PMID- 18172111
OWN - NLM
STAT- MEDLINE
DCOM- 20080221
LR  - 20161124
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 49
IP  - 1
DP  - 2008 Jan
TI  - The role of nitric oxide and cGMP in somatostatin's protection against retinal 
      ischemia.
PG  - 342-9
LID - 10.1167/iovs.07-0341 [doi]
AB  - PURPOSE: To investigate whether nitric oxide (NO) and/or cGMP protects the retina 
      from chemical ischemia and underlie somatostatin's neuroprotective effects. 
      METHODS: Eyecups of female Sprague-Dawley rats were incubated with PBS or the 
      chemical ischemia mixture [iodoacetic acid (5 mM)/sodium cyanate (25 mM)] in the 
      absence or presence of (1) arginine (0.05-2.0 mM), the substrate of nitric oxide 
      synthase (NOS); (2) the NO donors sodium nitroprusside (SNP; 0.25-4.0 mM), 
      3-morpholinosydnonimine (SIN-1; 0.1, 0.3, 1.0 mM), SIN-1 (0.1 mM)/L-cysteine (5 
      mM, peroxynitrite scavenger), and NONOate (1, 5, 10 microM, slow NO releaser); 
      (3) 8-Br-cGMP (0.1, 0.5, 1.0 mM); (4) BIM23014 (sst(2) receptor agonist; 1 
      microM), alone or in the presence of (5) the NOS inhibitor 
      N(gamma)-monomethyl-L-arginine (NMMA; 0.5 mM); or (6) the guanylyl cyclase 
      inhibitors 1H-[1,2,4]oxadiazolol [4,3-a]quinoxalin-1-one (ODQ;100 microM) and 
      NS2028 (50 microM) for 60 minutes, at 5%CO(2)/air in 37 degrees C. The effect of 
      SIN-1 (0.1, 0.3, 1.0, or 3.0 mM) on the retina was also examined. Subsequently, 
      the eyecups were fixed and sectioned for choline acetyltransferase (ChAT) 
      immunoreactivity and TUNEL staining. RESULTS: Arginine and SNP had no effect on 
      the chemical ischemia-induced toxicity. SIN-1, NONOate, and 8-Br-cGMP produced a 
      concentration-dependent protective effect, as shown by ChAT immunoreactivity. 
      TUNEL staining also confirmed the neuroprotective effect of these agents. 
      L-cysteine partially reduced the SIN-1-induced protective effect. SIN-1 alone was 
      toxic only at the highest concentration used (3 mM). NMMA, ODQ, and NS2028 
      reversed the protective effect of BIM23014. CONCLUSIONS: The results suggest that 
      a NO/peroxynitrite/cGMP mechanism may be important in the protection of the 
      retina from ischemic insult. Furthermore, the NO/sGC/cGMP pathway is involved in 
      the neuroprotective effects of sst(2) ligands against retinal ischemia.
FAU - Mastrodimou, Niki
AU  - Mastrodimou N
AD  - Laboratory of Pharmacology, Department of Basic Sciences, Faculty of Medicine, 
      University of Crete, Heraklion, Crete, Greece.
FAU - Kiagiadaki, Foteini
AU  - Kiagiadaki F
FAU - Thermos, Kyriaki
AU  - Thermos K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Peptides, Cyclic)
RN  - 0G3DE8943Y (lanreotide)
RN  - 136587-13-8 (spermine nitric oxide complex)
RN  - 2FZ7Y3VOQX (Spermine)
RN  - 31356-94-2 (8-bromocyclic GMP)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 51110-01-1 (Somatostatin)
RN  - 5O5U71P6VQ (linsidomine)
RN  - D46583G77X (Molsidomine)
RN  - EC 2.3.1.6 (Choline O-Acetyltransferase)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Animals
MH  - Choline O-Acetyltransferase/metabolism
MH  - Cyclic GMP/analogs & derivatives/pharmacology/*physiology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Fluorescent Antibody Technique, Indirect
MH  - In Situ Nick-End Labeling
MH  - Ischemia/chemically induced/metabolism/pathology/*prevention & control
MH  - Molsidomine/analogs & derivatives/pharmacology
MH  - Nitric Oxide/*physiology
MH  - Peptides, Cyclic/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retinal Diseases/chemically induced/metabolism/pathology/*prevention & control
MH  - Retinal Vessels/*drug effects
MH  - Somatostatin/*analogs & derivatives/pharmacology
MH  - Spermine/analogs & derivatives/pharmacology
EDAT- 2008/01/04 09:00
MHDA- 2008/02/22 09:00
CRDT- 2008/01/04 09:00
PHST- 2008/01/04 09:00 [pubmed]
PHST- 2008/02/22 09:00 [medline]
PHST- 2008/01/04 09:00 [entrez]
AID - 49/1/342 [pii]
AID - 10.1167/iovs.07-0341 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2008 Jan;49(1):342-9. doi: 10.1167/iovs.07-0341.