ALDOSTERONE (ALDO) INCREASES TRANSMEMBRANE INFLUX OF NA-MUSCLE (VSM) CELLS THROUGH INCREASED SYNTHESIS OF NA+ CHANNELS( IN VASCULAR SMOOTH)

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 i n VSM cells. Unidirectional influx of Na+ was measured in cultured cel ls of rabbit aortic media with Na-22 as tracer. Cells were treated wit h near physiologic (5 nM) or supraphysiologic (50 nM) aldosterone (ALD O) for 24 or 48 hours, or for 7 to 10 days, in the presence of competi tive inhibitors of MC-receptor binding, K-prorenoate (PRN), or GC-rece ptor 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 ethylisopr opyl-amiloride or by dichlorobenzamil (DCB). In VSM cell membranes fro m aortae of rabbits treated in vivo with ALDO (2 mg/day) for 4 weeks, Na-+ channels were quantified by determination of specific [H-3]amilor ide binding in the presence of excess of DCB and EIPA to exclude trace r 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 B-max per mg membrane protein. We propose that this vascular effect of ALDO may constitute an important pathogenetic mecha nism of hypertension induced by chronic excess of MC, in addition to t he well known renal mechanism.