Influência dos receptores de angiotensina, AT1 e AT2, no órgão subfornical sobre a função barorreflexa em ratos com hipertensão renovascular
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2020-02-28
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Universidade Federal de Goiás
Resumo
Components of the renin angiotensin system (RAS) are present in several regions of the brain
involved in central regulation of blood pressure (BP). Among them, there is the subfornical
organ (SFO), circumventricular organ (OCV) that is outside the blood-brain barrier (BBB) and
that participates in BP regulation. Studies show that in secondary hypertension models, such
as the 2K1C model, there is an increase in ANG II in important regions of BP control, such as
SFO. Thus, our objective was to evaluate whether the pharmacological inhibition of the Type 1 receptor (AT1) and Type 2 receptor (AT2), in SFO, of rats with two kidneys and a clip (2K1C), influences the baroreflex function. For this purpose, male Wistar rats underwent surgery to induce Renovascular Hypertension (HR), which consisted of clipping the renal artery (Group 2K1C) or simulating the placement of the clip (Group Sham). One week after HR surgery and animal recovery, tail plethysmography was performed for 5 weeks to assess the development of hypertension. At the end of 5 weeks, 2K1C and Sham rats were anesthetized with isoflurane in 100% O2 and subjected to cannulation of the fermoral artery, to record Mean Arterial Pressure (MAP) and Heart Rate (HR), cannulation of the femoral vein for
administration of anesthetic and drugs and craniectomy for Losartan nanoinjection (217 mM, 100nL; AT1 receptor antagonist) ANG II (48 pM, 100nL; AT1 receptor agonist), PD123319 (40mM, 100nL; AT2 receptor antagonist) and C21 ( 0.1μM, 100nL; AT2 receptor agonist) in order to evaluate the influence of AT1 and AT2 receptors on SFO in the baroreflex function. The results showed that the model was able to develop HR over 5 weeks, which was not observed in the Sham group (Animals 2K1C: 1st week 152.13 ± 1.31 mm of mercury (mmHg) and 5th week 208, 52 ± 2.77 mmHg; Animals Sham: 1st week 113.92 ± 1.13 mmHg and 5th week 114.90 ± 0.96 mmHg, p <0.05). In addition, animals with HR presented atrophy of the
clipped kidney when compared to the unclipped kidney (right kidney: 0.34 ± 0.01 g / 100g pc and left kidney: 0.52 ± 0.01 g / 100g pc, p < 0.05). Blockade of AT1 receptors in SFO did not promote pressure changes in normotensive animals (Δ: 0.31 ± 2.16 mmHg in relation to baseline); however, in hypertensive animals there was a reduction in BP (Δ: -11.02 ± 0, 22 mmHg, p <0.05 compared to baseline). In the baroreflex sensitivity test, blocking AT1 receptors increased the reflex bradycardia of the 2K1C losartan group (Δ -10.98 ± 0.77 bpm, p <0.05) when compared to the Sham losartan group (Δ -7.60 ± 0.38 bpm) and 2K1C Saline (Δ -8.00 ± 0.26 bpm). AT2 receptor blockade did not promote changes in MAP and improved reflex bradycardia in the 2K1C PD group (Δ -20.12 ± 1.53 bpm, p <0.05) when compared to the Sham PD group (Δ -11.90 ± 1.20 bpm) and 2K1C Saline (Δ -14.37 ± 1.00 bpm). Thus, the present study provides evidence that the angiotensinergic receptors AT1 and AT2 in SFO mediate the baroreflex responses in the 2K1C model through an inhibitory influence on reflex bradycardia. There was no evidence of the participation of the AT1 and AT2 receptor within the SFO in reflex tachycardia.
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GONÇALVES, F. C. Influência dos receptores de angiotensina, AT1 e AT2, no órgão subfornical sobre a função barorreflexa em ratos com hipertensão renovascular. 2020. 50 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Goiás, Goiânia, 2020.