[Effects of pravastatin on the expression of endothelin induced by aldosterone in rat cardiac fibroblasts].

Aim: To investigate the effects of pravastatin on endothelin(ET) expression induced by aldosterone in cultured neonatal rat cardiac fibroblasts.

Methods: ET concentration in conditioned medium was measured by radioimmunoassay, intracellular ET-1 level was evaluated by flow cytometry, and the expression of preproendothelin-1 (ppET-1) was detected and quantified using reverse transcriptase-polymerase chain reaction (RT-PCR) method.

Results: The cardiac fibroblasts, treated with aldosterone at 107 mol/L, significantly up-regulated ppET-1 mRNA expression, as well as ET-1 synthesis and release. Pravastatin (10(-5), 10(-4), 10(-3) mol/L) dose-dependently blocked these effects. In contrast, pravastatin-induced inhibitory effects were reversed in the presence of mevalonate.

Conclusion: Pravastatin down-regulated ppET-1 mRNA expression, as well as ET-1 synthesis and release induced by aldosterone in a process specifically related to mevalonate in cardiac fibroblasts.