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Am J Physiol Renal Physiol. 2008 Jan;294(1):F212-9. Epub 2007 Oct 31.

Angiotensin II-stimulated Ca2+ entry mechanisms in afferent arterioles: role of transient receptor potential canonical channels and reverse Na+/Ca2+ exchange.

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  • 1Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.


In afferent arterioles, the signaling events that lead to an increase in cytosolic Ca(2+) concentration ([Ca(2+)](i)) and initiation of vascular contraction are increasingly being delineated. We have recently studied angiotensin II (ANG II)-mediated effects on sarcoplasmic reticulum (SR) mobilization of Ca(2+) and the role of superoxide and cyclic adenosine diphosphoribose in these processes. In the current study we investigated the participation of transient receptor potential canonical channels (TRPC) and a Na(+)/Ca(2+) exchanger (NCX) in Ca(2+) entry mechanisms. Afferent arterioles, isolated with the magnetized polystyrene bead method, were loaded with fura-2 to measure [Ca(2+)](i) ratiometrically. We observed that the Ca(2+)-dependent chloride channel blocker niflumic acid (10 and 50 microM) affects neither the peak nor plateau [Ca(2+)](i) response to ANG II. Arterioles were pretreated with ryanodine (100 microM) and TMB-8 to block SR mobilization via the ryanodine receptor and inositol trisphosphate receptor, respectively. The peak [Ca(2+)](i) response to ANG II was reduced by 40%. Addition of 2-aminoethoxydiphenyl borane to block TRPC-mediated Ca(2+) entry inhibited the peak [Ca(2+)](i) ANG II response by 80% and the plateau by 74%. Flufenamic acid (FFA; 50 microM), which stimulates TRPC6, caused a sustained increase of [Ca(2+)](i) of 146 nM. This response was unaffected by diltiazem or nifedipine. KB-R7943 (at the low concentration of 10 microM) inhibits reverse (but not forward) mode NCX. KB-R7943 decreased the peak [Ca(2+)](i) response to ANG II by 48% and to FFA by 38%. We conclude that TRPC6 and reverse-mode NCX may be important Ca(2+) entry pathways in afferent arterioles.

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