PMID- 7472555
OWN - NLM
STAT- MEDLINE
DCOM- 19951128
LR  - 20131121
IS  - 0022-3085 (Print)
IS  - 0022-3085 (Linking)
VI  - 83
IP  - 5
DP  - 1995 Nov
TI  - Hemin activation of an inducible isoform of nitric oxide synthase in vascular 
      smooth-muscle cells.
PG  - 862-6
AB  - Hemin is a prominent breakdown product of hemoglobin, and high levels of hemin 
      are found in the cerebrospinal fluid during subarachnoid hemorrhage-induced 
      vasospasm. The possible role of hemin in modifying vascular function was examined 
      in the present study by testing its effects on nitric oxide synthase (NOS) 
      activity in cultured rat aortic smooth-muscle cells. Nitric oxide synthase 
      activity was estimated from the amounts of accumulated nitrite and nitrate, which 
      are oxidative products of nitric oxide (NO). Hemin (1-100 microM) increased the 
      levels of nitrite and nitrate in culture medium in a dose- and time-dependent 
      manner. The hemin-induced elevation of nitrite and nitrate was inhibited 
      significantly by the NOS inhibitor, N omega-nitro-L-arginine (300 microM), and by 
      the protein synthesis inhibitor, cycloheximide (5 micrograms/ml). These results 
      indicate that hemin is capable of stimulating the expression of an inducible 
      isoform of NOS (iNOS) in vascular smooth muscle. Transcriptional expression of 
      iNOS is known to cause injurious effects on the maintenance of cellular 
      homeostasis by generating extremely high levels of NO. The generation of hemin 
      from methemoglobin during hemolysis of a subarachnoid blood clot could therefore 
      stimulate an excessive production of NO in vascular smooth-muscle cells. It is 
      postulated that this series of events contributes to the development of vascular 
      injury associated with cerebral vasospasm after aneurysmal subarachnoid 
      hemorrhage.
FAU - Suzuki, S
AU  - Suzuki S
AD  - Department of Neurological Surgery, University of Virginia Health Sciences 
      Center, Charlottesville, USA.
FAU - Kassell, N F
AU  - Kassell NF
FAU - Lee, K S
AU  - Lee KS
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Neurosurg
JT  - Journal of neurosurgery
JID - 0253357
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Isoenzymes)
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 2149-70-4 (Nitroarginine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 743LRP9S7N (Hemin)
RN  - 94ZLA3W45F (Arginine)
RN  - 98600C0908 (Cycloheximide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
SB  - IM
CIN - J Neurosurg. 1997 Apr;86(4):741-2. PMID: 9120649
MH  - Analysis of Variance
MH  - Animals
MH  - Arginine/analogs & derivatives/pharmacology
MH  - Cells, Cultured
MH  - Cycloheximide/pharmacology
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Hemin/pharmacology/*physiology
MH  - Isoenzymes/*metabolism
MH  - Muscle, Smooth, Vascular/drug effects/enzymology/*metabolism
MH  - Nitrates/metabolism
MH  - Nitric Oxide/biosynthesis
MH  - Nitric Oxide Synthase/antagonists & inhibitors/*metabolism
MH  - Nitrites/metabolism
MH  - Nitroarginine
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Rats
MH  - Stimulation, Chemical
EDAT- 1995/11/01 00:00
MHDA- 1995/11/01 00:01
CRDT- 1995/11/01 00:00
PHST- 1995/11/01 00:00 [pubmed]
PHST- 1995/11/01 00:01 [medline]
PHST- 1995/11/01 00:00 [entrez]
AID - 10.3171/jns.1995.83.5.0862 [doi]
PST - ppublish
SO  - J Neurosurg. 1995 Nov;83(5):862-6. doi: 10.3171/jns.1995.83.5.0862.