No apparent role for T-type Ca2+ channels in renal autoregulation
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No apparent role for T-type Ca2+ channels in renal autoregulation. / Frandsen, Rasmus Hassing; Salomonsson, Max; Hansen, Pernille B. Lærkegaard; Jensen, Lars Jørn; Braunstein, Thomas Hartig; von Holstein-Rathlou, Niels-Henrik; Sørensen, Charlotte Mehlin.
I: Pflügers Archiv - European Journal of Physiology, Bind 468, Nr. 4, 2016, s. 541-550.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - No apparent role for T-type Ca2+ channels in renal autoregulation
AU - Frandsen, Rasmus Hassing
AU - Salomonsson, Max
AU - Hansen, Pernille B. Lærkegaard
AU - Jensen, Lars Jørn
AU - Braunstein, Thomas Hartig
AU - von Holstein-Rathlou, Niels-Henrik
AU - Sørensen, Charlotte Mehlin
PY - 2016
Y1 - 2016
N2 - Renal autoregulation protects glomerular capillariesagainst increases in renal perfusion pressure (RPP). Inthe mesentery, both L- and T-type calcium channels are involvedin autoregulation. L-type calcium channels participatein renal autoregulation, but the role of T-type channels is notfully elucidated due to lack of selective pharmacological inhibitors.The role of T- and L-type calcium channels in theresponse to acute increases in RPP in T-type channel knockoutmice (CaV3.1) and normo- and hypertensive rats was examined.Changes in afferent arteriolar diameter in the kidneysfrom wild-type and CaV3.1 knockout mice were assessed.Autoregulation of renal blood flow was examined duringacute increases in RPP in normo- and hypertensive rats underpharmacological blockade of T- and L-type calcium channelsusing mibefradil (0.1 μM) and nifedipine (1 μM). In contrastto the results from previous pharmacological studies, geneticdeletion of T-type channels CaV3.1 did not affect renal autoregulation.Pharmacological blockade of T-type channelsusing concentrations of mibefradil which specifically blocksT-type channels also had no effect in wild-type or knockoutmice. Blockade of L-type channels significantly attenuatedrenal autoregulation in both strains. These findings are supported by in vivo studies where blockade of T-type channelshad no effect on changes in the renal vascular resistanceafter acute increases in RPP in normo- and hypertensive rats.These findings show that genetic deletion of T-type channelsCaV3.1 or treatment with low concentrations of mibefradildoes not affect renal autoregulation. Thus, T-type calciumchannels are not involved in renal autoregulation in responseto acute increases in RPP.
AB - Renal autoregulation protects glomerular capillariesagainst increases in renal perfusion pressure (RPP). Inthe mesentery, both L- and T-type calcium channels are involvedin autoregulation. L-type calcium channels participatein renal autoregulation, but the role of T-type channels is notfully elucidated due to lack of selective pharmacological inhibitors.The role of T- and L-type calcium channels in theresponse to acute increases in RPP in T-type channel knockoutmice (CaV3.1) and normo- and hypertensive rats was examined.Changes in afferent arteriolar diameter in the kidneysfrom wild-type and CaV3.1 knockout mice were assessed.Autoregulation of renal blood flow was examined duringacute increases in RPP in normo- and hypertensive rats underpharmacological blockade of T- and L-type calcium channelsusing mibefradil (0.1 μM) and nifedipine (1 μM). In contrastto the results from previous pharmacological studies, geneticdeletion of T-type channels CaV3.1 did not affect renal autoregulation.Pharmacological blockade of T-type channelsusing concentrations of mibefradil which specifically blocksT-type channels also had no effect in wild-type or knockoutmice. Blockade of L-type channels significantly attenuatedrenal autoregulation in both strains. These findings are supported by in vivo studies where blockade of T-type channelshad no effect on changes in the renal vascular resistanceafter acute increases in RPP in normo- and hypertensive rats.These findings show that genetic deletion of T-type channelsCaV3.1 or treatment with low concentrations of mibefradildoes not affect renal autoregulation. Thus, T-type calciumchannels are not involved in renal autoregulation in responseto acute increases in RPP.
KW - Faculty of Health and Medical Sciences
KW - renal blood flow
KW - Autoregulation
KW - Calcium channel
KW - Renal vascular resistance
U2 - 10.1007/s00424-015-1770-9
DO - 10.1007/s00424-015-1770-9
M3 - Journal article
C2 - 26658945
VL - 468
SP - 541
EP - 550
JO - Pflügers Archiv - European Journal of Physiology
JF - Pflügers Archiv - European Journal of Physiology
SN - 0031-6768
IS - 4
ER -
ID: 153732711