Translational Medicine Centre, Jiangxi University of Chinese Medicine, Nanchang, 330002, Jiangxi, China.
Endocrine. 2024 Feb;83(2):285-301. doi: 10.1007/s12020-023-03566-6. Epub 2023 Oct 17.
Accumulating evidence has demonstrated the existence of extra-adrenal aldosterone in various tissues, including the brain, heart, vascular, adipocyte, and kidney, mainly based on the detection of the CYP11B2 (aldosterone synthase, cytochrome P450, family 11, subfamily B, polypeptide 2) expression using semi-quantitative methods including reverse transcription-polymerase chain reaction and antibody-based western blotting, as well as local tissue aldosterone levels by antibody-based immunosorbent assays. This mini-review highlights the current evidence and challenges in extra-adrenal aldosterone, focusing on intrarenal aldosterone.
A narrative review.
Locally synthesized aldosterone may play a vital role in various physio-pathological processes, especially cardiovascular events. The site of local aldosterone synthesis in the kidney may include the mesangial cells, podocytes, proximal tubules, and collecting ducts. The synthesis of renal aldosterone may be regulated by (pro)renin receptor/(pro)renin, angiotensin II/Angiotensin II type 1 receptor, wnt/β-catenin, cyclooxygenase-2/prostaglandin E2, and klotho. Enhanced renal aldosterone release promotes Na+ reabsorption and K+ excretion in the distal nephron and may contribute to the progress of diabetic nephropathy and salt-related hypertension.
Inhibition of intrarenal aldosterone signaling by aldosterone synthase inhibitors or mineralocorticoid receptor antagonists may be a hopeful pharmacological technique for the therapy of diabetic nephropathy and saltrelated hypertension. Yet, current reports are often conflicting or ambiguous, leading many to question whether extra-adrenal aldosterone exists, or whether it is of any physiological and pathophysiological significance.
越来越多的证据表明，醛固酮不仅存在于肾上腺，还存在于各种组织中，包括脑、心脏、血管、脂肪细胞和肾脏，这主要是基于使用半定量方法（包括逆转录-聚合酶链反应和基于抗体的 Western blot）检测 CYP11B2（醛固酮合酶，细胞色素 P450，家族 11，亚家族 B，多肽 2）表达，以及通过基于抗体的免疫吸附测定法检测局部组织醛固酮水平。这篇综述强调了肾上腺外醛固酮的现有证据和挑战，重点关注肾内醛固酮。
叙述性综述。
局部合成的醛固酮可能在各种生理病理过程中发挥重要作用，尤其是心血管事件。肾脏中局部醛固酮合成的部位可能包括系膜细胞、足细胞、近端肾小管和集合管。肾醛固酮的合成可能受（前）肾素受体/（前）肾素、血管紧张素 II/血管紧张素 II 型 1 受体、wnt/β-连环蛋白、环氧化酶-2/前列腺素 E2 和 klotho 调节。增强的肾醛固酮释放促进远曲小管的 Na+重吸收和 K+排泄，可能导致糖尿病肾病和盐相关高血压的进展。
醛固酮合酶抑制剂或盐皮质激素受体拮抗剂抑制肾内醛固酮信号可能是治疗糖尿病肾病和盐相关高血压的有希望的药理学技术。然而，目前的报告往往相互矛盾或含糊不清，这使得许多人质疑肾上腺外醛固酮是否存在，或者它是否具有任何生理和病理生理意义。
