U. Hilbers et al., Local renin-angiotensin system is involved in K+-induced aldosterone secretion from human adrenocortical NCI-H295 cells, HYPERTENSIO, 33(4), 1999, pp. 1025-1030
Citations number
35
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
NCI-H295, a human adrenocarcinoma cell line, has been proposed as a model s
ystem to define the role of the renin-angiotensin system in the regulation
of aldosterone production in humans. Because the precise cellular localizat
ion of the components of the renin-angiotensin system in human adrenal cort
ical cells remains unclear, we investigated their localization in this defi
ned cell system. NCI-H295 cells expressed both angiotensinogen and renin as
shown by reverse transcriptase polymerase chain reaction and immunohistoch
emistry. Human angiotensin-converting enzyme (ACE) was not detectable by im
munocytochemistry, ACE binding, or reverse transcriptase polymerase chain r
eaction. However, 3.5 mmol/L K+ stimulated the formation of both angiotensi
n I and angiotensin II 1.9- and 2.5-fold, respectively, and increased aldos
terone 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 (AT(1))-receptor antagonist losartan (28%). Angio
tensin II-induced stimulation of aldosterone release was abolished by losar
tan treatment. Specific [I-125]Sar1-angiotensin II binding was detected by
receptor autoradiography. The binding of [I-125]Sar(1)-angiotensin II was c
ompletely displaced by the AT(1) antagonist losartan but not by the AT(2) r
eceptor ligand PD 123319, confirming the expression of angiotensin II AT(1)
receptors in NCI-H295 cells. Our results demonstrate that NCI-H295 cells e
xpress most of the components of the renin-angiotensin system. Our failure
to detect ACE, however, suggests that the production of angiotensin II in N
CI-H295 cells may be ACE independent. NCI-H295 cells are able to produce an
giotensin II, and K+ increases aldosterone secretion in part through an ang
iotensin-mediated pathway. The production of angiotensin II in NCI-H295 cel
ls demonstrates that this human cell line can be useful to characterize the
role of locally produced angiotensin II in the regulation of aldosterone r
elease.