Physiologic resistance to the action of aldosterone

The collecting duct is one of the major targets for aldosterone's action. Experiments conducted several years ago suggested that the major site of action on Na+ and K+ transport was the cortical portion, the cortical collecting duct (CCD). Subsequent studies have shown that the entire collecting duct is capable of responding to aldosterone, but does so differently according to the region. The inner medullary collecting duct (IMCD), while exhibiting a relatively low rate of Na+ transport in isolated, perfused tubules, can develop substantial rates of Na+ transport when put in primary culture. The IMCD, in contrast to the CCD, usually secretes little K+. Investigations into the mechanisms for the lower rates of Na+ transport have revealed that transforming growth factor-beta (TGF-beta), which is endogenously produced in the inner medulla, can markedly reduce the natriferric action of aldosterone. 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. The mechanism of this antagonism appears to involve pathways that are parallel and independent of the major transcriptional effects of aldosterone.