Duncan, A. C., Petrie, J. R. , Brosnan, M. J., Devlin, A. M., Bass, R. A., Charnock-Jones, D. S., Connell, J. M., Dominiczak, A. F. and Lumsden, M. A. (2002) Is estradiol cardioprotection a nitric oxide-mediated effect? Human Reproduction, 17(7), pp. 1918-1924. (doi: 10.1093/humrep/17.7.1918)
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Abstract
BACKGROUND: Estradiol exerts a number of biological effects that support extensive observational data suggesting a protective role for estrogen in cardiovascular disease prevention. These include effects on lipid and carbohydrate metabolism, coagulation/fibrinolysis as well as a possible effect on vascular reactivity. It has been proposed that this might be mediated by vascular endothelial nitric oxide (NO) production. Accordingly, we designed complementary in-vivo and in-vitro studies to investigate this hypothesis further.<p></p> METHODS: Firstly, in a group of 10 healthy post-menopausal women, bilateral venous occlusion plethysmography was used to examine forearm vasoconstrictor responses to intrabrachial N-G-monomethyl-l-arginine (l-NMMA; a substrate inhibitor of nitric oxide synthase) both before and after 4 weeks of treatment with transdermal 17beta-estradiol (E-2) (80 mug/day). Secondly, we examined the direct effects of acute (24 h) and chronic (7 days) treatment with E-2 (10 pmol/l and 10 nmol/l) on endothelial nitric oxide synthase (eNOS) gene expression in cultured human aortic endothelial cells.<p></p> RESULTS: No significant differences were observed between the vasoconstrictor responses to l-NMMA (2, 4, 8 mumol/min) before and after E-2 treatment. Comparison of E-2-treated endothelial cells with control cells showed no significant increase in eNOS mRNA expression following either acute or chronic estradiol treatment.<p></p> CONCLUSIONS: The present studies do not provide evidence for an eNOS-mediated cardioprotective response to estrogen and therefore suggest that additional mechanisms other than the endothelial NO system may have an important role in the cardiovascular effects of estrogen.<p></p>
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Dominiczak, Professor Anna and Lumsden, Professor Mary and Petrie, Professor John and Connell, Professor John |
Authors: | Duncan, A. C., Petrie, J. R., Brosnan, M. J., Devlin, A. M., Bass, R. A., Charnock-Jones, D. S., Connell, J. M., Dominiczak, A. F., and Lumsden, M. A. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > General Practice and Primary Care College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > MRC/CSO SPHSU College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities |
Journal Name: | Human Reproduction |
Publisher: | Oxford University Press |
ISSN: | 0268-1161 |
ISSN (Online): | 1460-2350 |
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