This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Komesaroff, P. A. Articles by Westerman, R. A. Search for Related Content PubMed PubMed Citation Articles by Komesaroff, P. A. Articles by Westerman, R. A.

A Novel, Nongenomic Action of Estrogen on the Cardiovascular System

Baker Medical Research Institute (P.A.K., C.V.S.B.), PO Box 348, Prahran, Victoria 3181, Australia and International Diabetes Institute (R.A.W.), Kooyong Road, Caulfield, Victoria, Australia

Address all correspondence and requests for reprints to: P.A. Komesaroff, Baker Medical Research Institute, P.O. Box 348, Prahran, Victoria 3181, Australia; E-mail: Paul.Komesaroff{at}Baker.Edu.Au

To examine the time course and mechanisms of action of single doses of estrogen on the skin microvasculature, two double-blind placebo-controlled cross-over studies were conducted in healthy young men using the noninvasive technique of laser Doppler velocimetry with iontophoretic application of vasodilator substances. Estradiol (2 mg sublingually) produced a significant increase in the response to the endothelial vasodilator acetylcholine (ACh) after 15 min, but not after 20 or 30 min. The mean plasma estradiol concentration increased from 89.4 ± 9 pmol/L at baseline to 486.6 ± 218 pmol/L at 15 min. An iv bolus of 25 mg conjugated equine estrogens produced significant increases in the responses to ACh at 15 and 20 min but not at 30 min. There was no change in responses to the nonendothelial vasodilators sodium nitroprusside or nicotine, and administration of placebo produced no change in ACh responses at any time point. These experiments show that, at plasma estradiol concentrations within the physiological range for premenopausal women, estrogens act directly on the cutaneous microvasculature through a rapid onset, rapid offset, nongenomic mechanism that is specific to the endothelium; in addition, it supports the view that estrogens can act on the male cardiovascular system in a manner that is potentially clinically beneficial.

This article has been cited by other articles:

				B. Xue, Y. Zhao, A. K. Johnson, and M. Hay Central estrogen inhibition of angiotensin II-induced hypertension in male mice and the role of reactive oxygen species Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1025 - H1032. [Abstract] [Full Text] [PDF]

				M. R. I. Williams, T. Dawood, S. Ling, A. Dai, R. Lew, K. Myles, J. W. Funder, K. Sudhir, and P. A. Komesaroff Dehydroepiandrosterone Increases Endothelial Cell Proliferation in Vitro and Improves Endothelial Function in Vivo by Mechanisms Independent of Androgen and Estrogen Receptors J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4708 - 4715. [Abstract] [Full Text] [PDF]

				G. A. Head, V. R. Obeyesekere, M. E. Jones, E. R. Simpson, and Z. S. Krozowski Aromatase-Deficient (ArKO) Mice Have Reduced Blood Pressure and Baroreflex Sensitivity Endocrinology, September 1, 2004; 145(9): 4286 - 4291. [Abstract] [Full Text] [PDF]

				L. Maffei, Y. Murata, V. Rochira, G. Tubert, C. Aranda, M. Vazquez, C. D. Clyne, S. Davis, E. R. Simpson, and C. Carani Dysmetabolic Syndrome in a Man with a Novel Mutation of the Aromatase Gene: Effects of Testosterone, Alendronate, and Estradiol Treatment J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 61 - 70. [Abstract] [Full Text] [PDF]

				A. C. Calkin, K. Sudhir, S. Honisett, M. R. I. Williams, T. Dawood, and P. A. Komesaroff Rapid Potentiation of Endothelium-Dependent Vasodilation by Estradiol in Postmenopausal Women Is Mediated via Cyclooxygenase 2 J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 5072 - 5075. [Abstract] [Full Text] [PDF]

				M. R. I. Williams, R. A. Westerman, B. A. Kingwell, J. Paige, P. A. Blombery, K. Sudhir, and P. A. Komesaroff Variations in Endothelial Function and Arterial Compliance during the Menstrual Cycle J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5389 - 5395. [Abstract] [Full Text] [PDF]

				P. A. Komesaroff, M. Fullerton, M. D. Esler, A. Dart, G. Jennings, and K. Sudhir Low-Dose Estrogen Supplementation Improves Vascular Function in Hypogonadal Men Hypertension, November 1, 2001; 38(5): 1011 - 1016. [Abstract] [Full Text] [PDF]

				S. F. Palter, A. B. Tavares, A. Hourvitz, J. D. Veldhuis, and E. Y. Adashi Are Estrogens of Import to Primate/Human Ovarian Folliculogenesis? Endocr. Rev., June 1, 2001; 22(3): 389 - 424. [Abstract] [Full Text] [PDF]

				S. C. Manolagas and S. Kousteni Perspective: Nonreproductive Sites of Action of Reproductive Hormones Endocrinology, June 1, 2001; 142(6): 2200 - 2204. [Full Text] [PDF]

				J Dupont and D Le Roith Insulin-like growth factor 1 and oestradiol promote cell proliferation of MCF-7 breast cancer cells: new insights into their synergistic effects Mol. Pathol., June 1, 2001; 54(3): 149 - 154. [Abstract] [Full Text]

				M. T. Littleton-Kearney, D. M. Agnew, R. J. Traystman, and P. D. Hurn Effects of estrogen on cerebral blood flow and pial microvasculature in rabbits Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1208 - H1214. [Abstract] [Full Text] [PDF]

				K. Sudhir and P. A. Komesaroff Cardiovascular Actions of Estrogens in Men J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3411 - 3415. [Full Text] [PDF]

				A. M. McNeill, N. Kim, S. P. Duckles, D. N. Krause, and H. A. Kontos Chronic Estrogen Treatment Increases Levels of Endothelial Nitric Oxide Synthase Protein in Rat Cerebral Microvessels • Editorial Comment Stroke, October 1, 1999; 30(10): 2186 - 2190. [Abstract] [Full Text] [PDF]

				S. Ling, P. J. Little, M. R. I. Williams, A. Dai, K. Hashimura, J.-P. Liu, P. A. Komesaroff, and K. Sudhir High glucose abolishes the antiproliferative effect of 17beta -estradiol in human vascular smooth muscle cells Am J Physiol Endocrinol Metab, April 1, 2002; 282(4): E746 - E751. [Abstract] [Full Text] [PDF]