Efeitos do bloqueio de receptores AT1 nas alterações cardiovasculares resultantes do acidente vascular hemorrágico experimental no córtex insular de ratos

Abstract

Stroke, a cerebrovascular disease, is the second leading cause of death in the world, besides, patients who survive a stroke, often present different physiological changes. In this sense, investigating strategies that can mitigate the post-stroke consequences, becomes extremely relevant. Among the different brain regions affected is the insular cortex, the damage of which results in serious cardiovascular changes. The renin-angiotensin system has two axes of action; I) angiotensin-converting enzyme (ACE), angiotensin (Ang) II, AT1 receptor, with vasopressor action and II) ECA2, angiotensin (1-7) (Ang- (1-7)), Mas receptor, with actions contrary to axis of Ang II. In the present study, we evaluated the effect of AT1 receptor blockade on cardiovascular changes generated from experimental hemorrhage in the insular cortex of Wistar rats (CEUA UFMG 112/2019). The animals were submitted to stereotaxis to induce experimental hemorrhage in the insular cortex (ICH) on the right side and after three days of treatment with vehicle, NaCl 0.9% (0.1ml / 100g) or losartan (10mg / kg) were registered cardiovascular parameters, heart rate (HR) and mean arterial pressure (MAP). The group submitted to ICH showed a high baseline HR compared to the control (before in the control; 364.71 ± 5.57 bpm vs 422.0 ± 10.29 after hemorrhage; P <0.0001) without significant changes in the baseline values of PAM. Treatment with losartan, AT1 receptor blocker in the HCI group restored HR to baseline values and additionally, decreased baseline blood pressure values (before 111.33 ± 1.66 mmHg vs 98.66 ± 2.33 after losartan; P <0.0001). These effects produced by losartan have been abolished by the treatment associated with A-779, the Mas receptor antagonist. Taken together with previous findings from our laboratory, the present study suggests that AT1 receptors blockade may reduce the impact of cardiac sympathetic activity exacerbation observed after ICH, as well as promoting a reduction in baseline blood pressure values. At least part of the effects obtained by losartan seems to be related to Ang- (1-7) via the Mas receptor. The data from the present study clearly suggest that losartan can minimize cardiovascular risk after ICH.