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Role of TRPV4 channels in agonist‐induced endothelial Ca2+ entry and vasodilation: Evidence from TRPV4‐deficient mice
Author(s) -
Mendoza Suelhem A.,
Gutterman David D.,
Bubolz Aaron,
Suzuki Makoto,
Zhang David X.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1181.4
Subject(s) - trpv , myograph , chemistry , trpv4 , agonist , transient receptor potential channel , vasodilation , endocrinology , medicine , ruthenium red , acetylcholine , biophysics , pharmacology , calcium , biochemistry , trpv1 , receptor , biology , organic chemistry
Transient receptor potential vallinoid 4 (TRPV‐4), is a Ca 2+ ‐permeant cation channel implicated in endothelial‐dependent vasorelaxation to mechanical stimuli but limited information exists for agonist‐induced responses. We hypothesized that TRPV‐4 is required for agonist‐induced vasodilation by regulating Ca 2+ entry. Isometric tension was measured in isolated mesenteric arteries (MA) from wild type (WT) and TRPV‐4 knockout mice using a wire myograph. Dilation to acetylcholine (Ach, 10 −9 –10 −5 M) was diminished in TRPV‐4 −/− vs. WT MA (% max relaxation, 44±12 and 86±5, respectively n=4, P<0.05). L‐NAME, blocked Ach relaxation in TRPV‐4 −/− and WT MA (11±4 and 35±11, respectively n=4, P<0.05). Responses to papaverine were similar in WT and TRPV‐4 −/− MA. Intracellular calcium ([Ca 2+ ] i ) was assessed after intraluminal fura‐2 (fluorescence) in MA. Ach (10 −5 M) increased endothelial [Ca 2+ ] i in WT and TRPV‐4 −/− MA (Δ[Ca 2+ ] i , 49±4.6nM and 26±2.1nM, respectively n=4). The addition of 4α‐PDD, a TRPV4 opener, increased [Ca 2+ ] i in WT but not in TRPV‐4 −/− (Δ[Ca 2+ ] i , 164±30nM and 15±1.3nM, respectively n=4). In endothelium of WT MA the increase in [Ca 2+ ] was abolished by the TRPV‐4 blocker ruthenium red (Δ[Ca 2+ ] i , RR, 19±1.2nM n=4). These data suggest an important role for the TRPV‐4 channels in vasodilation to Ach, and regulation of endothelial intracellular Ca 2+ in mice MA.