On the natriuretic effect of verapamil: inhibition of ENaC and transepithelial sodium transport.
On the natriuretic effect of verapamil: inhibition of ENaC and transepithelial sodium transport.
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关于维拉帕米的利尿钠作用：抑制 ENaC 和跨上皮钠转运。
DOI：
10.1152/ajprenal.00253.2001
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Desir,GaryV
中科院分区：
文献类型：
--
作者：
Segal,AlanS;Hayslett,JohnP;Desir,GaryV
The natriuretic effect of Ca2+channel blockers has been attributed to hemodynamic changes and to poorly defined direct tubular effects. To test the possibility that verapamil may inhibit Na+reabsorption at the distal tubule, its effect on transepithelial Na+transport in aldosterone-stimulated A6 cells was determined. Cells were grown on permeable supports, and short-circuit current (Isc) measured in an Ussing chamber was used as a surrogate marker for transepithelial Na+transport. Application of 300 μM verapamil to the apical side inhibitedIscby 77% and was nearly as potent as 100 μM amiloride, which inhibitedIscby 87%. Verapamil-induced inhibition ofIscwas accompanied by a significant increase in transepithelial resistance, suggesting blockade of an apical conductance. Its action on transepithelial Na+transport does not appear to occur through inhibition of L-type Ca2+channels, sinceIscwas unaffected by removal of extracellular Ca2+. Verapamil also does not appear to inhibitIscby modulating intracellular Ca2+stores, since it fails to inhibit transepithelial Na+transport when added to the basolateral side. The effect on Na+transport is specific for verapamil, since nifedipine, Ba2+, 4-aminopyridine, and charybdotoxin do not significantly affectIsc. A direct effect of verapamil on the epithelial Na+channel (ENaC) was tested using oocytes injected with the α-, β-, and γ-subunits. We conclude that verapamil inhibits transepithelial Na+transport in A6 cells by blocking ENaC and that the natriuresis observed with administration of verapamil may be due in part to its action on ENaC.
