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Inducible nitric oxide synthase subserves cholinergic vasodilation in retina

Published online by Cambridge University Press:  02 August 2005

ALEJANDRO BERRA ,
SABRINA GANZINELLI ,
MARIO SARAVIA ,
ENRI BORDA  and
LEONOR STERIN-BORDA
ALEJANDRO BERRA
Affiliation:
Department of Pathology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina
SABRINA GANZINELLI
Affiliation:
Pharmacology Unit, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina
MARIO SARAVIA
Affiliation:
Department of Pathology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina
ENRI BORDA
Affiliation:
Pharmacology Unit, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina The Argentine National Research Council (CONICET), Buenos Aires, Argentina
LEONOR STERIN-BORDA
Affiliation:
Pharmacology Unit, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina The Argentine National Research Council (CONICET), Buenos Aires, Argentina
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Abstract

In this paper, we investigate the role of muscarinic acetylcholine receptor (mAChR) activity in the regulation of inducible (i) nitric oxide synthase (iNOS) expression and activity. The signaling pathway involved is also examined. These experiments also provide a link between mAChR activation and the nitric oxide (NO)-dependent regulation of retinal vascular diameter. The diameter of the retinal vessels at a distance of 1 disc diameter from the center of the optic disc was measured in rats using digital retinal photography, and both iNOS-mRNA gene expression and NOS were specifically measured using RT-PCR and [U-14C] citrulline assays, respectively. Stimulation of M1 and M3 mAChR with carbachol caused an increase in vessel diameter, in iNOS-mRNA levels and in NOS activity in the retina. Aminoguanidine, an inhibitor of iNOS, attenuated all these effects. Inhibitors of phospholipase C (PLC) and protein kinase C (PKC) but not calcium/calmodulin (CaM) prevented the muscarinic-dependent increase in iNOS-mRNA levels. The results obtained suggest that the activation of mAChR increases retinal vessel diameters by increasing the production of nitric oxide (NO) through iNOS activation and iNOS-mRNA gene expression. The mechanism appears to occur secondarily to stimulation of PLC and PKC enzymatic activity.

Keywords

RetinaCholinoceptorsNitric oxideNitric oxide synthaseInducible nitric oxide synthase
Type
Research Article
Information
Visual Neuroscience , Volume 22 , Issue 3 , May 2005 , pp. 371 - 377
Copyright
2005 Cambridge University Press

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