ALTERED RENAL KALLIKREIN AND RENIN GENE-EXPRESSION IN NEPHROTIC RATS AND MODULATION BY CONVERTING-ENZYME INHIBITION

Urinary kallikrein excretion (UKE) is decreased in rats with passive H eymann nephritis (PHN), but increases after converting enzyme inhibiti on (CEI). Although CEI potentiates bradykinin activity, neither the ef fect of CEI on kallikrein secretion nor the abnormal renal kallikrein metabolism in PHN has been examined previously. To determine the mecha nism by which CEI increases UKE, normal rats and PHN received enalapri l, 40 mg/kg per d orally for 4 d. UKE was 85% lower in PHN than in nor mals and increased in both groups after CEI, although UKE in PHN remai ned significantly less than in normals. Kallikrein mRNA was significan tly lower in PHN compared to normals but not in PHN treated with CEI a nd did not change in normal rats. Renin mRNA was significantly lower i n PHN, and was stimulated by CEI only in normals. Renal kallikrein and renin content were not different and were not altered by CEI. Both ka llikrein and renin genes appear to be transcriptionally suppressed in rats with PHN and the depressed kallikrein mRNA levels can be reversed by CEI. The modest increase in UKE despite normalization of kallikrei n mRNA after CEI suggests that there is also a posttranscriptional def ect in synthesis and/or secretion of kallikrein.