RESUMO
The epidemiologically important Mycobacterium tuberculosis Beijing genotype strains, highly endemic in East Asia, have become an emerging infection in certain geographic areas, including Russia, because of its increasing prevalence and association with multidrug resistance (MDR). The aim was to verify whether MDR Beijing strains circulating in the emerging regions present some biological particularities that could contribute to their success in causing disease in comparison with the sporadic strains from locations with low prevalence of the Beijing genotype. We evaluated virulence-associated characteristics of the MDR Beijing strains isolated in Russia and compared them with those of the drug-resistant and susceptible Beijing strains from Brazil and reference H37Rv strain. We found that Russian MDR strains demonstrated an increased bacterial fitness and growth in THP-1 macrophage-like cells, as well as a higher capacity to induce non-protective cytokine synthesis and necrotic macrophage death. By contrast, the biological properties of the strains isolated in Brazil largely resembled those of the H37Rv strain, with the exception of the drug-resistant isolates that presented significantly reduced fitness. The data demonstrate that the emerging MDR strains of the Beijing genotype circulating in Russia do express a pattern of properties associated with the enhanced virulence favouring its clonal dissemination in this region.
Assuntos
Doenças Transmissíveis Emergentes/microbiologia , Mycobacterium tuberculosis/fisiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adolescente , Adulto , Análise de Variância , Brasil/epidemiologia , Morte Celular , Linhagem Celular , Doenças Transmissíveis Emergentes/epidemiologia , Citocinas/metabolismo , Feminino , Genótipo , Humanos , Macrófagos/metabolismo , Macrófagos/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/patogenicidade , Federação Russa/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Virulência/genéticaRESUMO
The time-course of changes in renal sympathetic nerve activity (RSNA), arterial and cardiopulmonary baroreflexes sensitivities was evaluated in conscious rats eight hours (8 h) and ten days (10 day) after myocardial infarction (MI), induced by coronary artery ligation. RSNA was recorded by a platinum electrode implanted in left renal nerve. Arterial and cardiopulmonary baroreflexes sensitivities were evaluated by changes in blood pressure and serotonin administration, respectively. Both 8 h and 10 day groups presented hypotension (103+/-4 vs. 102+/-2 vs. 115+/-4 mm Hg), but only 8 h showed tachycardia (422+/-22 vs. 378+/-11 vs. 384+/-9 bpm) when compared to Control rats. RSNA was depressed 8 h after MI and increased in 10 day group (12+/-2 vs. 39+/-8 vs. 22+/-2 mV/cycle). Although arterial baroreflex control of heart rate was similar in all groups, the arterial baroreflex control of RSNA in 8 h group was impaired during reductions (-0.35+/-0.10 vs. -1.66+/-0.23 vs. -0.09+/-0.14 mV/cycle/mm Hg) or increases (-0.77+/-0.17 vs. -1.63+/-0.58 vs. -1.66+/-0.17 mV/cycle/mm Hg) in blood pressure when compared to Control animals. Moreover, cardiopulmonary baroreflex bradycardic response was increased in 8 h rats and normalized in 10 day group. The results suggest that the increased cardiopulmonary baroreflex sensitivity in 8 h may contribute to the reduction in the tonic level of RSNA as well as in the impairment of the baroreflex control of RSNA in the presence of hypotension.
Assuntos
Barorreflexo/fisiologia , Infarto do Miocárdio/fisiopatologia , Artéria Renal/inervação , Fibras Simpáticas Pós-Ganglionares/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Hipotensão/fisiopatologia , Masculino , Ratos , Ratos Wistar , Renina/sangue , Serotonina/metabolismo , Serotonina/farmacologia , Taquicardia/fisiopatologiaRESUMO
Aging is associated with altered autonomic control of cardiovascular function, but baroreflex function in animal models of aging remains controversial. In this study, pressor and depressor agent-induced reflex bradycardia and tachycardia were attenuated in conscious old (24 mo) rats [57 and 59% of responses in young (10 wk) Wistar rats, respectively]. The intrinsic heart rate (HR, 339 +/- 5 vs. 410 +/- 10 beats/min) was reduced in aged animals, but no intergroup differences in resting mean arterial blood pressure (MAP, 112 +/- 3 vs. 113 +/- 5 mmHg) or HR (344 +/- 9 vs. 347 +/- 9 beats/min) existed between old and young rats, respectively. The aged group also exhibited a depressed (49%) parasympathetic contribution to the resting HR value (vagal effect) but preserved sympathetic function after intravenous methylatropine and propranolol. An implantable electrode revealed tonic renal sympathetic nerve activity (RSNA) was similar between groups. However, old rats showed impaired baroreflex control of HR and RSNA after intravenous nitroprusside (-0.63 +/- 0. 18 vs. -1.84 +/- 0.4 bars x cycle(-1) x mmHg(-1) x s(-1)). Therefore, aging in rats is associated with 1) preserved baseline MAP, HR, and RSNA, 2) impaired baroreflex control of HR and RSNA, and 3) altered autonomic control of resting HR.
Assuntos
Envelhecimento/fisiologia , Barorreflexo/fisiologia , Frequência Cardíaca/fisiologia , Rim/inervação , Sistema Nervoso Simpático/fisiologia , Animais , Pressão Sanguínea , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Ratos , Ratos Wistar , Simpatomiméticos/farmacologia , Sístole , Nervo Vago/fisiologiaRESUMO
Exercise training attenuates arterial hypertension and increases baroreflex sensitivity in spontaneous hypertension. However, no information exists regarding the portion of the baroreflex arch in which this attenuation takes place. We tested the hypothesis that exercise training increases the afferent pathway sensitivity of baroreflex control in both normotensive and spontaneously hypertensive rats (SHR). Arterial pressure and whole-nerve activity of the aortic baroreceptor (multifiber preparation) were evaluated in 30 male rats assigned to 4 groups: sedentary and exercise-trained normotensive rats and sedentary and exercise-trained SHR. Exercise training was performed on a motor treadmill, 5 d/wk for 60 minutes, gradually progressing toward a speed of 26.8 m/min. Exercise training reduced mean arterial pressure in conscious exercise-trained SHR (183+/-4 versus 165+/-7 mm Hg). The relation between changes in aortic baroreceptor discharge and changes in systolic arterial pressure increased significantly in exercise-trained normotensive rats (2.09+/-0.1 versus 1.44+/-0.1%/mm Hg) and exercise-trained SHR (0.92+/-0.1 versus 0.71+/-0.1%/mm Hg) compared with their respective sedentary rats. Likewise, the average aortic baroreceptor gain sensitivity (calculated by logistic equation) was significantly higher in exercise-trained normotensive rats (2.25+/-0.19 versus 1.77+/-0.03%/mm Hg) and exercise-trained SHR (1.07+/-0.04 versus 0.82+/-0.05%/mm Hg) compared with their respective sedentary control rats. In conclusion, exercise training increases aortic baroreceptor gain sensitivity in normotensive and SHR, thus improving baroreceptor sensitivity, which may result in a more efficient arterial pressure regulation by the baroreflexes.
Assuntos
Hipertensão/fisiopatologia , Condicionamento Físico Animal/fisiologia , Pressorreceptores/fisiologia , Vias Aferentes/fisiopatologia , Animais , Aorta/metabolismo , Pressão Sanguínea , Frequência Cardíaca , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos WistarRESUMO
The aging process is associated with alterations in the autonomic control of cardiovascular function. In the present study, we observed that reflex bradycardia and tachycardia produced by pressor and depressor agents were attenuated in old (24 mo) rats [70 and 56% of responses in young rats (4 mo), respectively]. In contrast, the bradycardia induced by chemoreflex activation with increasing doses of KCN (60, 100, 140, and 180 micrograms/kg) was greater in old [-30 +/- 19, -155 +/- 32, -198 +/- 15, and -204 +/- 24 beats/ min (bpm)] than in young rats [-13 +/- 6, -75 +/- 20 (P < 0.05), -99 +/- 26 (P < 0.05), and -103 +/- 20 (P < 0.05) bpm]. The chemoreflex-pressor responses tended to be greater in old (12 +/- 6, 47 +/- 6, 54 +/- 7, and 55 +/- 5 mmHg) than in young rats (4 +/- 2, 32 +/- 8, 42 +/- 6, and 44 +/- 4 mmHg), but the differences between both groups were not statistically significant. However, pressor responses were higher in old rats after the chemoreflex-activated bradycardia was attenuated by atropine (4 mg/kg iv) [old (17 +/- 9(1) P < 0.05; 57 +/- 4, P < 0.05; 61 +/- 4; and 64 +/- 5 mmHg) vs. young (3 +/- 2, 29 +/- 9(1) 50 +/- 5, and 58 +/- 7 mmHg)]. Administration of the alpha 1-blocker prazosin (1 mg/kg iv) blunted pressor responses but did not change the bradycardia induced by chemoreflex in both groups. In conclusion, our data indicate that the bradycardia and pressor responses to chemoreflex activation were exaggerated, whereas the heart rate responses (bradycardia and tachycardia) to baroreflex were depressed in old rats.
Assuntos
Envelhecimento/fisiologia , Barorreflexo/fisiologia , Fenômenos Fisiológicos Cardiovasculares , Células Quimiorreceptoras/fisiologia , Reflexo/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Frequência Cardíaca/efeitos dos fármacos , Injeções Intravenosas , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Cianeto de Potássio/farmacologia , Ratos , Ratos WistarRESUMO
O objetivo desse estudo foi avaliar a atividade neurogênica dos pressoreceptores (APR, registrada no nervo aórtico) e a atividade simpática periférica (ASR, registrada no nervo simpático renal), considerando-se a ocorrência e distribuição nos ciclos cardíacos e nas fases sistólica e diastólica. Foram estudados ratos normais anestesiados e ratos acordados submetidos à desnervação sino-aórtica (DSA) nas fases aguda e crônica após a desnervação. Os resultados obtidos sugerem que a falta de sincronismo entre a atividade simpática e os ciclos da pressão arterial contribuem para as alterações encontradas na pressão sanguínea na ausência dos pressoreceptores
Abstract - The aim of this study was to analyze the neurogenic activity of baroreceptors (recorded on the aortic nerve, APR) and peripheral sympathetic activity (recorded on the renal nerve. AsR ) with regard to its occurence and distribution in relation to the cardiac cycle and the systolic and diastolic phases of it. Normal anesthetized rats and awaken sino aortic denervated (SAD) rats were studied. The analysis showed that the existing synchronism between sympathetic activity and arterial pressure pulses found in normal rats was absent in SAD rats. These results suggest that the Jack of synchronism between sympathetic activity and cardiac cycles may contribute to the alterations in blood pressure observed in the absence of baroreceptors
Assuntos
Pressorreceptores/fisiologia , Nervos Periféricos , Pressão Arterial/fisiologia , Sistema Nervoso Simpático , Anestesia , Pressão AtmosféricaRESUMO
The arterial pressure level attained in sinoaortic denervated rats depends on the net effect of eliminating excitatory and inhibitory influences (chemoreceptor and baroreceptor elimination, respectively). After sinoaortic denervation is completed, the hypertension usually observed within the first few days is followed by normotension at the chronic stages. In this work renal sympathetic nerve activity was measured in conscious, unrestrained rats 6 hours (acute) and 20 days (chronic) after sinoaortic denervation. Increased arterial pressure (154 +/- 10 versus 114 +/- 3 mm Hg in controls) and renal sympathetic nerve activity (32 +/- 5 versus 13 +/- 2 bars per cycle in controls) with no changes in heart rate (404 +/- 17 vs 380 +/- 26 beats per minute) were observed in rats with acute sinoaortic denervation. In rats with chronic sinoaortic denervation, arterial pressure (119 +/- 8 mm Hg) and renal sympathetic nerve activity (13 +/- 6 bars per cycle) returned to control levels. Bradycardiac and tachycardiac responses to changes in blood pressure were reduced to 88% and 89%, respectively, in rats with acute sinoaortic denervation and 76% and 74%, respectively, in rats with chronic sinoaortic denervation. The reflex control of renal sympathetic nerve activity after acute and chronic sinoaortic denervation showed an impairment of sympathoinhibition (0.13 +/- 0.02 and 0.25 +/- 0.1 bars per cycle, respectively, versus 0.9 +/- 0.17 bars per cycle in controls). Sympathoexcitatory responses also were impaired in rats with acute and chronic sinoaortic denervation (0.08 +/- 0.03 and 0.37 +/- 0.1 bars per cycle, respectively, compared with 0.98 +/- 0.2 bars per cycle in controls).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Barorreflexo/fisiologia , Pressão Sanguínea , Hipertensão/fisiopatologia , Rim/inervação , Sistema Nervoso Simpático/fisiologia , Análise de Variância , Animais , Denervação , Frequência Cardíaca , Masculino , Monitorização Fisiológica , Ratos , Ratos WistarRESUMO
High-renin hypertensive rats exhibit a general impairment of the baroreceptor reflexes. In the present study we compared the effect of the angiotensin converting enzyme inhibitor captopril (10 mg/kg per day) with the effect of the selective angiotensin subtype 1 receptor blocker DuP 753 (10 mg/kg per day) on the baroreceptor reflex bradycardia (progressive doses of phenylephrine) and baroreceptor reflex tachycardia (progressive doses of nitroprusside) in conscious rats 7 days after aortic ligation. Arterial pressure was markedly reduced after both acute (15-minute) treatment with captopril (123 +/- 6 versus 184 +/- 23 mm Hg) and DuP 753 (140 +/- 10.5 versus 181 +/- 5.4 mm Hg), but the depressed baroreceptor reflex bradycardia increased only after DuP 753 (1.13 +/- 0.22 versus 0.75 +/- 0.60 beats per minute [bpm]/mm Hg) and remained attenuated after captopril (0.54 +/- 0.086 versus 0.30 +/- 0.07 bpm/mm Hg). After a 2-day treatment, captopril reduced arterial pressure (95 +/- 5 versus 184 +/- 2.3 mm Hg) to lower levels than DuP 753 (119 +/- 6 versus 172 +/- 4.6 mm Hg), whereas the depressed baroreceptor reflex bradycardia remained unchanged with captopril (0.46 +/- 0.13 versus 0.31 +/- 0.076 bpm/mm Hg) and increased with DuP 753 (1.13 +/- 0.19 versus 0.38 +/- 0.12 bpm/mm Hg). Neither DuP 753 nor captopril administered acutely (15 minutes) or for 2 days significantly altered the depressed baroreceptor reflex tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Angiotensina II/antagonistas & inibidores , Compostos de Bifenilo/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Captopril/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/fisiopatologia , Imidazóis/farmacologia , Pressorreceptores/fisiopatologia , Renina/sangue , Tetrazóis/farmacologia , Animais , Hipertensão/sangue , Losartan , Masculino , Fenilefrina/farmacologia , Pressorreceptores/efeitos dos fármacos , Pressorreceptores/fisiologia , Ratos , Ratos Wistar , Reflexo , Fatores de TempoRESUMO
We studied the correlation of changes in gain sensitivity of the baroreceptors and the development of resetting of the baroreceptors 2 and 6 days after the onset of hypertension produced by subdiaphragmatic aortic constriction in rats. Mean arterial pressure of anesthetized rats was maintained at approximately the same level as that of conscious rats, and baroreceptor function curves were studied on a beat-to-beat basis by computer. After 2 days of hypertension, the difference between the systolic pressure threshold and the control diastolic pressure was -13 +/- 2 mm Hg (125 +/- 3 versus 138 +/- 4 mm Hg). Individual values showed that in seven of nine hypertensive rats, the difference was less than 15 mm Hg, indicating complete resetting. After 6 days of hypertension, all rats exhibited complete resetting, when the systolic pressure threshold was similar to control diastolic pressure (143 +/- 4 versus 141 +/- 2 mm Hg), indicating that more than 2 days of hypertension is necessary for full displacement of the pressure thresholds when all hypertensive rats are considered. Slopes of the baroreceptor curves after 2 and 6 days of hypertension showed that baroreceptor gain was depressed by 25% and 34%, respectively. The difference was not statistically significant (1.07 +/- 0.054% versus 0.94 +/- 0.049% and 1.43 +/- 0.075% in controls). When changes in pressure were circumscribed to a more physiological range, a depression of 25% in response to +10 mm Hg and 37% in response to -10 mm Hg was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Hipertensão/fisiopatologia , Pressorreceptores/fisiopatologia , Animais , Pressão Sanguínea/fisiologia , Masculino , Pressorreceptores/fisiologia , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
The extent and characteristics of reversal of baroreceptor resetting after pressure normalization were studied in rats with renal hypertension of 2 months' duration. During the control period, the displacement of the entire baroreceptor function curve was accompanied by a decrease slope, indicating that the gain sensitivity was depressed by 36% in the renal hypertensive rats. In response to changes of +10 and -10 mm Hg in the control pressure, the gain sensitivity was attenuated by 56% and 42%, respectively. Two minutes after unclipping and bleeding when necessary, mean arterial pressure decreased from 171 +/- 11 to 134 +/- 11 mm Hg and remained at approximately the same level for the 2-hour period of observation. The extent of reversal of the mean pressure threshold for activation of the baroreceptors was approximately constant (approximately 60%) in the time range of 2-120 minutes. The extent of reversal was slightly higher when the changes in systolic pressure threshold divided by the total change in control diastolic pressure were calculated (maximal of 83%). During the first 20 minutes, the displacements of the curves were parallel with no change in the depressed gain sensitivity. Complete normalization of gain sensitivity was observed after 90-120 minutes. The data indicate that, within the first 2 hours of pressure normalization of chronic renal hypertensive rats, 1) reversal of the resetting of pressure threshold is pronounced (60-80%) but still incomplete and 2) gain sensitivity returns completely to normal.
Assuntos
Hipertensão Renal/fisiopatologia , Pressorreceptores/fisiopatologia , Animais , Pressão Sanguínea/fisiologia , Limiar Diferencial , Ratos , Ratos EndogâmicosRESUMO
The characteristics and extent of rapid or acute resetting of the aortic baroreceptors were studied in long-term renal hypertensive rats during 30 minutes of sustained hypertension produced by phenylephrine infusion. The aortic baroreceptors of hypertensive rats exhibited complete resetting to hypertension because during the control period the systolic threshold pressure for activation of the baroreceptors was similar (137 +/- 5 vs. 142 +/- 4 mm Hg) to the control diastolic pressure. Five minutes after onset of hypertension, a resetting of 32% (percent change of mean pressure threshold divided by total change of mean pressure) was demonstrable. The extent of resetting was 39%, 38%, and 41% after 10, 20, and 30 minutes of hypertension, respectively. When the percent change of systolic threshold pressure divided by total change of control diastolic pressure was used to calculate the extent of resetting, similar results were obtained. The extent of displacement of the entire baroreceptor pressure-response curves was similar to that of pressure thresholds. Reversibility of the resetting process was not complete within 30 minutes of pressure normalization after the administration of phenylephrine was interrupted. These data indicate that the characteristics and extent of rapid resetting of the baroreceptors of renal hypertensive rats, which were reset to operate at hypertensive levels, are similar to those previously described in normotensive rats.
Assuntos
Hipertensão Renal/fisiopatologia , Pressorreceptores/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Limiar Diferencial , Masculino , Fenilefrina/farmacologia , Ratos , Ratos EndogâmicosRESUMO
Rapid or acute resetting of the aortic baroreceptors was studied in anesthetized rats during the onset and maintenance of hypertension produced by subdiaphragmatic aortic constriction for up to 6 h. After 2 min of hypertension, the systolic threshold pressure for activation of the baroreceptors increased by 33% of the total 27-mmHg increase of the control diastolic pressure. Maximal resetting of 46 and 52% was demonstrable after 20 and 30 min of hypertension. The shifts in pressure threshold were accompanied by parallel shifts in the entire baroreceptor function curves. After 30 min of hypertension, resetting was only partially (60%) reversed within the 30 min of pressure normalization. Resetting did not progress with time. Six hours after aortic constriction, resetting was only 38% (vs. 32% after 30 min). The data indicate that acute or rapid resetting of the aortic baroreceptors reaches a maximum within 20-30 min (40-50%) and remains stable for up to 6 h, with no apparent change in the baroreceptor gain.
Assuntos
Aorta/fisiopatologia , Hipertensão/fisiopatologia , Pressorreceptores/fisiopatologia , Animais , Pressão Sanguínea , Constrição , Hipertensão/etiologia , Masculino , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
The characteristics of rapid or acute resetting of the aortic baroreceptors were studied in anesthetized rats during 30 minutes of sustained hypertension produced by phenylephrine infusion. Two minutes after the onset of hypertension, a resetting of 26% (ratio of change in systolic threshold pressure to total change in diastolic pressure) was demonstrable. This represents 60% of the maximal resetting (43%) observed after 20 minutes. Thereafter, the magnitude of resetting remained stable. Pressure-nerve activity showed a parallel shift after 2 and 20 minutes of hypertension, with a slight tendency to increased slope at elevated pressures, especially in the baroreceptor function curve analyzed after 2 minutes. These results suggest that in rats, no significant difference exists in the time course for resetting of baroreceptor fibers with low vs. high thresholds. In contrast to other studies, reversibility of the resetting process was not complete within 30 minutes of pressure normalization, and the extent of reversal was no greater than 60%. The data of the present study, taken together with those obtained previously after 6 hours of hypertension, suggest that during the onset and maintenance of hypertension in rat, acute or rapid resetting of the baroreceptors reaches its maximum in 20 minutes (40%) and remains stable for up to 6 hours, with no apparent change in the baroreceptor gain.