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. 2017 Dec 23;6(12):e007157. doi: 10.1161/JAHA.117.007157

Figure 2.

Figure 2

TRPV4 channel activation dilates cannulated, pressurized small PAs through endothelial nitric oxide synthase (eNOS) activation, and small MAs through IK/SK channel activation. Fourth‐order PAs from left lung were cannulated and pressurized to 15 mm Hg and third‐order MAs were pressurized to 80 mm Hg to record the changes in internal diameter. Both PAs and MAs were preconstricted with thromboxane analog U46619 (100 nmol/L). Dilation to NS309 (1 μmol/L), an activator of endothelial IK and SK channels, was used as a criterion to confirm functional viability of the endothelium. A, Representative traces for GSK101‐induced vasodilation under control conditions, in the endothelium‐denuded PAs, in the PAs from TRPV4−/− mice, in the presence of IK and SK channel inhibitors (Tram‐34 and apamin, respectively), NOS inhibitor L‐NNA, and in PAs from eNOS −/− mice. Experiments in eNOS −/− mice were performed in the presence of iNOS inhibitor 1400W to account for a possible compensation by iNOS.42 B, (left to right) Averaged diameter responses to NS309 in control (n=37 arteries) and endothelium‐denuded (n=5 arteries) PAs, GSK101 in control PAs (n=8 arteries), in endothelium‐denuded PAs (n=5 arteries), in PAs from TRPV4−/− mice (n=9 arteries), in the presence of GSK219 (n=4 arteries), Tram‐34+apamin (n=9 arteries), L‐NNA (n=11 arteries), 1400W (n=5 arteries), NPLA (nNOS inhibitor, n=8 arteries), and in PAs from eNOS −/− mice (n=5 arteries). Data are mean±SEM; P<0.05 using 2‐way ANOVA and post hoc Tukey test; *P<0.05 vs corresponding concentration under control conditions. C, Representative diameter traces for the effect of GSK101 on MA diameter in the absence (left) or presence (right) of the IK and SK channel inhibitors Tram‐34 and apamin, respectively. D, Averaged diameter data for GSK101‐induced dilations in the absence or presence of Tram‐34 and apamin (n=4 arteries; *P<0.05 using 2‐way ANOVA and post hoc Tukey test). EC indicates endothelial cell; L‐NNA, l‐N G‐nitroarginine; MAs, mesenteric arteries; NPLA, Nω‐Propyl‐L‐arginine hydrochloride ; PAs, pulmonary arteries; TRPV4, transient receptor potential vanilloid 4.