Alterações de Parâmetros Cardiovasculares e Envolvimento dos Receptores AT2 na CVLM sobre a Pressão Arterial, induzidas por Atividade Física de Baixa Intensidade em Ratos com Hipertensão Renovascular

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

10 Low intensity physical activity has been used as a non-pharmacological treatment for hypertension. The caudal vetrolateral medulla (CVLM) represents the major tonic inhibitory afferece to the rostral ventrolateral medulla (RVLM). Regarding hypertensive states, CVLM neurons seem to be inefficient in counteracting the increased intrinsic pressor activity of the RVLM neurons. The 2K1C renovascular hypertensive experimental model exhibit high plasmatic levels of renin and angiotensin II (Ang II). The present study aimed and evaluated the involvement of the renin-angiotensin system (RAS) in the blood pressure (BP) control mechanisms, in the sensitivity of the baroreflex bradycardia and in the reactivity of the CVLM neurons to Ang II (40 ng) and to the selective AT2 receptor antagonist PD123319 (50 ng) in sedentary or trained normotensive or hypertensive (2K1C). Fisher rats (weighting 150 to 200 g) were anesthetized by a mixture of Ketamine (50 mg/ Kg, i.p.) and xylazine (5 mg/ Kg, i.p.) for the placement of the silver clip around the left renal artery or for Sham surgery and were separated in two groups: sedentary or low intensity trained (swimming) one hour per day, five days per week, during four weeks. The BP was measured in trained and sedentary animals every training day throught tail cuff method. 30 days after the surgeries, the 2K1C and Sham animals (sedentary and trained) were anesthetized with urethane (1.2 g/ Kg, i.p.), placed onto a stereotaxic apparatus, had the medulla exposed and were intrumented for mean arterial pressure (MAP) and heart rate (HR) measurements. The baroreflex bradycardia sensitivity was assessed trough i.v. bolus injection of phenylephrine. At the end of the experiments the animals underwent decapitation and had the brain, kidneys and hearts collected. Some of these organs were weightened (dry organ weight/ body weight) and another part was sent for histological analisys. The tail cuff method showed that the 2K1C sedentary (105 2 mmHg, n=11) and 2K1C trained group (118 4 mmHg, n=17) presented higher BP levels when compared to the sedentary Sham group (93 3 mmHg, n=12) after the first week after surgery and on the second and third weeks as well. On the fourth week after surgeries the BP levels of the sedentary hypertensive (153 6 mmHg, n=11) and trained groups (129 4 mmHg, n=17) were higher in comparison to the Sham sedentary group (103 3 mmHg, n=12). However, in the 2K1C group we observed a significative reduction in the BP levels of the trained group in comparison to the trained hypertensive group. The percentage of mass reduction in the clipped kidney were similar among 2K1C sedentary (-27 7 %, n=5) and 2K1C trained (-39 9 %, n=8) groups and increased when compared to Sham groups. The histological analisys showed that the pathological changes (such as glomerual sclerosis and inflammation) of the clipped (left) kidney of Sham sedentary animals appear to be reduced 11 in the Sham trained group. Meanwhile, the 2K1C trained rats presented congestion, tubular focal degeneration, fibrosis, inflammation and tubular dilation reduced in comparison to the sedentaries 2K1C rats. Regarding the histological analisys of the non-clipped kidney (right), we observed reduced congestion, glomeruar sclerosis and inflamation and increased focal tubular degeneration and tubular dilation in the Sham trained group in comparison to the Sham sedentary group. The dry heart weight from 2K1C animals (sedentary and trained) were statisticaly similar and higher than the dry heart weight from sham sedentary animals. However, it was observed an increased ventricular mass of the hearts of 2K1C sedentary and trained animals that has not occurred to the ventricles of Sham trained animals. The histological analisys of the cardiac structures showed a reduction in the cardiac muscle cells degeneration and excentric ventricular wall thickening in sham trained in comparison to sham sedentary animals. It was also observed that in the 2K1C trained group a reduction in the ventricular and vascular wall thickening, a reduction in the fibrosis and increased focal ventricular degeneration and inflammation when compared to 2K1C sedentary group. Regarding water consumption, 2K1C sedentary animals presented an increased ingestion until the fourth week after surgery; while the 2K1C trained animals reduced the water ingestion in the fourth week after surgery. The Sham trained animals presented an increased ingestion of water increased only during the first and second weeks of swimming. The urea serum levels were significantly higher in trained animals (Sham and 2K1C). The basal MAP levels of 2K1C sedentary group was significantly higher compared to Sham sedentary group (161 13.5 mmHg; n=5 vs 105 4.3 mmHg; n=6, respectively). The physical training significantly reduced the MAP levels of the 2K1C trained group (127 6 mmHg; n=7) and these values were statisticaly different from 2K1C sedentary and Sham (trained and sedentary) groups. The basal HR values of the Sham trained group (375 8 bpm; n=7) were not significantly different from the sham sedentary group (400 13 bpm; n=6). Nevertheless, the basal HR of the 2K1C trained group were significantly reduced when compared to 2K1C sedentary group (407 12 bpm; n=5). The baroreflex bradycardia was significantly reduced in the 2K1C sedentary group in comparison to the Sham sedentary group (0.36 0.07 ms/ mmHg, n=6). There were no significative differences in the baroreflex bradycardia among Sham (sedentary and trained) groups. On the other hand, 2K1C trained group presented an increased baroreflex bradycardia in comparison to 2K1C sedentary animals (0.2 0.03 ms/ mmHg, n=7 vs 0.09 0.03 ms/ mmHg; n=5, respectively). The baroreflex sensitivity measured in the 2K1C trained group was similar to that observed in the 2K1C sedentary rats. The microinjection of Ang II into the CVLM was able to reduce the MAP of 2K1C groups to the levels observed in the Sham groups (-13 1 mmHg, n=6; sedentary and -13 2 mmHg, n=7; trained). Surprisingly, the microinjection of the selective AT2 receptor antagonist, PD123319, into the CVLM produced a hypotensive effect in the 2K1C sedentary group (-10 1 mmHg), that was significantly different from the vehicle microinjections into the same site (-5 1 mmHg, n=5). In a different fashion, 2K1C trained rats presented a hypotensive effect in response to the PD123319 microinjection into the CVLM that was similar to that observed after the saline microinjection. The hypotensive effect in response to microinjection of Ang II into the CVLM was blunted by the prior PD123319 microinjection into the CVLM in all groups tested. The results of the present study showed that low-intensity physical activity, that is effective in reducing high BP and in restoring the sensitivity of the baroreflex bradycardia, does not induce changes in the responsiveness to Ang II at CVLM of normotensive or hypertensive, 2K1C rats. Concerning the later results, on the order hand, changes in the responsiveness to AT2 related stimuli at the CVLM appears to be involved in the cardiovascular effect of low-intensity physical activity and add new and significant insights into RAS mechanisms involved in cardiovascular homeostasis and in its adaptation to exercise in renovascular hypertension.

ASSUNTO(S)

envolvimento dos receptores atividade física pressão arterial hipertensão cardiovasculares bioquimica

ACESSO AO ARTIGO

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