Recently alternative renin transcripts have been discovered lacking exon 1 and thus the signal sequence for a cotranslational transport to the endoplasmatic reticulum. The encoded protein, exon (2-9) renin, cannot be secreted and remains within the cells. Its function is unknown. In the rat outer adrenal cortex, exon (2-9) renin is imported into mitochondria and its expression increases under conditions which stimulate aldosterone production. We hypothesized that exon (2-9) renin regulates aldosterone production. To test this hypothesis we generated transgenic rats overexpressing exon (2-9) renin under control of the CXCMV promoter.

Results: Four transgenic lines were obtained expressing the transcript in various tissues including the adrenal gland. Plasma renin levels (PRC) were lower and aldosterone levels (PAC) were higher in three transgenic lines, when compared with nontransgenic controls (PAC/PRC in controls: 2.8±2.3; line 307: 1.9±0.8; n. s.; line 284: 5.8±1.9; p<0.02; line 294: 5.0±2.3; p<0.001; line 276: 10.3±5.1; p<0.001). Conclusion:

Expression of intracellular exon (2-9) renin in the adrenal gland increases aldosterone production.