The phosphorylation state of eNOS modulates vascular reactivity and outcome of cerebral ischemia in vivo
Dmitriy N. Atochin, … , William C. Sessa, Paul L. Huang
Dmitriy N. Atochin, … , William C. Sessa, Paul L. Huang
Published July 2, 2007
Citation Information: J Clin Invest. 2007;117(7):1961-1967. https://doi.org/10.1172/JCI29877.
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Research Article Hematology

The phosphorylation state of eNOS modulates vascular reactivity and outcome of cerebral ischemia in vivo

Abstract

NO plays critical roles in vascular function. We show that modulation of the eNOS serine 1179 (S1179) phosphorylation site affects vascular reactivity and determines stroke size in vivo. Transgenic mice expressing only a phosphomimetic (S1179D) form of eNOS show greater vascular reactivity, develop less severe strokes, and have improved cerebral blood flow in a middle cerebral artery occlusion model than mice expressing an unphosphorylatable (S1179A) form. These results provide a molecular mechanism by which multiple diverse cardiovascular risks, such as diabetes and obesity, may be centrally integrated by eNOS phosphorylation in vivo to influence blood flow and cardiovascular disease. They also demonstrate the in vivo relevance of posttranslational modification of eNOS in vascular function.

Authors

Dmitriy N. Atochin, Annie Wang, Victor W.T. Liu, Jeffrey D. Critchlow, Ana Paula V. Dantas, Robin Looft-Wilson, Takahisa Murata, Salvatore Salomone, Hwa Kyoung Shin, Cenk Ayata, Michael A. Moskowitz, Thomas Michel, William C. Sessa, Paul L. Huang

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Figure 4

Effect of S1179D and S1179A mutations on vascular reactivity.

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Effect of S1179D and S1179A mutations on vascular reactivity. (A) Left c...
(A) Left common carotid arteries were constricted with phenylephrine (10–5 M) and then subjected to increasing doses of ACh from 1 × 10–9 to 1 × 10–5 M. S1179A/eNOS KO mice, n = 8; S1179D/eNOS KO mice, n = 8; eNOS KO mice, n = 6; and WT mice, n = 8. *P < 0.01 by 1-way ANOVA; †P < 0.05 by 1-way ANOVA. (B) Left common carotid arteries were treated with l-NAME (3 × 10–4 M) for 30 minutes, constricted with phenylephrine (10–5 M), and then subjected to increasing doses of SNP from 1 × 10–9 to 1 × 10–5 M. Data are expressed as mean ± SEM.