Effects of amiloride, benzamil, and alterations in extracellular Na+ on the rat afferent arteriole and its myogenic response

X Wang, K Takeya, P I Aaronson, K Loutzenhiser, R Loutzenhiser

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    36 Citations (Scopus)

    Abstract

    Recent studies have implicated epithelial Na+ channels ( ENaC) in myogenic signaling. The present study was undertaken to determine if ENaC and/or Na+ entry are involved in the myogenic response of the rat afferent arteriole. Myogenic responses were assessed in the in vitro hydronephrotic kidney model. ENaC expression and membrane potential responses were evaluated with afferent arterioles isolated from normal rat kidneys. Our findings do not support a role of ENaC, in that ENaC channel blockers did not reduce myogenic responses and ENaC expression could not be demonstrated in this vessel. Reducing extracellular Na+ concentration ([Na+](o); 100 mmol/l) did not attenuate myogenic responses, and amiloride had no effect on membrane potential. Benzamil, an inhibitor of ENaC that also blocks Na+/Ca2+ exchange (NCX), potentiated myogenic vasoconstriction. Benzamil and low [Na+](o) elicited vasoconstriction; however, these responses were attenuated by diltiazem and were associated with significant membrane depolarization, suggesting a contribution of mechanisms other than a reduction in NCX. Na+ repletion induced a vasodilation in pressurized afferent arterioles preequilibrated in low [Na+](o), a hallmark of NCX, and this response was reduced by 10 mu mol/l benzamil. The dilation was eliminated, however, by a combination of benzamil plus ouabain, suggesting an involvement of the electrogenic Na+-K+-ATPase. In concert, these findings refute the premise that ENaC plays a significant role in the rat afferent arteriole and instead suggest that reducing [Na+](o) and/ or Na+ entry is coupled to membrane depolarization. The mechanisms underlying these unexpected and paradoxical effects of Na+ are not resolved at the present time
    Original languageEnglish
    Pages (from-to)F272 - F282
    JournalAmerican Journal of Physiology (Renal)
    Volume295
    Issue number1
    DOIs
    Publication statusPublished - Jul 2008

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