NOS-1-derived NO is an essential triggering signal for the development of systemic inflammatory responses

► Sepsis and endotoxemia induces organ damage and cardiovascular dysfunction. ► Early pharmacological inhibition of NOS-1 greatly improves these conditions. ► NOS-1 gene knockout reduced mortality by endotoxemia. ► A short initial pulse of NO is critical for the onset of these changes. ► NOS-1-derived NO is a key signaling factor in the initiation of systemic inflammation.