Estrogen treatment enhances nitric oxide bioavailability in normotensive but not hypertensive rats

Hamilton, C., Groves, S., Carswell, H., Brosnan, M., Graham, D. and Dominiczak, A. (2006) Estrogen treatment enhances nitric oxide bioavailability in normotensive but not hypertensive rats. American Journal of Hypertension, 19(8), pp. 859-866. (doi: 10.1016/j.amjhyper.2006.01.008)

Abstract

Background: The effects of estrogen on endothelial function remain controversial. Endothelial function is perturbed in hypertension. We aimed to determine whether pre-existing hypertension can modify endothelial-dependent responses to estrogen. Methods: We compared the effects of estrogen replacement on endothelial function in healthy female adult Wistar Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP). Basal and carbachol-stimulated nitric oxide (NO) bioavailability were studied in carotid artery rings in ovariectomized animals treated with estrogen or placebo for 2 weeks in vivo, or after 1 h of incubation in vitro. Basal NO bioavailability was defined as the increase in pressor responses in phenylephrine in the presence of NO synthase blockade. Superoxide (O2−) levels in aortas were measured by lucigenin chemiluminescence and endothelial NO synthase (eNOS) protein levels by Western blotting. Results: Basal NO bioavailability was increased in WKY treated with estrogen for 2 weeks compared to placebo. In contrast, no change in NO bioavailability was observed in SHRSP. The O2− levels were higher in SHRSP than in WKY but unaffected by estrogen treatment in either strain. In WKY, but not in SHRSP, estrogen caused upregulation of eNOS. Similarly in vitro exposure to estrogen increased NO bioavailability in WKY but had no effect in SHRSP. In WKY, co-exposure to estrogen and LY294002, a PI3 kinase inhibitor, abrogated the effect of estrogen. Conclusions: The inability of estrogen to improve endothelial function in SHRSP may relate to a defect in eNOS activation pathways in this hypertensive rat strain.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Hamilton, Dr Carlene and Dominiczak, Professor Anna
• Authors: Hamilton, C., Groves, S., Carswell, H., Brosnan, M., Graham, D., and Dominiczak, A.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: American Journal of Hypertension
• ISSN: 0895-7061