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Angiotensin II-stimulated Ca2+ entry mechanisms in afferent arterioles: role of transient receptor potential canonical channels and reverse Na+/Ca2+ exchange
- Source :
- American journal of physiology. Renal physiology. 294(1)
- Publication Year :
- 2007
-
Abstract
- In afferent arterioles, the signaling events that lead to an increase in cytosolic Ca2+ concentration ([Ca2+]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 Ca2+ 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+/Ca2+ exchanger (NCX) in Ca2+ entry mechanisms. Afferent arterioles, isolated with the magnetized polystyrene bead method, were loaded with fura-2 to measure [Ca2+]i ratiometrically. We observed that the Ca2+-dependent chloride channel blocker niflumic acid (10 and 50 μ M) affects neither the peak nor plateau [Ca2+]i response to ANG II. Arterioles were pretreated with ryanodine (100 μM) and TMB-8 to block SR mobilization via the ryanodine receptor and inositol trisphosphate receptor, respectively. The peak [Ca2+]i response to ANG II was reduced by 40%. Addition of 2-aminoethoxydiphenyl borane to block TRPC-mediated Ca2+ entry inhibited the peak [Ca2+]i ANG II response by 80% and the plateau by 74%. Flufenamic acid (FFA; 50 μM), which stimulates TRPC6, caused a sustained increase of [Ca2+]i of 146 nM. This response was unaffected by diltiazem or nifedipine. KB-R7943 (at the low concentration of 10 μM) inhibits reverse (but not forward) mode NCX. KB-R7943 decreased the peak [Ca2+]i response to ANG II by 48% and to FFA by 38%. We conclude that TRPC6 and reverse-mode NCX may be important Ca2+ entry pathways in afferent arterioles.
- Subjects :
- Male
medicine.medical_specialty
Afferent arterioles
Physiology
Anti-Inflammatory Agents
chemistry.chemical_element
Calcium
Kidney
Muscle, Smooth, Vascular
Sodium-Calcium Exchanger
Microcirculation
Rats, Sprague-Dawley
Transient receptor potential channel
Arteriole
medicine.artery
Internal medicine
Renin–angiotensin system
medicine
Animals
TRPC Cation Channels
Chemistry
Ryanodine
Angiotensin II
Thiourea
Niflumic Acid
Flufenamic Acid
Rats
Cytosol
Arterioles
Endocrinology
medicine.anatomical_structure
Biophysics
Subjects
Details
- ISSN :
- 1931857X
- Volume :
- 294
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Renal physiology
- Accession number :
- edsair.doi.dedup.....ffa5560268c780180057d2df77587189