Transient receptor potential canonical type 3 channels and blood pressure in humans.
OBJECTIVE
There is evidence that transient receptor potential canonical type 3 (TRPC3) cation channels are involved in the regulation of blood pressure, but this has not been studied using human renal tissue. We tested the hypothesis that the expression of TRPC3 in human renal tissue is associated with blood pressure in patients.


METHODS
TRPC3 was detected in cultured human endothelial cells and in vascular endothelium cells from human renal tissue by immunoblotting, immunohistochemistry, and quantitative real-time reverse transcriptase-PCR. The changes of TRPC3 and vascular endothelial growth factor receptor type 2 expression in cultured human endothelial cells were measured after administration of vascular endothelial growth factor isoform 121.


RESULTS
In cultured human endothelial cells, vascular endothelial growth factor isoform 121 significantly reduced TRPC3 expression by 57% and vascular endothelial growth factor receptor type 2 by 70%. This reduction was partly blocked by phosphatidylinositol 3-kinase inhibitors, wortmannin, or LY294002. Downregulation of TRPC3 channel expression was associated with reduced calcium influx. The changes of calcium influx could be abolished by the inhibitor of TRPC channels, 2-aminoethoxydiphenylborane, pointing to their functional importance. TRPC3 expression was significantly higher in patients with SBP more than 140 mmHg compared with patients with SBP of 140 mmHg or less (0.00181 +/- 0.00059 versus 0.00037 +/- 0.00012 arbitrary units; P < 0.01).


CONCLUSIONS
The data support the hypothesis that TRPC3 expression in human renal tissue including vascular endothelium is associated with blood pressure regulation in humans.
Thilo
Florian
F
Medizinsche Klinik Nephrologie, Institut für Pathologie, Charité Campus Benjamin Franklin, Berlin, Germany.
Baumunk
Daniel
D
Krause
Hans
H
Schrader
Mark
M
Miller
Kurt
K
Loddenkemper
Christoph
C
Zakrzewicz
Andreas
A
Krueger
Katharina
K
Zidek
Walter
W
Tepel
Martin
M
D001483:Base Sequence; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050052:TRPC Cation Channels / Q000235:genetics / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
D017931:DNA Primers; D012333:RNA, Messenger; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2