Key result
In human adrenocortical NCI-H295 cells, 3.5 mmol/L K+ stimulated angiotensin I and II formation and increased aldosterone release 3.0-fold, an effect partially decreased by ACE inhibitors and losartan.
NCI-H295 cells express most components of the renin-angiotensin system and can produce angiotensin II independently of ACE, which partially mediates K+-induced aldosterone secretion.
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NCI-H295 cells may model local adrenal RAS; leaves open translation to human hypertension physiology.
NCI-H295, a human adrenocarcinoma cell line, has been proposed as a model system to define the role of the renin-angiotensin system in the regulation of aldosterone production in humans. Because the precise cellular localization of the components of the renin-angiotensin system in human adrenal cortical cells remains unclear, we investigated their localization in this defined cell system. NCI-H295 cells expressed both angiotensinogen and renin as shown by reverse transcriptase polymerase chain reaction and immunohistochemistry. Human angiotensin-converting enzyme (ACE) was not detectable by immunocytochemistry, ACE binding, or reverse transcriptase polymerase chain reaction. However, 3.5 mmol/L K+ stimulated the formation of both angiotensin I and angiotensin II 1. 9- and 2.5-fold, respectively, and increased aldosterone release 3. 0-fold. The K+-induced stimulation of aldosterone release was decreased by captopril and enalaprilat (24% and 26%, respectively) and by the angiotensin type 1 (AT1)-receptor antagonist losartan (28%). Angiotensin II-induced stimulation of aldosterone release was abolished by losartan treatment. Specific [125I]Sar1-angiotensin II binding was detected by receptor autoradiography. The binding of [125I]Sar1-angiotensin II was completely displaced by the AT1 antagonist losartan but not by the AT2 receptor ligand PD 123319, confirming the expression of angiotensin II AT1 receptors in NCI-H295 cells. Our results demonstrate that NCI-H295 cells express most of the components of the renin-angiotensin system. Our failure to detect ACE, however, suggests that the production of angiotensin II in NCI-H295 cells may be ACE independent. NCI-H295 cells are able to produce angiotensin II, and K+ increases aldosterone secretion in part through an angiotensin-mediated pathway. The production of angiotensin II in NCI-H295 cells demonstrates that this human cell line can be useful to characterize the role of locally produced angiotensin II in the regulation of aldosterone release.
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Hilbers et al. (1999) studied this question. Potassium (K+) was evaluated on Aldosterone release and angiotensin formation. In human adrenocortical NCI-H295 cells, 3.5 mmol/L K+ stimulated angiotensin I and II formation and increased aldosterone release 3.0-fold, an effect partially decreased by ACE inhibitors and losartan.
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