Role of Nox2 and p22phox in Persistent Postoperative Hypertension in Aldosterone-Producing Adenoma Patients after Adrenalectomy.

Xiaojing Geng,Yajuan Deng,Jun Dong,Ying Liang,Tongfeng Luo,Shaoling Zhang,Ting Li,Hailun Lin,Li Yan

doi:10.1155/2016/2395634

Abstract

Adrenal aldosterone-producing adenoma (APA), producing the salt-retaining hormone aldosterone, commonly causes secondary hypertension, which often persists after unilateral adrenalectomy. Although persistent hypertension was correlated with residual hormone aldosterone, the in vivo mechanism remains unclear. NADPH oxidase is the critical cause of aldosterone synthesis in vitro. Nox2 and p22phox comprise the NADPH oxidase catalytic core, serving to initiate a reactive oxygen species (ROS) cascade that may participate in the pathology. mRNAs of seven NADPH oxidase isoforms in APA were evaluated by RT-PCR and Q-PCR and their proteins by immunohistochemistry and Western blotting. NADPH oxidase activity was also detected. Nox2 and p22phox were especially abundant in APA. Particularly higher Nox2 and p22phox gene and protein levels were seen in APA than controls. Significant correlations between Nox2 mRNA and aldosterone synthase (CYP11B2) mRNA (R = 0.66, P < 0.01) and Nox2 protein and baseline plasma aldosterone concentration (PAC) (R = 0.503, P < 0.01) were detected in APA; however, none were found between p22phox mRNA, CYP11B2 mRNA, p22phox protein, and baseline PAC. Importantly, we found that Nox2 localized specifically in hyperplastic zona glomerulosa cells. In conclusion, our results highlight that Nox2 and p22phox may be directly involved in pathological aldosterone production and zona glomerulosa cell proliferation after APA resection.

Highlights

Primary aldosteronism (PA) is characterized clinically by autonomous aldosterone secretion from the adrenal gland, resulting in suppression of rennin secretion, hypokalemia, and hypertension
Adrenal changes of normal adrenocortical tissues, aldosterone-producing adenoma (APA), Nonfunctioning adenoma (NFA), and peritumoral adjacent tissues were observed by histological examinations performed on 4 μm sections stained with hematoxylin-eosinsaffron (HES)
We demonstrated that the NADPH oxidases (Noxs) activity was higher in APA

Summary

Introduction

Primary aldosteronism (PA) is characterized clinically by autonomous aldosterone secretion from the adrenal gland, resulting in suppression of rennin secretion, hypokalemia, and hypertension. NADPH oxidases (Noxs) have been accepted as major sources for ROS in response to a wide range of stimuli, including angiotensin II, TNF, and IL-1β. They render steroidogenic tissues acutely vulnerable to redox imbalance and dysfunction of macromolecules within the adrenocortical cells and other cells [11, 12]. Members of this oxidase family oxidize intracellular NADPH/NADH, allowing electron transport across the membrane and inducing molecular oxygen to superoxide anion (O2∙−) and hydrogen peroxide (H2O2). Our findings provide a theoretical basis for prognostic evaluation and molecular target therapy in persistent hypertension

Materials and Methods

Results

Discussion