Figure 1. Downregulation of VSM K_ATP overactivity abolishes cardiac hypertrophy.

(A) Transgenic approach to generate inducible, tissue-specific, dominant-negative Cantu mice (see text). (B) Representative whole-cell recordings of K_ATP channel activity in aortic SM cells from WT (left) and SM-DN^wt/wt mouse following tamoxifen induction (right). Cells were voltage-clamped at –70 mV and currents recorded in high-Na⁺ or -K⁺ as indicated. Pinacidil (Pin) and glibenclamide (Glib) were administrated as indicated. (C) K_ATP channel current density from experiments as in C. Data for VSM cells isolated from WT (black bar), SM-DN^wt/wt without tamoxifen induction (white bar), and SM-DN^wt/wt with tamoxifen administration (gray bar). (D) BP recordings from anesthetized WT (black), SUR2^wt/AV (orange), and SM-DN^wt/AV (brown) mice. (E) Mean arterial pressure (MAP) in nontransgenic (Non TG), single-transgenic (STG), and double-transgenic (SM-DN) WT and SUR2^wt/AV mice. (F) Left: Representative images of excised hearts from WT (top), SUR2^wt/AV (middle), and SM-DN^wt/AV (bottom) mice. Right: Heart size (heart weight normalized to tibia length; HW/TL) from nontransgenic (Non TG), single-transgenic (STG), and double-transgenic (SM-DN), WT and SUR2^wt/AV mice. For all figures, individual data points are represented as open circles, bars show mean ± SEM. Statistical significance was determined by 1-way ANOVA and post hoc Tukey’s test for pairwise comparison. *P < 0.05; **P < 0.01 from pairwise post hoc Tukey’s test.