References
Query Results -- Details
MGI Accession ID: MGI:1888828
J Number: J:64176
Other Accession IDs:
Title: Protection against TNF-induced lethal shock by soluble guanylate cyclase inhibition requires functional inducible nitric oxide synthase.
Authors: Cauwels A; Van Molle W; Janssen B; Everaerdt B; Huang P; Fiers W; Brouckaert P
Journal: Immunity
Volume: 13
Issue: 2
Date: 2000 Aug
Year: 2000
Pages: 223-31
Review Status: Peer Reviewed
Abstract:
Hypotension and shock observed in sepsis, SIRS, and tumor necrosis factor (TNF) or cytokine-based cancer treatment are the consequence of excessive nitric oxide (NO) production and subsequent soluble guanylate cyclase (sGC)-mediated vascular smooth muscle relaxation. We demonstrate here that, while NO synthase (NOS) inhibitors exacerbated toxicity, inhibitors of sGC activation protected against TNF-induced lethality, bradycardia, and hypotension. Importantly, sGC inhibition did not interfere with the antitumor activity of TNF. Using NOS inhibitors or iNOS-deficient animals, we furthermore observed that no protection against TNF toxicity could be obtained in the absence of NO. These data imply that iNOS- (and not eNOS-) derived NO is an endogenous protective molecule indispensable to survive a TNF challenge and exerting this beneficial effect via sGC-independent mechanisms.
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