Short communication
Interleukin-1 contributes to the induction of nitric oxide synthase by endotoxin in vivo

https://doi.org/10.1016/0014-2999(93)90634-TGet rights and content

Abstract

We investigated the role of interleukin-1 in the induction of a Ca2+-independent nitric oxide (NO) synthase by bacterial endotoxin in vivo. In anaesthetized rats, pretreatment with interleukin-1 receptor antagonist (interleukin-1ra; 16 mg kg−1 i.v., followed by an infusion of 2.4 mg kg−1 h−1) ameliorated the delayed hypotension and tachycardia in response to endotoxin (2 mg kg−1 i.v.). Endotoxaemia for 3 h induced a Ca2+-inependent NO synthase activity in the lung and reduced the contractions to noradrenaline in the thoracic aorta ex vivo. Treatment with interleukin-1ra attenuated both the induction of NO synthase in the lung (by 46±5%) and the endotoxin-induced hyporeactivity to noradrenaline in the aorta. Thus, endogenous interleukin-1 contributes to the induction of NO synthase in response to endotoxin in vivo.

References (16)

There are more references available in the full text version of this article.

Cited by (85)

  • CAT-1 as a novel CAM stabilizes endothelial integrity and mediates the protective actions of l-Arg via a NO-independent mechanism

    2015, Journal of Molecular and Cellular Cardiology
    Citation Excerpt :

    The excessive NO production by iNOS in this case results in relaxation of vascular smooth muscle through raising intracellular cyclic guanosine monophosphate (cGMP) levels and then causes hypotension and vascular hyporeactivity [58]. However, NOS inhibitors were not uniformly successful in improving sepsis-induced hypotension, and inhibition of NOS only partially restores the endotoxin-induced vascular hyporeactivity [59–62]. Furthermore, based on other recent understanding of contributing factors and mechanisms of uncoupling of eNOS and increased eNOS-derived production of ROS and H2O2, the innovative therapies targeting at these mechanisms of action, such as BH4 has been repeatedly found, have failed in clinical trials despite early success in pre-clinical models [63].

  • Vasoplegia in septic shock: Do we really fight the right enemy?

    2014, Journal of Critical Care
    Citation Excerpt :

    Nitric oxide (NO) induced by a Ca2 +-independent isoform of NO synthase (iNOS) has been suggested to play an important role in activating soluble guanylyl cyclase (sGC), thus producing relaxation of vascular smooth muscle through rising in intracellular cyclic guanosine monophosphate (cGMP) levels and then causes hypotension and vascular hyporeactivity [9,10]. However, NO synthase (NOS) inhibitors were not uniformly successful in improving sepsis-induced hypotension outcome, and inhibition of NOS only partially restores the endotoxin-induced vascular hyporeactivity [11-14]. The aim of the present review is to discuss the most recent cited underlying mechanisms of decreased responsiveness to vasoconstrictors in sepsis and to briefly outline current therapeutic strategies and possible future approaches.

  • Nitric oxide in septic shock

    1999, Biochimica et Biophysica Acta - Bioenergetics
View all citing articles on Scopus
View full text