Previous experimental work has demonstrated that excessive nitric oxide (NO) is produced during sepsis and is a key mechanism for vascular dysfunction. The amount of NO produced appears to be directly related to hypotension and decreased responsiveness to vasoconstrictors. Three nitric oxide synthase (NOS) isoforms may contribute to hypotension during sepsis, but most studies suggest that the majority of NO is produced by nitric oxide synthase 2 (NOS-2). Nardi and colleagues sought to define the contribution of nitric oxide synthase 1 (NOS-1) and its relationship with the main vascular effector of NO, soluble guanylate cyclase (sGC), in an animal model of sepsis.
The investigators found that NO production by NOS-1 has an important role in sepsis-induced vascular dysfunction. Limitations of this study include the nature of the sepsis model and the fact that the NOS-1 and sGC association was established only in smooth muscle. This work may some day be clinically relevant for septic patients with refractory hypotension if the results can be replicated in humans.
Read the full Concise Critical Appraisal by logging into the SCCM eCommunity. Concise Critical Appraisal is a regular feature aimed at highlighting the best and most relevant literature from a variety of academic journals and encouraging discussion around recent studies and research.