ANGIOTENSIN I-CONVERTING ENZYME-ACTIVITY IN TUBULAR FLUID ALONG THE RAT NEPHRON

The activity of angiotensin I-converting enzyme (ACE) was determined i n tubular fluid collected from several portions of the rat nephron and urine and in total and efferent arteriolar blood using hippuryl-L-His -leu as substrate. ACE activity decreased 30% from the pre- to the pos tglomerular arterioles (P < 0.001), suggesting a role of the glomerulu s in ACE clearance. The enzyme activity was found to be present throug hout the rat nephron. However, the highest activities were found in th e proximal tubule and urine (0.692 +/- 0.007 and 1.05 +/- 0.015 pmol . mu l(-1). min(-1), respectively). Compared with other segments, ACE ac tivity decreased from the initial portion of the proximal tubule to th e distal nephron and increased again in the urine. Along the proximal tubule, ACE was secreted and degraded and/or reabsorbed and then secre ted again into the collecting duct; no ACE activity was found in the l ate distal tubule, but a high level was detected in the urine, indicat ing a potential physiological role in the inactivation of the kinins f ormed by kallikrein beyond the connecting tubules. Moreover, the possi ble role of mesangial cells (MC) in the decrease of intraglomerular AC E was also evaluated. The analysis of ACE gene showed that MC in cultu re are able to express ACE mRNA. Moreover, ACE is produced as an ectoe nzyme and as a secreted form of the enzyme, indicating a potential eff ect of local angiotensin II production on MC function.