Fig. 3.
β-Adrenergic inotropic response is blunted in GSNOR−/− mice. (A) Dose–response curve for the in vivo effect of ISO on cardiac contractility in WT (n = 12) and GSNOR−/− (n = 11) mice. *P < 0.05, two-way ANOVA. (B) Representative traces of sarcomere shortening and [Ca2+]i in myocytes isolated from WT and GSNOR−/− hearts at baseline and after ISO (100 nM). (C and D) [Ca2+]i and sarcomere shortening dose–response to ISO in isolated myocytes. GSNOR−/− myocytes (n = 11–13, 2–10 cells per heart) displayed a blunted response to ISO vs. WT (*P < 0.05, **P < 0.01, ***P < 0.001; n = 11–14, 2–4 cells per heart). (E and F) Specific inhibition of NOS1 with l-VNIO (100 μM) as well as pan-NOS inhibition with l-NMMA (100 μM) normalized the β-adrenergic responses in GSNOR−/− myocytes (†P < 0.05 vs. control). (G and H) Evaluation of the force–frequency response (sarcomere shortening and the amplitude of the [Ca2+]i) in isolated myocytes stimulated at 1–8 Hz. The force–frequency relationship is preserved in GSNOR−/− cardiomyocytes.