Aldosterone (ALDO) increases transmembrane influx of Na+ in vascular smooth muscle (VSM) cells through increased synthesis of Na+ channels.
We have previously reported our studies on glucocorticoid (GC) effects on Na+ influx in vascular smooth muscle (VSM) cells. We now report a parallel study on the effect of mineralocorticoid (MC) on Na+ influx in VSM cells. Unidirectional influx of Na+ was measured in cultured cells of rabbit aortic media with 22Na as tracer. Cells were treated with near physiologic (5 nM) or supraphysiologic (50 nM) aldosterone (ALDO) for 24 or 48 hours, or for 7 to 10 days, in the presence of competitive inhibitors of MC-receptor binding, K-prorenoate (PRN), or GC-receptor binding, RU 486. ALDO at 5 nM increased Na+ influx by 98% +/- 12%, but only after 7-10 days of treatment. This effect was inhibited by PRN, but not by RU 486, and blocked by amiloride but not by ethylisopropyl-amiloride or by dichlorobenzamil (DCB). In VSM cell membranes from aortae of rabbits treated in vivo with ALDO (2 mg/day) for 4 weeks. Na+ channels were quantified by determination of specific [3H]amiloride binding in the presence of excess of DCB and EIPA to exclude tracer binding from the Na+/Ca2+ exchanger and the Na+/H+ antiporter. ALDO doubled the number of of Na+ channels in such isolated cell membranes, as determined by Bmax per mg membrane protein. We propose that this vascular effect of ALDO may constitute an important pathogenetic mechanism of hypertension induced by chronic excess of MC, in addition to the well known renal mechanism.
Kornel
L
L
Department of Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, USA.
Smoszna-Konaszewska
B
B
D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D011869:Radioligand Assay; D011987:Receptors, Steroid / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000096:biosynthesis / Q000187:drug effects* / Q000378:metabolism
D011987:Receptors, Steroid; D015222:Sodium Channels; D000450:Aldosterone; D003907:Dexamethasone; D012964:Sodium