Figure 3.

CCh does not activate guanylyl cyclase in eNOS^null myocytes. (A) CCh significantly increased cGMP levels in ventricular myocyte primary isolates from WT but not in myocytes from eNOS^null mice. The increase in cGMP production induced by CCh in WT myocytes could be prevented by the NOS inhibitor L-nitroarginine (L-NNA) (100 μM). The NO donor SIN-1 (100 μM), increased cGMP levels to a similar extent in both WT and eNOS^null myocytes. (B) The CCh-stimulated increase in cGMP production in ventricular muscle slices was caused by the activation of a NO-dependent guanylyl cyclase. The guanylyl cyclase inhibitor 1H-[1,2,4]Oxadiazole-[4,3-a] quinoxalin-1-one (1 μM) blocked CCh-induced cGMP elevation in ventricular muscle from WT mice. The NO donor SIN-1 (100 μM) again increased cGMP levels in both WT and eNOS^null ventricular slices.