Physiologic resistance to the action of aldosterone

The collecting duct is one of the major targets for aldosterone's action. E xperiments conducted several years ago suggested that the major site of act ion on Na+ and K+ transport was the cortical portion, the cortical collecti ng duct (CCD). Subsequent studies have shown that the entire collecting duc t is capable of responding to aldosterone, but does so differently accordin g to the region. The inner medullary collecting duct (IMCD), while exhibiti ng a relatively low rate of Na+ transport in isolated, perfused tubules, ca n develop substantial rates of Na+ transport when put in primary culture. T he IMCD, in contrast to the CCD, usually secretes little K+. Investigations into the mechanisms for the lower rates of Na+ transport have revealed tha t transforming growth factor-beta (TGF-beta), which is endogenously produce d in the inner medulla, can markedly reduce the natriferric action of aldos terone. This action of TGF-beta is not apparent within the first few hours of exposure, but its effects, even after removal, last for over 48 hours. T he mechanism of this antagonism appears to involve pathways that are parall el and independent of the major transcriptional effects of aldosterone.