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

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.

Associations Between Metabolic Profiles and Target-Organ Damage in Chinese Individuals With Primary Aldosteronism

“…Consistent with previous studies (4,23), our study showed that compared to matched EH controls, PA patients exhibited more renal damage indicated by reduced eGFR and greater prevalence of microalbuminuria, as well as more cardiac damage indicated by an increased prevalence of LVH. On the one hand, there is accumulating evidence including our previous researches, which support that many detrimental effects of aldosterone excess are involved in causing pre-clinical TOD in the PA patients; they include inflammation, oxidative stress, endothelial dysfunctions, and vascular calcification (7,(24)(25)(26)(27). On the other hand, a majority of patients with MetS, a cluster of risk factors, tend to develop structural and functional abnormalities of target organs, which precede cardiovascular complications (28,29).…”

Review of Markers of Zona Glomerulosa and Aldosterone-Producing Adenoma Cells

“…59 An involvement of this pathway is consistent with the increased levels of NOx2 and p22phox, which forms the catalytic core of NADPH, in APA patients. 60,61 While probably relevant for the pathophysiology of APA, the lack of data currently precludes use of either NRF2, or NADPH as markers of aldosterone-producing cells.…”