PARACRINE REGULATION OF THE RENIN ALDOSTERONE SYSTEM

A number of clinical states have been described where there are derangements or discrepancies between renin-angiotensin and aldosterone secretion. We have studied the potential effect of some cytokines or growth factors (peptide regulatory factors) on this system in vitro. Both tumor necrosis factor/cachectin and interleukin I are potent regulators acting as renin secretogogues and inhibitors of aldosterone synthesis. These actions are mediated by prostaglandin cyclooxygenase products and their actions mimic the syndrome of hyperreninemic hypoaldosteronism in critical illness. Insulin and insulin-like growth factor I are also renin secretogogues in vitro However in a diabetic model (streptozotocin rat), there is resistance to both agonists as well as enhanced feedback suppression to angiotensin. A third peptide, transforming growth factor (TGFbeta) has even more complex actions, acting as a secretogogue at low doses (10(-12) M) but inhibiting renin at higher doses. TGFbeta production is increased in the diabetic state so that this peptide as well as the insulin family may be involved in hyporeninemic hypoaldosteronism.