemodynamic data, baroreflex evaluation and AP responses to blockade of the vasopressin system with vasopressin V(1) receptor antagonist (aAVP; 10 mg/kg, i.v.), the RAS by losartan (10 mg/kg, i.v.) and the sympathetic system by hexamethonium (20 mg/kg, i.v.) were determined. 3. Glycaemia was similar between C and C-S (P = 0.612) and between D and D-S (P = 0.552), but higher in diabetic compared with non-diabetic rats (P < 0.0001). The D-S rats had an increment of 24% in mean AP compared with D (120 +/- 4 vs 97 +/- 2 mmHg, respectively; P = 0.0001), which was not seen in C-S compared with C rats. A positive association was noted between urinary sodium and mean AP (r = 0.37; P = 0.04). Plasma renin was undetectable in D-S rats. The response to acute drug blockade of vasopressin and the RAS was similar among groups, but hexamethonium elicited a more pronounced decrease in AP in D-S compared with D rats (P = 0.001). 4. The main neurohumoral mechanisms of salt-induced cardiovascular changes in STZ-diabetes are increased sodium and vascular sensitivity to adrenergic stimuli, which act in combination to produce a final result of higher AP levels, a finding not observed in control rats. Baroreflex derangements induced by diabetes were not affected by salt overload.
Assuntos
Barorreflexo , Pressão Sanguínea , Diabetes Mellitus Experimental/fisiopatologia , Frequência Cardíaca , Hipertensão/fisiopatologia , Sistema Renina-Angiotensina , Sistema Nervoso Simpático/fisiopatologia , Vasopressinas/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/farmacologia , Barorreflexo/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/urina , Bloqueadores Ganglionares/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hematócrito , Hexametônio/farmacologia , Antagonistas de Hormônios/farmacologia , Hipertensão/sangue , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Hipertensão/urina , Rim/enzimologia , Rim/patologia , Losartan/farmacologia , Masculino , Nitroprussiato/farmacologia , Tamanho do Órgão , Peptidil Dipeptidase A/sangue , Peptidil Dipeptidase A/metabolismo , Fenilefrina/farmacologia , Ratos , Ratos Wistar , Renina/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , Cloreto de Sódio na Dieta , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia , Vasopressinas/antagonistas & inibidoresRESUMO
Streptozotocin (STZ)-induced diabetes in rats is characterized by cardiovascular dysfunction beginning 5 days after STZ injection, which may reflect functional or structural autonomic nervous system damage. We investigated cardiovascular and autonomic function, in rats weighing 166 ± 4 g, 5-7, 14, 30, 45, and 90 days after STZ injection (N = 24, 33, 27, 14, and 13, respectively). Arterial pressure (AP), mean AP (MAP) variability (standard deviation of the mean of MAP, SDMMAP), heart rate (HR), HR variability (standard deviation of the normal pulse intervals, SDNN), and root mean square of successive difference of pulse intervals (RMSSD) were measured. STZ induced increased glycemia in diabetic rats vs control rats. Diabetes reduced resting HR from 363 ± 12 to 332 ± 5 bpm (P < 0.05) 5 to 7 days after STZ and reduced MAP from 121 ± 2 to 104 ± 5 mmHg (P = 0.007) 14 days after STZ. HR and MAP variability were lower in diabetic vs control rats 30-45 days after STZ injection (RMSSD decreased from 5.6 ± 0.9 to 3.4 ± 0.4 ms, P = 0.04 and SDMMAP from 6.6 ± 0.6 to 4.2 ± 0.6 mmHg, P = 0.005). Glycemia was negatively correlated with resting AP and HR (r = -0.41 and -0.40, P < 0.001) and with SDNN and SDMMAP indices (r = -0.34 and -0.49, P < 0.01). Even though STZ-diabetic rats presented bradycardia and hypotension early in the course of diabetes, their autonomic function was reduced only 30-45 days after STZ injection and these changes were negatively correlated with plasma glucose, suggesting a metabolic origin.
Assuntos
Animais , Masculino , Ratos , Sistema Nervoso Autônomo/fisiopatologia , Bradicardia/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Hiperglicemia/fisiopatologia , Glicemia , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Ratos Wistar , Estreptozocina , Fatores de TempoRESUMO
Streptozotocin (STZ)-induced diabetes in rats is characterized by cardiovascular dysfunction beginning 5 days after STZ injection, which may reflect functional or structural autonomic nervous system damage. We investigated cardiovascular and autonomic function, in rats weighing 166 +/- 4 g, 5-7, 14, 30, 45, and 90 days after STZ injection (N = 24, 33, 27, 14, and 13, respectively). Arterial pressure (AP), mean AP (MAP) variability (standard deviation of the mean of MAP, SDMMAP), heart rate (HR), HR variability (standard deviation of the normal pulse intervals, SDNN), and root mean square of successive difference of pulse intervals (RMSSD) were measured. STZ induced increased glycemia in diabetic rats vs control rats. Diabetes reduced resting HR from 363 +/- 12 to 332 +/- 5 bpm (P < 0.05) 5 to 7 days after STZ and reduced MAP from 121 +/- 2 to 104 +/- 5 mmHg (P = 0.007) 14 days after STZ. HR and MAP variability were lower in diabetic vs control rats 30-45 days after STZ injection (RMSSD decreased from 5.6 +/- 0.9 to 3.4 +/- 0.4 ms, P = 0.04 and SDMMAP from 6.6 +/- 0.6 to 4.2 +/- 0.6 mmHg, P = 0.005). Glycemia was negatively correlated with resting AP and HR (r = -0.41 and -0.40, P < 0.001) and with SDNN and SDMMAP indices (r = -0.34 and -0.49, P < 0.01). Even though STZ-diabetic rats presented bradycardia and hypotension early in the course of diabetes, their autonomic function was reduced only 30-45 days after STZ injection and these changes were negatively correlated with plasma glucose, suggesting a metabolic origin.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Bradicardia/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Hiperglicemia/fisiopatologia , Animais , Glicemia , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Estreptozocina , Fatores de TempoRESUMO
Several studies have reported impairment in cardiovascular function and control in diabetes. The studies cited in this review were carried out from a few days up to 3 months after streptozotocin administration and were concerned with the control of the circulation. We observed that early changes (5 days) in blood pressure control by different peripheral receptors were maintained for several months. Moreover, the impairment of reflex responses observed after baroreceptor and chemoreceptor stimulation was probably related to changes in the efferent limb of the reflex arc (sympathetic and parasympathetic), but changes also in the central nervous system could not be excluded. Changes in renal sympathetic nerve activity during volume expansion were blunted in streptozotocin-treated rats, indicating an adaptive natriuretic and diuretic response in the diabetic state. The improvement of diabetic cardiovascular dysfunction induced by exercise training seems to be related to changes in the autonomic nervous system. Complementary studies about the complex interaction between circulation control systems are clearly needed to adequately address the management of pathophysiological changes associated with diabetes.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Sistema Cardiovascular/inervação , Diabetes Mellitus Experimental/fisiopatologia , Frequência Cardíaca/fisiologia , Animais , Barorreflexo/fisiologia , Pressão Sanguínea , Sistema Cardiovascular/fisiopatologia , Células Quimiorreceptoras/fisiologia , Esforço Físico/fisiologia , Ratos , EstreptozocinaRESUMO
Several studies have reported impairment in cardiovascular function and control in diabetes. The studies cited in this review were carried out from a few days up to 3 months after streptozotocin administration and were concerned with the control of the circulation. We observed that early changes (5 days) in blood pressure control by different peripheral receptors were maintained for several months. Moreover, the impairment of reflex responses observed after baroreceptor and chemoreceptor stimulation was probably related to changes in the efferent limb of the reflex arc (sympathetic and parasympathetic), but changes also in the central nervous system could not be excluded. Changes in renal sympathetic nerve activity during volume expansion were blunted in streptozotocin-treated rats, indicating an adaptive natriuretic and diuretic response in the diabetic state. The improvement of diabetic cardiovascular dysfunction induced by exercise training seems to be related to changes in the autonomic nervous system. Complementary studies about the complex interaction between circulation control systems are clearly needed to adequately address the management of pathophysiological changes associated with diabetes
Assuntos
Animais , Ratos , Sistema Nervoso Autônomo , Sistema Cardiovascular , Diabetes Mellitus Experimental , Esforço Físico , Barorreflexo , Pressão Sanguínea , Sistema Cardiovascular , Células Quimiorreceptoras , Frequência Cardíaca , EstreptozocinaRESUMO
Autonomic neuropathy is a frequent complication of diabetes associated with higher morbidity and mortality in symptomatic patients, possibly because it affects autonomic regulation of the sinus node, reducing heart rate (HR) variability which predisposes to fatal arrhythmias. We evaluated the time course of arterial pressure and HR and indirectly of autonomic function (by evaluation of mean arterial pressure (MAP) variability) in rats (164.5 + 1.7 g) 7, 14, 30 and 120 days after streptozotocin (STZ) injection, treated with insulin, using measurements of arterial pressure, HR and MAP variability. HR variability was evaluated by the standard deviation of RR intervals (SDNN) and root mean square of successive difference of RR intervals (RMSSD). MAP variability was evaluated by the standard deviation of the mean of MAP and by 4 indices (P1, P2, P3 and MN) derived from the three-dimensional return map constructed by plotting MAPn x [(MAPn+1) - (MAPn)] x density. The indices represent the maximum concentration of points (P1), the longitudinal axis (P2), and the transversal axis (P3) and MN represents P1 x P2 x P3 x 10(-3), STZ induced increased urinary glucose in diabetic (D) rats compared to controls (C). Seven days after STZ, diabetes reduced resting HR from 380.6 + 12.9 to 319,2 + 19.8 bpm, increased HR variability, as demonstrated by increased SDNN, from 11.77 + 1.67 to 19.87 + 2.60 ms, did not change MAP, and reduced P1 from 61.0 + 5.3 to 51.5 + 1.8 arbitrary units (AU), P2 from 41.3 + 0.3 to 29.0 + 1.8 AU, and MN from 171.1. + 30.2 to 77.2 + 9.6 AU of MAP. These indices, as well as HR and MAP, were similar for D and C animals 14, 30 and 120 days after STZ. Seven-day rats showed a negative correlation of urinary glucose with resting HR (r=-0.76, P=0.03) as well as with the MN index (r=-0.83, P=0.01). We conclude that rats with short-term diabetes mellitus induced by STZ presented modified autonomic control of HR and MAP which was reversible. The metabolic control may influence the results, suggesting that insulin treatment and a better metabolic control in this model may modify arterial pressure, HR and MAP variability.
Assuntos
Ratos , Animais , Masculino , Pressão Sanguínea , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Modelos Animais de Doenças , Frequência Cardíaca , Insulina/farmacologia , Ratos Wistar , Estreptozocina/farmacologiaRESUMO
Autonomic neuropathy is a frequent complication of diabetes associated with higher morbidity and mortality in symptomatic patients, possibly because it affects autonomic regulation of the sinus node, reducing heart rate (HR) variability which predisposes to fatal arrhythmias. We evaluated the time course of arterial pressure and HR and indirectly of autonomic function (by evaluation of mean arterial pressure (MAP) variability) in rats (164.5 +/- 1.7 g) 7, 14, 30 and 120 days after streptozotocin (STZ) injection, treated with insulin, using measurements of arterial pressure, HR and MAP variability. HR variability was evaluated by the standard deviation of RR intervals (SDNN) and root mean square of successive difference of RR intervals (RMSSD). MAP variability was evaluated by the standard deviation of the mean of MAP and by 4 indices (P1, P2, P3 and MN) derived from the three-dimensional return map constructed by plotting MAPn x [(MAPn + 1)-(MAPn)] x density. The indices represent the maximum concentration of points (P1), the longitudinal axis (P2), and the transversal axis (P3) and MN represents P1 x P2 x P3 x 10(-3). STZ induced increased urinary glucose in diabetic (D) rats compared to controls (C). Seven days after STZ, diabetes reduced resting HR from 380.6 +/- 12.9 to 319.2 +/- 19.8 bpm, increased HR variability, as demonstrated by increased SDNN, from 11.77 +/- 1.67 to 19.87 +/- 2.60 ms, did not change MAP, and reduced P1 from 61.0 +/- 5.3 to 51.5 +/- 1.8 arbitrary units (AU), P2 from 41.3 +/- 0.3 to 29.0 +/- 1.8 AU, and MN from 171.1 +/- 30.2 to 77.2 +/- 9.6 AU of MAP. These indices, as well as HR and MAP, were similar for D and C animals 14, 30 and 120 days after STZ. Seven-day rats showed a negative correlation of urinary glucose with resting HR (r = -0.76, P = 0.03) as well as the MN index (r = -0.83, P = 0.01). We conclude that rats with short-term diabetes mellitus induced by STZ presented modified autonomic control of HR and MAP which was reversible. The metabolic control may influence these results, suggesting that insulin treatment and a better metabolic control in this model may modify arterial pressure, HR and MAP variability.
Assuntos
Pressão Sanguínea , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Frequência Cardíaca , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Animais , Masculino , Ratos , Ratos Wistar , Fatores de TempoRESUMO
Previous data showed that diabetes induced by streptozotocin for 5 days causes changes in arterial pressure control and baroreflex regulation of heart rate in male Wistar rats. The impairment of baroreflex may be related to autonomic neuropathy as described by several investigators. The aim of this study was to identify autonomic changes in short-term experimental diabetes in rats (induced for 5 days with streptozotocin 65 mg IP). Intra-arterial blood pressure signals were obtained from 6 control group and 7 diabetic group rats and processed in a data acquisition system (CODAS, 1 kHz). Both vagal and sympathetic function were assessed through intravenous injections of methylatropine and propranolol. Streptozotocin induced hyperglycemia (18.9 +/- 1.8 versus 5.8 +/- 0.2 mmol/L) and reductions in mean arterial pressure (102 +/- 2 versus 117 +/- 3 mm Hg) and resting heart rate (298 +/- 14 versus 332 +/- 2 beats per minute). Sodium and potassium levels were not different between groups. The intrinsic heart rate was reduced in the diabetic group (302 +/- 10 versus 398 +/- 6 beats per minute). This group also exhibited depressed vagal and sympathetic tone (50% and 22%, respectively), reduction of vagal effect (42%), and no change in sympathetic effect. In conclusion, early autonomic dysfunction in short-term streptozotocin-induced diabetes seems to be related to changes in arterial pressure and baroreflex control.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Animais , Antibacterianos , Derivados da Atropina , Barorreflexo/fisiologia , Pressão Sanguínea , Frequência Cardíaca , Masculino , Parassimpatolíticos , Propranolol , Ratos , Ratos Wistar , Estreptozocina , Sistema Nervoso Simpático/fisiopatologia , Simpatolíticos , Fatores de Tempo , Nervo Vago/fisiologiaRESUMO
Although an increased prevalence of hypertension is associated with insulin-dependent diabetes, little is known about the effect of streptozotocin (STZ) diabetes on arterial pressure (AP) regulation in rats. Changes in AP induced by STZ, as well as associated factors in blood pressure regulation such as baroreflex sensitivity, plasma renin activity (PRA), plasma glucose and insulin levels and endothelium participation, were studied in male Wistar rats weighing 287 +/- 10 g. The same seven conscious rats were used for all measurements before and after STZ diabetes. AP pulses were stored on a videotape recorder and processed by a data acquisition system. Baroreflex sensitivity was evaluated by measuring heart rate (HR) changes induced by AP variations produced by phenylephrine and sodium nitroprusside injection. The effect of inhibition of nitric oxide synthesis with NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg i.v. bolus plus infusion at 20 mg kg-1 h-1) on AP was evaluated in another set of rats (6 normal and 5 submitted to STZ treatment). STZ induced hyperglycemia (306 +/- 19 mg/dl), a reduction in mean arterial pressure (MAP, from 116 +/- 5 to 101 +/- 4 mmHg) and no changes in HR (320 +/- 10 vs 298 +/- 14 bpm). The tachycardic response to arterial pressure decreases was impaired (-2.29 +/- 0.5 vs -4.5 +/- 0.7 bpm/mmHg, in control) while the bradycardic response to arterial pressure increases was unchanged. Pressure responsiveness to phenylephrine was impaired after STZ (3.78 +/- 0.4 vs 6.73 +/- 0.8 mmHg microU-1 ml-1, in control).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Barorreflexo , Pressão Sanguínea , Diabetes Mellitus Experimental/fisiopatologia , Animais , Barorreflexo/efeitos dos fármacos , Glicemia/análise , Pressão Sanguínea/efeitos dos fármacos , Cardiotônicos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Insulina/sangue , Masculino , Fenilefrina/farmacologia , Ratos , Ratos Wistar , Renina/sangueRESUMO
Although an increased prevalence of hypertension is associated with insulin-dependent diabetes, little is known about the effect of streptozotocin (STZ) diabetes on arterial pressure (AP) regulation in rats. Changes in AP induced by STZ, as well as associated factors in blood pressure regulation such as baroreflex sensitivity, plasma ren activity (PRA), plasma glucose and insulin levels and endothelium participation, were studied in male Wistar rats weighing 287 + or - 10 g. The same seven conscious rats were used for all measurements before and after STZ diabetes. AP pulses were stored on a videotape recorder and processed by a data acquisition system. Baroreflex sensitivity was evaluated by measuring heart rate (HR) changes induced by AP variations produced by phenylephrine and sodium nitroprusside injection. The effect of inhibition of nitric oxide synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg iv bolus plus infusion at 20 mg kg-1h-1) on AP was evaluated in another set of rats (6 normal and 5 submitted to STZ treatment). STZ induced hyperglycemia (306 + or - 19 mg/dl), a reduction in mean arterial pressure (MAP, from 116 + or - 5 to 101 + or - 4 mmHg) and no changes in HR (320 + or - 10 vs 298 + or - 14 bpm). The tachycardic response to arterial pressure decreases was impaired (-2.29 + - 0.5 vs -4.5 + or - 0.7 bpm/mmHg, in control) while the bradycardic response to arterial pressure increases was unchanged. Pressure responsiveness to phenylephrine was impaired after STZ (3.78 + or - 0.4 vs 6.73 + or - 0.8 mmHg µU-1 ml-1, in control). Plasma insulin (6.7 + or - 0.6 vs 5.3 + - 1.2 µU/ml) and PRA (6.8 + or - 0.8 vs 7.9 + or - 1.6 ng ANGI ml-1h-1) were similar before and after STZ. L-NAME induced similar increases in normal (+44.67 + or - 0.41 mmHg) and STZ-diatetic rats (+46.50 + or - 15 mmHg). These data show that 5-day STZ diabetes decreases AP and induces impairment of baroreflex sensitivity. These changes do not seem to be related to plasma insulin levels, PRA or nitric oxid synthesis