Influence of endothelin on local aldosterone production synthesized by human renal tubular cells

Abstract

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. 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. (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). 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.