Exogenous and locally synthesized angiotensin II and glomerulosa cell functions.

Abstract

We conducted this study to examine the effects of exogenous and locally synthesized angiotensin II (Ang II) on cultured bovine glomerulosa cell functions (i.e., aldosterone secretion and cell proliferation measured by [3H] thymidine incorporation into the deoxyribonucleic acids (DNA) after the arresting cell growth). The effects of Ang II were found to depend on the culture conditions. After 72 hours of serum-free culture, the differentiated function of cultured cells such as Ang II-induced aldosterone secretion was suppressed, and DNA synthesis was stimulated by Ang II. After 24 hours of serum-free culture, the cells showed a good steroidogenic response and DNA synthesis was inhibited after Ang II was added in a concentration-dependent manner (10(-11) to 10(-7) M). Ang II was detected in 24 hours of culture grown in a serum-free medium by a specific Ang II radioimmunoassay. Ion-exchange high-performance liquid chromatography indicated that this immunoreactive (ir) Ang II was composed mainly of Ang II with small amounts of angiotensin III (Ang III). The concentration of irAng II in the cultured medium was significantly reduced by the addition of captopril, indicating de novo generation and secretion of Ang II. Captopril (10(-5) to 10(-3) M) reduced aldosterone secretion and reciprocally increased DNA synthesis. Ang II antagonist, [Sar1, Ile8] Ang II, increased DNA synthesis presumably by competitive blockade of locally synthesized Ang II. In summary, Ang II inhibited cell proliferation. In addition to exogenous (circulating) Ang II, Ang II was generated and secreted by the glomerulosa cells themselves, and this locally synthesized Ang II appeared to work as an autocrine factor to stimulate aldosterone secretion and to suppress cell proliferation.