PRODUCTION OF ANGIOTENSINOGEN AND RENIN-LIKE ACTIVITY BY RABBIT PROXIMAL TUBULAR CELLS IN CULTURE

Recent studies suggest the presence of local angiotensin generating system in the kidney. By using in situ hybridization technique, mRNA for angiotensinogen has been shown to be present in the proximal tubule. In the present study, we have attempted to examine the production of angiotensinogen and renin-like activity by the proximal convoluted (PCT) and straight (PST) tubular cells. PCT and PST cells were obtained from microdissected rabbit proximal tubules and cultured in vitro. Angiotensinogen and renin-like activity were quantitated in culture media and cell lysates. It was found that PCT culture medium contained both angiotensinogen and renin-like activity, whereas only angiotensinogen was detected in PST culture medium. Support for de novo synthesis is provided by the observation that both angiotensinogen and renin-like activity in PCT culture medium increased in a time-dependent and hormone-sensitive manner in defined serum-free medium. These results thus demonstrate the actual production of angiotensinogen and renin-like activity by proximal tubular cells, and indicate that these locally synthesized components may contribute to the regulation of angiotensin generation in renal proximal tubule.