Lack of NOS3 ameliorates cardiac hypertrophy and dilatory remodeling in response to TAC-induced pressure overload. (A) Formalin-fixed (10%) hearts showing progressive cardiac hypertrophy with marked dilatory remodeling in WT TAC mice versus more modest and concentric cardiac hypertrophy at 3 weeks, with minimal further progression at 9 weeks, in NOS3^–/– TAC mice. Scale bar: 10 mm. (B) Mean data for HW/TL ratio (n = 6 or more per group). (C) Histological analysis of WT and NOS3^–/– TAC hearts. PAS methenamine staining reveals increased interstitial fibrosis (dark stain, upper right panel) and myocyte size in WT TAC hearts. NOS3^–/– TAC hearts reveal minimal fibrosis and blunted increase in myocyte size. Scale bar: 100 μm. (D) Summary quantification of cardiomyocyte diameter (n = 4–5 per genotype, 6–10 regions per heart, 50–60 cells per heart for size estimates). P values shown indicate the effect of genotype on the TAC-stimulated response (2–way ANOVA).