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Normal vascular development in mice deficient in endothelial NO synthase: possible role of neuronal NO synthase.
Mol Vis. 2003 Oct 08; 9:549-58.MV

Abstract

PURPOSE

Nitric oxide formation by nitric oxide synthase (NOS) has been implicated in vascular injury and retinal neovascularization during oxygen-induced retinopathy. However, the role of NOS in normal retinal vascular development and growth has not been studied. The purpose of these experiments was to characterize the expression of NOS in relation to vascular development and to determine the effect of deleting endothelial NOS (eNOS) on this process.

METHODS

Retinal vascular development was analyzed in 150 eNOS+/+ and eNOS-/- mice ranging from 1 day to 6 months old by using a combination of morphometric and biochemical approaches. The pattern of vascular development was analyzed in retinal tissue sections and whole-mount preparations labeled with fluorescein-conjugated Griffonia simplicifolia lectin. Analysis of vascular density and arterial diameter were performed with the lectin-labeled whole-mounts using computer-assisted morphometry. NO production was quantified by measuring retinal levels of nitrate/nitrite accumulation using the Greiss reaction. Western blotting techniques with isoform-specific NOS antibodies were used to evaluate differences in levels of NOS protein expression. Retinal distribution of nNOS was characterized using nNOS immunocytochemistry and NADPH diaphorase histochemistry.

RESULTS

These analyses showed that the rate and pattern of retinal vascular development in eNOS-/- mice were comparable with those in wild-type control mice. Measurement of vascular density showed no significant differences between the two strains. The amount of NO production in the eNOS-/- retina was also equivalent to that in the eNOS+/+ retina. Analysis of nNOS expression within the eNOS+/+ and eNOS-/- mice showed similar levels of total nNOS protein in the two strains. Inducible NOS was not detected in either strain. Studies of nNOS distribution showed intense labeling of the deep capillary plexus in the eNOS-/- retina. This was not seen in the wild-type retinas. The number of neuronal cells showing NADPH-diaphorase activity was also significantly increased in the eNOS-/- mice.

CONCLUSIONS

Development of the retinal vasculature occurs normally without eNOS. The observations of similar levels of NO production, perivascular redistribution of nNOS and increased numbers of NADPH-diaphorase reactive neurons in the eNOS-/- retinas suggest that increases in vascular-associated nNOS activity compensate for the eNOS deficiency in the developing mutant retina.

Authors+Show Affiliations

Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912-2500, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14551528

Citation

Al-Shabrawey, Mohamed, et al. "Normal Vascular Development in Mice Deficient in Endothelial NO Synthase: Possible Role of Neuronal NO Synthase." Molecular Vision, vol. 9, 2003, pp. 549-58.
Al-Shabrawey M, El-Remessy A, Gu X, et al. Normal vascular development in mice deficient in endothelial NO synthase: possible role of neuronal NO synthase. Mol Vis. 2003;9:549-58.
Al-Shabrawey, M., El-Remessy, A., Gu, X., Brooks, S. S., Hamed, M. S., Huang, P., & Caldwell, R. B. (2003). Normal vascular development in mice deficient in endothelial NO synthase: possible role of neuronal NO synthase. Molecular Vision, 9, 549-58.
Al-Shabrawey M, et al. Normal Vascular Development in Mice Deficient in Endothelial NO Synthase: Possible Role of Neuronal NO Synthase. Mol Vis. 2003 Oct 8;9:549-58. PubMed PMID: 14551528.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Normal vascular development in mice deficient in endothelial NO synthase: possible role of neuronal NO synthase. AU - Al-Shabrawey,Mohamed, AU - El-Remessy,Azza, AU - Gu,Xiaolin, AU - Brooks,Steven S, AU - Hamed,Mohamed S, AU - Huang,Paul, AU - Caldwell,Ruth B, Y1 - 2003/10/08/ PY - 2003/10/11/pubmed PY - 2003/12/10/medline PY - 2003/10/11/entrez SP - 549 EP - 58 JF - Molecular vision JO - Mol Vis VL - 9 N2 - PURPOSE: Nitric oxide formation by nitric oxide synthase (NOS) has been implicated in vascular injury and retinal neovascularization during oxygen-induced retinopathy. However, the role of NOS in normal retinal vascular development and growth has not been studied. The purpose of these experiments was to characterize the expression of NOS in relation to vascular development and to determine the effect of deleting endothelial NOS (eNOS) on this process. METHODS: Retinal vascular development was analyzed in 150 eNOS+/+ and eNOS-/- mice ranging from 1 day to 6 months old by using a combination of morphometric and biochemical approaches. The pattern of vascular development was analyzed in retinal tissue sections and whole-mount preparations labeled with fluorescein-conjugated Griffonia simplicifolia lectin. Analysis of vascular density and arterial diameter were performed with the lectin-labeled whole-mounts using computer-assisted morphometry. NO production was quantified by measuring retinal levels of nitrate/nitrite accumulation using the Greiss reaction. Western blotting techniques with isoform-specific NOS antibodies were used to evaluate differences in levels of NOS protein expression. Retinal distribution of nNOS was characterized using nNOS immunocytochemistry and NADPH diaphorase histochemistry. RESULTS: These analyses showed that the rate and pattern of retinal vascular development in eNOS-/- mice were comparable with those in wild-type control mice. Measurement of vascular density showed no significant differences between the two strains. The amount of NO production in the eNOS-/- retina was also equivalent to that in the eNOS+/+ retina. Analysis of nNOS expression within the eNOS+/+ and eNOS-/- mice showed similar levels of total nNOS protein in the two strains. Inducible NOS was not detected in either strain. Studies of nNOS distribution showed intense labeling of the deep capillary plexus in the eNOS-/- retina. This was not seen in the wild-type retinas. The number of neuronal cells showing NADPH-diaphorase activity was also significantly increased in the eNOS-/- mice. CONCLUSIONS: Development of the retinal vasculature occurs normally without eNOS. The observations of similar levels of NO production, perivascular redistribution of nNOS and increased numbers of NADPH-diaphorase reactive neurons in the eNOS-/- retinas suggest that increases in vascular-associated nNOS activity compensate for the eNOS deficiency in the developing mutant retina. SN - 1090-0535 UR - https://www.unboundmedicine.com/medline/citation/14551528/Normal_vascular_development_in_mice_deficient_in_endothelial_NO_synthase:_possible_role_of_neuronal_NO_synthase_ DB - PRIME DP - Unbound Medicine ER -