| First Author | Guivarc'h E | Year | 2020 |
| Journal | J Am Heart Assoc | Volume | 9 |
| Issue | 5 | Pages | e013895 |
| PubMed ID | 32102616 | Mgi Jnum | J:299787 |
| Mgi Id | MGI:6490670 | Doi | 10.1161/JAHA.119.013895 |
| Citation | Guivarc'h E, et al. (2020) Nuclear Activation Function 2 Estrogen Receptor alpha Attenuates Arterial and Renal Alterations Due to Aging and Hypertension in Female Mice. J Am Heart Assoc 9(5):e013895 |
| abstractText | Background The cardiovascular protective effects of estrogens in premenopausal women depend mainly on estrogen receptor alpha (ERalpha). ERalpha activates nuclear gene transcription regulation and membrane-initiated signaling. The latter plays a key role in estrogen-dependent activation of endothelial NO synthase. The goal of the present work was to determine the respective roles of the 2 ERalpha activities in endothelial function and cardiac and kidney damage in young and old female mice with hypertension, which is a major risk factor in postmenopausal women. Methods and Results Five- and 18-month-old female mice lacking either ERalpha (ERalpha(-/-)), the nuclear activating function AF2 of ERalpha (AF2 degrees ), or membrane-located ERalpha (C451A) were treated with angiotensin II (0.5 mg/kg per day) for 1 month. Systolic blood pressure, left ventricle weight, vascular reactivity, and kidney function were then assessed. Angiotensin II increased systolic blood pressure, ventricle weight, and vascular contractility in ERalpha(-/-) and AF2 degrees mice more than in wild-type and C451A mice, independent of age. In both the aorta and mesenteric resistance arteries, angiotensin II and aging reduced endothelium-dependent relaxation in all groups, but this effect was more pronounced in ERalpha(-/-) and AF2 degrees than in the wild-type and C451A mice. Kidney inflammation and oxidative stress, as well as blood urea and creatinine levels, were also more pronounced in old hypertensive ERalpha(-/-) and AF2 degrees than in old hypertensive wild-type and C451A mice. Conclusions The nuclear ERalpha-AF2 dependent function attenuates angiotensin II-dependent hypertension and protects target organs in aging mice, whereas membrane ERalpha signaling does not seem to play a role. |
