PMID- 7535648
OWN - NLM
STAT- MEDLINE
DCOM- 19950509
LR  - 20131121
IS  - 1063-7389 (Print)
IS  - 1063-7389 (Linking)
VI  - 3
IP  - 1
DP  - 1995 Feb
TI  - Alterations in nitric oxide production in various forms of circulatory shock.
PG  - 2-32
AB  - The free radical nitric oxide (NO.) is synthesized from the guanidino group of 
      L-arginine by a family of enzymes termed NO. synthase (NOS). In the earlier 
      phases of shock, activation of the endothelial, constitutive NOS (ecNOS) occurs, 
      which, in the case of endotoxic shock, is triggered by endotoxin-induced, acute 
      release of platelet-activating factor (PAF) and also other potential mediators. 
      This early overproduction of NO. results in reduced contractile responsiveness to 
      norepinephrine and contributes to the acute decrease in blood pressure afforded 
      by endotoxin. In the delayed phase of endotoxic shock, a distinct isoform of NOS 
      (iNOS) is induced in various organs and in the vessel wall. The induction of iNOS 
      is mediated by the release of endogenous tumor necrosis factor-alpha (TNF-alpha), 
      interleukin-1 (IL-1), and PAF by endotoxin. These mediators, in turn, act in 
      parallel, or in synergy to induce iNOS. Induction of iNOS contributes to delayed 
      vascular hyporeactivity in vivo and ex vivo, and to the delayed decrease in blood 
      pressure in rats with endotoxic shock. As endotoxic shock, hemorrhagic shock also 
      leads to an early activation of ecNOS, which is responsible for the early 
      vascular hyporeactivity, and a delayed induction of iNOS that contributes to 
      delayed circulatory failure (vascular decompensation and hyporeactivity). The 
      induction of iNOS in hemorrhagic shock is unlikely to be mediated by endogenous 
      release of endotoxin, e.g., due to intestinal ischemia. Endogenous circulating 
      glucocorticoids exert a tonic suppression of the induction of iNOS, as well as 
      the cardiovascular failure in response to endotoxin. Endotoxin tolerance is 
      associated with increased plasma levels of glucocorticoids, which may account for 
      the blunted cardiovascular response and reduced induction of iNOS in these 
      animals. A wide variety of drugs that exert protective effects in various models 
      of circulatory shock also inhibit the induction of iNOS, and this effect is 
      likely to contribute to their protective actions. These drugs include 
      glucocorticoids, TNF-alpha antibodies, IL-1 receptor blockers/antibodies, PAF 
      antagonists, dihydropyridine calcium-channel antagonists, tyrosine kinase 
      inhibitors, and the experimental drug cloricromene. Various forms of shock can 
      also lead to an inhibition of NO. production by the calcium-dependent 
      ecNOS.(ABSTRACT TRUNCATED AT 400 WORDS)
FAU - Szabo, C
AU  - Szabo C
AD  - Division of Critical Care, Children's Hospital Medical Center, Cincinnati, OH 
      45229, USA.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - New Horiz
JT  - New horizons (Baltimore, Md.)
JID - 9416195
RN  - 0 (Glucocorticoids)
RN  - 0 (Interleukin-1)
RN  - 0 (Platelet Activating Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.4.- (Amino Acid Oxidoreductases)
SB  - IM
MH  - Amino Acid Oxidoreductases/metabolism
MH  - Animals
MH  - Enzyme Activation
MH  - Enzyme Induction/drug effects
MH  - Glucocorticoids/pharmacology
MH  - Humans
MH  - Interleukin-1/pharmacology
MH  - Nitric Oxide/*biosynthesis/chemistry/physiology
MH  - Nitric Oxide Synthase
MH  - Platelet Activating Factor/physiology
MH  - Shock/classification/*metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology
RF  - 329
EDAT- 1995/02/01 00:00
MHDA- 1995/02/01 00:01
CRDT- 1995/02/01 00:00
PHST- 1995/02/01 00:00 [pubmed]
PHST- 1995/02/01 00:01 [medline]
PHST- 1995/02/01 00:00 [entrez]
PST - ppublish
SO  - New Horiz. 1995 Feb;3(1):2-32.