Pre-eclampsia: the Potential of GSNO Reductase Inhibitors

Abstract

Purpose of review: Pre-eclampsia remains a leading worldwide cause of maternal death and of perinatal morbidity. There remains no definitive treatment except delivery of the fetus.

Recent findings: Recent insights into the cardiovascular changes that are evident prior to, during, and persist after pre-eclampsia have improved understanding of the underlying pathophysiology-disruption of normal endothelial function and decreased nitric oxide bioavailability. S-nitrosoglutathione (GSNO) is an endogenous S-nitrosothiol that acts as a NO pool and, by replenishing or preventing the breakdown of GSNO, endothelial dysfunction can be ameliorated. GSNO reductase inhibitors are a novel class of drug that can increase NO bioavailability. GSNO reductase inhibitors have demonstrated improvement of endothelial dysfunction in animal models, and in vivo human studies have shown them to be well tolerated. GSNOR inhibitors offer a potentially promising option for the management of pre-eclampsia.

Keywords: GSNO; GSNO reductase inhibitors; Pre-eclampsia; S-nitrosoglutathione.

Fig. 1

Potential transnitrosation signaling pathways. NOS nitric oxide synthase, NO nitric oxide, GSNO S-nitrosoglutathione, GSH glutathione, GSNOR S-nitrosoglutathione reductase, CBR1 carbonyl reductase, Trx thioreduxin, TrxR thioreduxin reductase. Adapted from Smith et al. [•]. Reproduced with permission

Fig. 2

Simplified schematic of NO/S-nitrosothiol pathways and potential therapeutic targets. Reproduced from Johal et al. [34]