Figure 3.

Hypercholesterolemia‐induced reduction of flow‐induced vasodilation (FIV) in inwardly rectifying K⁺ (Kir)–deficient mouse mesenteric arteries. A, Representative traces showing dilations to increasing intraluminal flow in arteries isolated from wild‐type (WT), apolipoprotein E–deficient (Apoe ^−/−), and Kir2.1 ^+/− /Apoe ^−/− mice. Arterial diameter was continuously monitored and a measurement was recorded every 30 seconds. Endothelin 1 (ET‐1) (1.2–2×10⁻¹⁰ mol/L) was used to preconstrict the vessels before an FIV protocol. At the end of an FIV protocol, papaverine (10⁻⁴ mol/L) was used to determine endothelium‐independent function and validity of the previous FIV protocol. In most cases, papaverine induced dilations >95%. B, Group data showing the full dose response to flow using the pressure gradient method in each model. For WT, 6 arteries from 4 mice; Apoe ^−/−, 4 arteries from 4 mice; and Kir2.1 ^+/− /Apoe ^−/−, 4 arteries from 4 mice. SEM was calculated using the number of mice. Inhibitors of Kir (Ba²⁺; 3×10⁻⁵ mol/L) and small conductance Ca²⁺‐activated K⁺ (apamin; 2×10⁻⁸ mol/L) channels reveal the contribution of Kir channels in (C) Apoe ^−/− and (D) Kir2.1 ^+/− /Apoe ^−/− mice is abolished while the function of small conductance Ca²⁺‐activated K⁺ remains intact in response to intraluminal flow. E, Group data highlighting differences in response to Δ100 cm H₂O determined by Bonferroni correction after 2‐way repeated measures ANOVA. *P<0.05 vs control (no inhibitor) and ^‡ P<0.05 vs Ba²⁺.