Age-dependent increase in activity of eukaryotic elongation factor 2 kinase in mesenteric arteries from spontaneously hypertensive rats.

Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) negatively regulates protein translation through the phosphorylation of its specific substrate, eEF2. We previously found that expression of eEF2K was increased in arteries from 13-15-week-old spontaneously hypertensive rats (SHR) as well as in left ventricles of cardiac hypertrophy models. Furthermore, we demonstrated that eEF2K mediates the development of essential hypertension and pulmonary arterial hypertension in animal models. Protein expression changes with age during development of hypertension in SHR. In the present study, we examined whether activity and expression of eEF2K change in isolated mesenteric arteries dependent on the age. After superior mesenteric arteries were isolated from 4-10-week-old Wistar Kyoto rats (WKY) and SHR, Western blotting was performed. The phosphorylation of eEF2K at Ser500, an activating phosphorylation site, was increased in the arteries from 10-week-old SHR, whereas the phosphorylation of eEF2K at Ser366, an inactivating phosphorylation site, was increased in the arteries from 4-5-week-old SHR compared with WKY. The expression of eEF2K was increased in the arteries from 10-week-old SHR compared with WKY. The phosphorylation of eEF2 at Thr56 was decreased in the arteries from 4-5-week-old SHR, whereas it was increased in the arteries from 10-week-old SHR compared with WKY. We for the first time revealed that eEF2K activity is lower in prehypertensive stage but higher in hypertensive stage in SHR, suggesting that an inhibition of eEF2K activity may be a potential therapeutic strategy for the treatment of essential hypertension.