Aliskiren Reduces the Adrenal Zona Glomerulosa Apoptosis and Autophagy in Wistar Rats with 2K1C Hypertension.

Veronica S De Matos,Cherley B V Andrade,Jemima F R Da Silva,Kíssila Rabelo,Priscila G Pereira,Bianca Torres Ciambarella,Camila Salata,Alan C N Moraes,Jorge J De Carvalho,Luciana Lontro Alves,Ana L R Do Nascimento,Victor H V De O Araújo,Aline Bonfim Vieira,Tomohiro Katsuya

doi:10.1155/2020/7684849

Abstract

Hypertension is a disease classified as primary or secondary, manifested not only by elevation of blood pressure but also involved in structural and functional changes of target organs. Renal artery stenosis is a leading factor of secondary hypertension, and its progress is associated with overactivation of the renin-angiotensin-aldosterone system (RAAS). Aliskiren is a renin inhibiting drug that suppresses RAAS and culminates in decreased renin release, plasma angiotensin II concentration, and inhibition of aldosterone secretion. In this sense, the aim of the present study was to analyze the structural and ultrastructural morphophysiology of the adrenal glomerular zone, after treatment with aliskiren in Wistar rats with 2K1C hypertension. Parameters as structure and ultrastructure of the adrenal glomerular zone, cellular apoptosis, nuclear cell proliferation, and AT1 receptor expression were analyzed by immunostaining and electron microscopy. Our results showed that the hypertensive animals treated with aliskiren presented a reestablishment of AT1 receptor expression and decrease in apoptosis and autophagy. In addition, treatment with aliskiren improves the cell aspects in the adrenal glomerular zone, evidenced by ultrastructural analysis through preserved nuclei and well-developed mitochondria. Therefore, our evidence suggests that aliskiren has a beneficial effect on the adrenal glomerular zone remodeling in animals with renovascular hypertension.

Highlights

Hypertension is a disease classified as primary or secondary, manifested by elevation of blood pressure and involved in structural and functional changes of target organs
At week 4, when the aliskiren administration started, the animals in the 2 kidneys clip (2K1C) + A group showed a reduction in systolic blood pressure (SBP), and in week 7, the SBP levels of these animals were similar to the SBP levels of the SHAM and SHAM + A animals (123.2 ± 3 mmHg) (Figure 1(A))
Positive anti-Ang II type 1 receptor (AT1R) antibody immunostaining was observed in all experimental groups in the zona glomerulosa of the adrenal gland (Figures 1(B)–1(E)). e SHAM group (Figure 1(B)) presented an area of 0.91 ± 0.17% stained and the SHAM + A group 0.66 ± 0.19% (Figure 1(C)). e 2K1C group (Figure 1(D)) showed a significant increase of AT1R expression (30.01 ± 2.71%), which was reduced in the 2K1C

Summary

Introduction

Hypertension is a disease classified as primary or secondary, manifested by elevation of blood pressure and involved in structural and functional changes of target organs. Aliskiren is a renin inhibiting drug that suppresses RAAS and culminates in decreased renin release, plasma angiotensin II concentration, and inhibition of aldosterone secretion In this sense, the aim of the present study was to analyze the structural and ultrastructural morphophysiology of the adrenal glomerular zone, after treatment with aliskiren in Wistar rats with 2K1C hypertension. Adrenal steroid hormones serve to modulate a wide range of processes that are central to physiologic responses to stress, including energy metabolism, immune response, electrolyte homeostasis, and fluid balance [1] To fulfill these tasks, the adrenal cortex is organized into functionally and histologically distinct zones: the outermost zona glomerulosa (ZG), the intermediate zona fasciculata (ZF), and the innermost zona reticularis (ZR), which are responsible for the production. High blood pressure is already a health problem, with a projected prevalence of about one-third of the world’s population by 2025 [9]

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