[Influence of endothelin on local aldosterone production synthesized by human renal tubular cells].
OBJECTIVE
To observe whether local aldosterone (ALDO) may be synthesized by human renal proximal tubular cell lines (HKC) and investigate whether endothelin-1 (ET-1) has effects on the production of local ALDO.


METHODS
The following tests were performed: (1) stimulative tests: after the HKC cells were incubated with ET-1 in different concentration (0, 10(-11), 10(-9), 10(-7) mol/L) or for different time (0, 6, 12, 24, 48 h), the levels of ALDO and angiotensin II (AngII) in the media were measured by radioimmunoassay. (2) inhibitive test: after the HKC cells were incubated with different concentration of angiotensin converting enzyme inhibitor (ACEI) (0, 10(-11), 10(-9), 10(-7), 10(-5) mol/L) and ET-1 (10(-7) mol/L), or incubated with ACEI (10(-5) mol/L) and ET-1 (10(-7) mol/L) for different time (0, 6, 12, 24, 48 h), the levels of ALDO and AngII in the media were detected by radioimmunoassay.


RESULTS
(1) Both ALDO and AngII at a basic quantity were produced by HKC cells without any stimulants. After stimulation with ET-1, the production of ALDO and AngII was increased with a dose and time dependent manner. When the HKC cells were incubated with 10(-9) and 10(-7) mol/L ET-1 for 48 h, the levels of ALDO and AngII were significantly higher than those with 0 mol/L ET-1 (P < 0.05 or P < 0.01). When the HKC cells were incubated with 10(-7) mol/L ET-1 in different time, the levels of ALDO and AngII in 12, 24 and 48 h were significantly higher than those in 0 h (P < 0.05 or P < 0.01). (2) when the HKC cells were incubated with 10(-7) mol/L ET-1 and ACEI in different concentration for 48 h, the production of AngII and ALDO was significantly decreased in 10(-9), 10(-7) and 10(-5) mol/L ACEI (vs 0 mol/L ACEI, P < 0.01). Although the AngII production was completely blocked by these concentration of ACEI (vs the basic quantity of AngII, P > 0.05), the ALDO production was not (vs the basic quantity of ALDO, P < 0.05). When the HKC cells were incubated with 10(-7) mol/L ET-1 and 10(-5) mol/L ACEI for different time, the production of AngII and ALDO was completely blocked in 6 h and 12 h (vs 0 h, P > 0.05). Although the AngII production was still completely blocked in 24 h and 48 h (vs 0 h, P > 0.05), the ALDO production was not (vs 0 h, P < 0.05).


CONCLUSIONS
Local aldosterone can be synthesized by human renal proximal tubular cells. Its production can be up-regulated by ET-1. This effect is partially mediated by AngII.
Luo
Yang
Y
Center of Nephrology, China-Japan Friendship hospital, Beijing 100029, China.
Chen
Yi-Pu
YP
D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000096:biosynthesis; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D004727:Endothelium / Q000378:metabolism*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*
D019332:Endothelin-1; D000804:Angiotensin II; D000450:Aldosterone