Rapid actions of aldosterone: lymphocytes, vascular smooth muscle and endothelial cells

The genomic theory of steroid action has been the unquestioned dogma for th e explanation of steroid effects over the past four decades. Despite early observations on rapid steroid effects being clearly incompatible with this theory, only recently has nongenomic steroid action been recognized more wi dely and led to a critical reappraisal of unsolved questions about this dog ma. Evidence for nongenomic steroid effects come from all fields of steroid research now, and mechanisms of agonist action are studied with regard to membrane receptors and second messengers involved. A prominent example of a receptor/effector-cascade for nongenomic steroid effects has been describe d for rapid aldosterone effects in various cell types, including lymphocyte s, cultured vascular smooth muscle, and endothelial cells involving nonclas sical membrane receptors with a high affinity for aldosterone, but not for cortisol, and phosphoinositide turnover. As another important second messen ger, [Ca2+](i) is consistently increased by aldosterone within 1-2 min. In vascular smooth muscle cells, calcium is released from perinuclear stores, while in endothelial cells a predominant increase of subplasmalemmal calciu m is seen. Effects are half maximal at physiological concentrations of free aldosterone (0.1 nmol/L), while cortisol is inactive up to 0.1 mu mol/L; t he classical mineralocorticoid antagonist canrenone is ineffective in block ing the action of aldosterone. The data show that intracellular signaling f or nongenomic aldosterone effects also involves calcium, but pathways of ce ll activation may vary between different cell types. Future research will h ave to target the cloning of the first membrane receptor for steroids, and the evaluation of the clinical relevance of these rapid steroid effects. (C ) 1999 Elsevier Science Inc. All rights reserved.