Aldosterone activates Na+/H+ exchange in vascular smooth muscle cells by nongenomic and genomic mechanisms

Abstract

The short-term effect of ALDO on NHE activity is not mediated through either MR or GR, occurs independent of gene transcription and protein synthesis, and occurs through a mechanism involving the structural elements of cytoskeleton. The long-term effect of ALDO on NHE activity occurs through both MR and GR and requires gene transcription and protein synthesis. Both short- and long-term effects of ALDO are mediated through PKC activation. Therefore, ALDO activates NHE by nongenomic and genomic mechanisms in VSMCs.

Rapid Effects of Aldosterone and Spironolactone in the Isolated Working Rat Heart

“…In vascular smooth muscle cells, endothelial cells, and colonic epithelial cells, aldosterone has rapidly increased intracellular calcium. 20,23,27 On the other hand, in adult rat cardiac myocytes, short-term exposure to aldosterone failed to elicit a significant effect on calcium current. 39 Aldosterone has been shown to directly enhance sodiumhydrogen antiporter activity and modulate acid-base balance in developing cardiac myocytes.…”

Nongenomic stimulation of vacuolar H + -ATPases in intercalated renal tubule cells by aldosterone

“…These involve rapid modulations of epithelial Na and K channel activity and of Na͞H exchange (40,41). Representative examples are stimulation of Na ϩ ͞H ϩ exchanger by aldosterone in colon crypt cells, the Madin-Darby canine kidney cell line, and vascular smooth muscle cells (40,42,43). Nongenomic actions have also been observed for other steroid hormones, such as glucocorticoids, progesterone, and estrogen, and for androgens and vitamin D 3 (16,27).…”

Effects of Aldosterone on the Vasculature

“…62 Both short-and long-term VSMC exposure to aldosterone increased NHE activity. Gene transcription (actinomycin D) and protein synthesis inhibitors (cycloheximide) had no effect on short-term actions but blocked long-term effects.…”