| First Author | Enkhjargal B | Year | 2014 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 34 |
| Issue | 7 | Pages | 1505-13 |
| PubMed ID | 24855056 | Mgi Jnum | J:223897 |
| Mgi Id | MGI:5660589 | Doi | 10.1161/ATVBAHA.114.303735 |
| Citation | Enkhjargal B, et al. (2014) Endothelial AMP-activated protein kinase regulates blood pressure and coronary flow responses through hyperpolarization mechanism in mice. Arterioscler Thromb Vasc Biol 34(7):1505-13 |
| abstractText | OBJECTIVE: Vascular endothelium plays an important role to maintain cardiovascular homeostasis through several mechanisms, including endothelium-dependent hyperpolarization (EDH). We have recently demonstrated that EDH is involved in endothelial metabolic regulation in mice. However, it remains to be examined whether AMP-activated protein kinase (AMPK), an important metabolic regulator, is involved in EDH and if so, whether endothelial AMPK (eAMPK) plays a role for circulatory regulation. APPROACH AND RESULTS: We examined the role of eAMPK in EDH, using mice with endothelium-specific deficiency of alpha-catalytic subunit of AMPK, either alpha1 (eAMPKalpha1 (-/-)alpha2 (+/+)) or alpha2 (eAMPKalpha1 (+/+)alpha2 (-/-)) alone or both of them (eAMPKalpha1 (-/-)alpha2 (-/-)). We performed telemetry, organ chamber, electrophysiological, and Langendorff experiments to examine blood pressure, vascular responses, hyperpolarization of membrane potential, and coronary flow responses, respectively. Hypertension was noted throughout the day in eAMPKalpha1 (-/-)alpha2 (-/-) and eAMPKalpha1 (-/-)alpha2 (+/+) but not in eAMPKalpha1 (+/+)alpha2 (-/-) mice when compared with respective control. Importantly, endothelium-dependent relaxations, EDH, and coronary flow increase were all significantly reduced in eAMPKalpha1 (-/-)alpha2 (-/-) and eAMPKalpha1 (-/-)alpha2 (+/+) but not in eAMPKalpha1 (+/+)alpha2 (-/-) mice. In contrast, endothelium-independent relaxations to sodium nitroprusside (a NO donor), NS-1619 (a Ca(2+)-activated K(+) channel opener), and exogenous H2O2 were almost comparable among the groups. In eAMPKalpha1 (-/-)alpha2 (-/-) mice, antihypertensive treatment with hydralazine or long-term treatment with metformin (a stimulator of AMPK) failed to restore EDH-mediated responses. CONCLUSIONS: These results provide the first direct evidence that alpha1 subunit of eAMPK substantially mediates EDH responses of microvessels and regulates blood pressure and coronary flow responses in mice in vivo, demonstrating the novel role of eAMPK in cardiovascular homeostasis. |
