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PI3-kinase-induced hyperreactivity in DOCA-salt hypertension is independent of GSK-3 activity.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Watts, Stephanie W. |
| Copyright Year | 2003 |
| Abstract | Phosphatidylinositol 3-kinase (PI3K) activity is increased in aortae from deoxycorticosterone (DOCA)-salt rats and enhanced PI3K activity contributes to the arterial hyperreactivity in these animals. Because PI3K activity is increased in DOCA-salt hypertension, we postulated that phosphorylation of Akt and glycogen synthase kinase 3 (GSK-3), serine threonine kinases that are downstream of PI3K, would be increased in DOCA-salt hypertension. In this study, we focused on GSK-3. Because GSK-3 activity is reduced by phosphorylation, we expected that its activity would be reduced in DOCA-salt hypertensive arteries and that reduced GSK-3 activity could contribute to enhanced adrenergic signaling and vascular smooth muscle hypertrophy that augment the heightened contractile response in DOCA-salt hypertension. Surprisingly, we observed a decrease in phosphorylation of GSK-3, indicating an increase in GSK-3 activity. To determine whether increased GSK-3 activity contributes to altered arterial reactivity in DOCA-salt animals, we measured isometric contraction to norepinephrine (NE) in the presence and absence of PI3K or GSK-3 inhibition. Addition of LY294002 (20 micromol/L), a PI3K inhibitor, resulted in a rightward shift in response to NE and normalized the NE-induced contractions in the DOCA hypertensive vessels. SB415286, a GSK-3 inhibitor, resulted in a slight rightward shift in response to NE in the DOCA-salt vessels. Thus, enhanced GSK-3 activity modestly augments the effects of PI3K but does not appear to contribute greatly to the altered arterial reactivity in DOCA-salt hypertension. |
| Starting Page | 898 |
| Ending Page | 902 |
| Page Count | 5 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://hyper.ahajournals.org/content/hypertensionaha/41/4/898.full.pdf |
| PubMed reference number | 12629035v1 |
| Volume Number | 41 |
| Issue Number | 4 |
| Journal | Hypertension |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 1-Phosphatidylinositol 3-Kinase Blood Vessel Desoxycorticosterone acetate Glycogen (Starch) Synthase Glycogen Synthase Kinase 3 Glycogen Synthase Kinases Hypertensive disease Isometric Contraction LY 294002 Micromole Muscle, Smooth, Vascular Norepinephrine Protein-Serine-Threonine Kinases Proto-Oncogene Proteins c-akt SB 415286 Smooth muscle (tissue) Sodium Chloride, Dietary Threonine smooth muscle hypertrophy |
| Content Type | Text |
| Resource Type | Article |
