Is Inhibition of Nitric Oxide Synthase an Appropriate Therapeutic Target in Sepsis?
Profound unresponsive hypotension characterized by low vascular resistance and which is refractory to vasopressors is one of the cardinal features of established septic shock. In 1987, Moncada et al, and independently, Ignarro et al reported the endothelium derived relaxing factor was indistinguishable from the free radical NO, a finding which has prompted an extraordinary outpouring of investigation into fields as diverse as vascular biology, endocrinology and neuroscience (for review see ). Vasodilation is one of the key properties of NO, and from an early stage it has been apparent that NO may play a role in the hypotension of sepsis. If that were true, then it may offer a novel therapeutic target for clinicians faced with a septic patient with refractory hypotension. The principal purpose of this chapter is to consider the evidence implicating NO in the clinical setting of sepsis; however it is necessary first to review briefly the experimental data which underpin the hypothesis.
KeywordsNitric Oxide Septic Shock Methylene Blue Septic Patient Systemic Vascular Resistance
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- 11.Billiar TR, Curran RD, Harbrecht BG, Stuehr DJ, Demetris AJ, Simmons RL (1990) Modulation of nitrogen oxide synthesis in vivo: N°-monomethyl-L-arginine inhibits endotoxin-induced nitrite/nitrate biosynthesis while promoting hepatic damage. J Leuk Biol 48: 565–569Google Scholar
- 16.Evans TE, Carpenter A, Silva AT, Cohen J (1994) Inhibition of nitric oxide synthase in experimental Gram negative sepsis. J Infect Dis (In press)Google Scholar
- 25.Geroulanos S, Schilling J, Cakmakci M, Jung HH, Largiader F (1992) Inhibition of NO synthesis in septic shock. Lancet 339: 434–435Google Scholar
- 27.Schneider F, Lutun P, Runge I, Couchot A, Tempe JD (1992) Effects of soluble guanylyl cyclase inhibition by methylene blue on the loss of vascular responsiveness to norepinephrine in human beings with either gram-negative or gram-positive septic shock. Clin Intensive Care 3 (Suppl): 11 (Abst)Google Scholar
- 28.Vallance P, Petros A, Lamb G, Leone A, Bennett D (1993) Hemodynamic, biochemical and hematological effects of a nitric oxide synthase inhibitor in patients with septic shock: A randomized study. Endothelium 1 (Suppl): s15 (Abst)Google Scholar