G-protein mediated signaling pathways in myogenic responsiveness of mouse mesenteric artery

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Lars Jørn Jensen, Philomeena Daphne Joseph, Kristian Agmund Haanes, Susanne Syberg Hansen, Niklas Rye Jørgensen, Jakob Lerche Hansen, Max Salomonsson

Myogenic responsiveness (MR) is the ability of a small artery to constrict to an increase in intraluminal pressure and dilate to a decrease in pressure. The mechanisms linking an increase in pressure to VSMC contraction are suggested to involve mechanical activation of AT1-receptors. Our aim was to explore the role of alternative G protein-coupled receptor (GPCR) pathways. MR of pressurized mouse mesenteric arteries (MA; <200 µm) was measured as the slope of the active diameter curve. The PLC inhibitors U73122 (0.5 µM), ET-18-OCH3 (10 µM), and the PKC inhibitor BIM-X (1 µM) impaired MR. Inhibitors of PLA2 (AACOCF3, 5 µM), DAG lipase (RHC80267, 20 µM), PI3-kinase (wortmannin, 0.03 µM), CYP4A (HET0016, 10 µM), and TRPC channels (SKF96365, 10 µM) had no effects. Gq/11 and G12 mRNA and protein were expressed in MA. The Gα/q inhibitor YM-254890 (0.1 µM) and the AT1-R blocker valsartan (0.3 µM) inhibited MR. The GPCR antagonists prazosin (1 µM), losartan (0.1 µM), BQ-123 (1 µM), and SQ29548 (1 µM) had no effects. The P2Y-R antagonists suramin (100 µM) and PPADS (10 µM) inhibited MR, but the ATP diphosphatase apyrase (20 U/mL) did not. MR was similar in P2Y2-/- vs. age-matched WT mice. Preliminary data suggest a reduction of MR in P2Y6-/- mice vs. WT, and that the Rho-kinase (ROCK) inhibitor Y27632 (3 µM) inhibits MR. Thus, Gq/11 and possibly G12 pathways mediate pressure activation in mouse MA through PLC, PKC, and ROCK. MR may be initiated by mechanical activation of P2Y6-R and AT1-R in VSMCs.
Original languageEnglish
Article numberP119
JournalMicrocirculation
Volume22
Issue number7
Pages (from-to)631
Number of pages1
ISSN1073-9688
DOIs
Publication statusPublished - 2015
Event10th World Congress for Microcirculation - Kyoto International Conference Center, Kyoto, Japan
Duration: 25 Sep 201527 Sep 2015

Conference

Conference10th World Congress for Microcirculation
LocationKyoto International Conference Center
CountryJapan
CityKyoto
Period25/09/201527/09/2015

ID: 163126763