Efeito da injeção do composto 21 no bulbo rostroventrolateral de ratos com hipertensão Renovascular 2-Rins-1-Clipe

• Autor(a) principal: Miura, Jessica Lumi Botêlho
• Data de Publicação: 2021
• Tipo de documento: Trabalho de conclusão de curso
• Idioma: por
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://hdl.handle.net/11449/216491
• topic: Receptor AT1; Receptor AT2; hipertensão renovascular; bulbo rostroventrolateral; Composto 21

The rostral ventrolateral medulla (RVLM) is an important region in the regulation of sympathetic nerve activity and blood pressure regulation in rats with renovascular hypertension. Previous studies have demonstrated that intracerebroventricular infusion of angiotensin II type 2 (AT2) receptor non-peptide selective agonist, Coumpound 21 (C21), reduces mean arterial pressure (MAP) in the normotensive rats. It is known that blockade of subtype 1 angiotensin II (AT1) receptors in the RVLM of rats with renovascular hypertension (2-kidney-1-clip; 2K1C) promotes a decrease in mean arterial pressure of approximately 20 mmHg. In this study, we investigated whether the bilateral microinjection of C21 in the RVLM could promote cardiovascular changes in 2K1C rats and also the effects of bilateral microinjection of losartan associated with C21 in the RVLM in rats with 2K1C hypertension. Holtzman rats (initial weight: 150-180 g) with a silver clip around the left renal artery were used to induce 2K1C hypertension and sham rats (normotensive), which underwent the same procedure, but the silver clip was not inserted around the renal artery. In the first protocol, six weeks after insertion of the renal silver clip, stainless steel cannulas were implanted bilaterally in the RVLM and after 7 days, bilateral microinjections of C21 (100 µmol/200 nL) were performed in the RVLM to record the pulsatile arterial pressure (PAP), mean arterial pressure (MAP) and heart rate (HR) for 30 minutes with the animals in free movement. In the second protocol, six weeks after insertion of the renal silver clip, the animals were anesthetized for catheter insertion in the femoral vein and artery. After 24 hours, the animals were anesthetized with urethane (1.4 g/kg of body weight, intravenous) for bilateral microinjection of losartan (1 nmol/200 nL) and after 15 min, C21 (100 µmol/200 nL) in the RVLM. PAP, MAP and HR were recorded before and up to 45 min after drug injections in the RVLM. The MAP of animals with 2K1C hypertension decreased after bilateral microinjection of C21 in the RVLM by approximately 20 mmHg (before-C21: 169 ± 9, vs. after-C21: 152 ± 8 mmHg vs. baseline; p < 0.05) while MAP in sham rats was not altered (before-C21: 104 ± 3, vs. after-C21: 104 ± 3 mmHg). In anesthetized 2K1C rats (MAP: 200 ± 12 mmHg), losartan associated with C21 promoted a total reduction of 63 mmHg in MAP at the end of the record. In normotensive rats, losartan or C21 microinjected into the RVLM did not significantly alter MAP (MAP: 125 ± 5 mmHg). In conclusion our data show that the activation of AT2 receptors by the selective C21 agonist, microinjected bilaterally in the RVLM, is effective in reducing blood pressure only in rats with 2K1C hypertension and the blocking of AT1 receptors by the antagonist losartan associated with the activation of AT2 receptors by the selective agonist C21, produces effects greater than blocking AT1 receptors or activating AT2 receptors alone.