Endogenous nitric oxide formation in cardiac myocytes does not control respiration during β-adrenergic stimulation.

In the heart, endothelial nitric oxide (NO) controls oxygen consumption in the working heart through paracrine mechanisms. While cardiac myocytes contain several isoforms of NO synthases, it is unclear whether these can control respiration in an intracrine fashion. A long-standing controversy is whether a NOS exists within mitochondria. By combining fluorescence technologies with electrical field stimulation or the patch-clamp technique in beating cardiac myocytes, we identified a neuronal NO synthase (nNOS) as the most relevant source of intracellular NO during β-adrenergic stimulation, while no evidence for a mitochondria-located NOS was obtained. The amounts of NO produced by non-mitochondrial nNOS were insufficient to regulate respiration during β-adrenergic stimulation, arguing against intracrine control of respiration by NO within cardiac myocytes. Endothelial nitric oxide (NO) controls cardiac oxygen (O