Phosphorylated endothelial NOS Ser1177 via the PI3K/Akt pathway is depressed in the brain of stroke-prone spontaneously hypertensive rat.
Stroke-prone spontaneously hypertensive rats (SHRSP) demonstrate impaired endothelium-dependent relaxation and often develop brain injuries. We investigated whether the regulatory mechanism for endothelial NOS (eNOS) phosphorylation and activation is altered in the cerebral cortex of SHRSP at a younger age. Western blot analysis revealed a low ratio of phosphor-eNOS (Ser1177) to total eNOS in SHRSP at 10 weeks of age. In addition, urinary nitric oxide metabolites (ie, nitrate and nitrite) were decreased compared with normal control WKY rats. Likewise, Akt phosphorylation (especially Ser473) was significantly reduced, with no changes in total Akt. Furthermore, the amount of the phosphatidylinositol 3-kinase (PI3K) was upstream of Akt was diminished, although attenuation of the PI3K/Akt pathway was not an effect of mTOR, another downstream target of Akt. Our findings indicate that abnormalities of the PI3K/Akt pathway in the cerebral cortex are involved in the impaired eNOS phosphorylation and activation in SHRSP.
Yoshitomi
Hisae
H
School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan. hisa4403@mukogawa-u.ac.jp
Xu
Qiang
Q
Gao
Ming
M
Yamori
Yukio
Y
D000367:Age Factors; D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D001835:Body Weight; D002540:Cerebral Cortex / Q000201:enzymology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D006973:Hypertension / Q000150:complications* / Q000201:enzymology; D008297:Male; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D009573:Nitrites / Q000652:urine; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D012694:Serine; D015398:Signal Transduction; D020521:Stroke / Q000201:enzymology / Q000209:etiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D012694:Serine; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C546845:mTOR protein, rat; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases