Gonadal steroids, vascular smooth muscle, cerebral circulation, estrogen, endothelium, nitric oxide, mitochondria, reactive oxygen species, androgen, testosterone
Torald Sollmann Award in Pharmacology, 2007, American Society for Pharmacology and Experimental Therapeutics
PhRMA Foundation Award in Excellence in Pharmacology/Toxicology 2007
UCI, Daniel D. Aldrich, Jr, Distinguished University Service Award, 2004-2005
University of California, Irvine Chancellors Award for Excellence in Undergraduate Research, 2004
Chair, UCI Academic Senate, UCI, 1990-1992
Established Investigator, American Heart Association (1982-1987)
Dr. Duckles is a neuroscientist and cardiovascular pharmacologist interested in the unique function of the cerebral circulation. Her research focused on two major areas: influence of gender and sex steroid hormones on vascular reactivity and effects of estrogen on mitochondrial function.
Dr. Duckles’ laboratory discovered a novel effect of estrogen on mitochondrial function. Chronic estrogen treatment increases mitochondrial efficiency and reduces oxidative stress in cerebral blood vessels. Estrogen treatment increases levels of specific proteins in cerebrovascular mitochondria, including ERa, cytochrome c, subunits I and IV of complex IV, and Mn superoxide dismutase. Functional assays of mitochondria show that estrogen increases enzyme activity, but mitochondrial production of H2O2 is decreased. Furthermore, estrogen decreases superoxide production in mitochondria. These novel findings suggest that vascular protection by estrogen may be mediated, in part, by modulation of mitochondrial function. These actions of estrogen may also contribute to the longer lifespan of women.
Dr. Duckles’ work also demonstrated that chronic estrogen treatment increases vasodilator function of cerebral microvessels. After chronic estrogen treatment, there is a substantial up-regulation of endothelial function, with greater production of the potent vasodilators, NO and prostacyclin. Estrogen treatment results in increased levels of NO synthase, cyclooxygenase-1 and prostacyclin synthase. In contrast testosterone treatment increases contraction of cerebral blood vessels, effects dependent on a reduction in endothelial derived hyperpolarizing factor.
Estrogen and testosterone also have opposite effects on vascular inflammation in the cerebral circulation. Estrogen suppresses the vascular inflammatory response, while testosterone augments vascular inflammation. All of these effects may contribute to the well-known gender differences in the morbidity and mortality of stroke as well as the neuroprotective effects of estrogen.
Gonzales, RJ, Krause, DN, and Duckles, SP: Testosterone suppresses endothelium-dependent dilation of rat middle cerebral arteries. American Journal of Physiology: Heart and Circulatory Physiology, 286: 552-560, 2004.
Ospina, J.A., Brevig, H.N., Krause, D.N. and Duckles, S.P.: Estrogen suppresses IL-1?-mediated induction of COX-2 pathway in rat cerebral blood vessels. American Journal of Physiology: Heart and Circulatory Physiology 286: H2010-H2019, 2004.
Li, X, Geary, G.G., Gonzales, R., Krause, D.N. and S. P. Duckles: Effect of estrogen on cerebrovascular prostaglandins is amplified in mice with dysfunctional NOS. American Journal of Physiology: Heart and Circulatory Physiology, 287: H588-H594, 2004.
Stirone, C., Boroujerdi, A., Duckles, S.P. and D.N. Krause: Estrogen receptor activation of phosphoinositide-3 kinase, Akt and nitric oxide signaling in cerebral blood vessels: rapid and long-term effects. Molecular Pharmacology 67: 105-113, 2005.
Gonzales, R.J., Ghaffari, A.A., Duckles, S.P. and Krause, D.N.: Testosterone increases thromboxane function in rat middle cerebral arteries. American Journal of Physiology: Heart and Circulatory Physiology 289: H578-H585, 2005.
Stirone, C, Duckles, SP, Krause, DN and Procaccio, V: Estrogen increases mitochondrial efficiency and reduces oxidative stress in cerebral blood vessels. Molecular Pharmacology 68:959-965, 2005.
Razmara, A, Krause, DN, and Duckles, SP: Testosterone augments endotoxin-mediated cerebrovascular inflammation in male rats. American Journal of Physiology: Heart and Circulatory Physiology. 289: H1843-1850, 2005.
Duckles, S.P., Krause, D.N., Stirone, C. and Procaccio, V.N.: Review: Estrogen and mitochondria: A new paradigm for vascular protection? Molecular Interventions 6: 26-35, 2006.
Sunday, L, Tran, MM, Krause, DN, and Duckles, SP: Estrogen and progestagens differentially modulate vascular proinflammatory factors. American Journal of Physiology: Endocrinology and Metabolism, 291: E261-E267, 2006.
Gonzales, RJ, Ansar, S, Duckles, SP and Krause, DN: Androgenic/estrogenic balance in the male rat cerebral circulation: Metabolic enzymes and sex steroid receptors. Journal of Cerebral Blood Flow and Metabolism 27: 1841-1852, 2007.
Sunday, L, Osuna, C, Krause, DN and Duckles, SP: Age alters cerebrovascular inflammation and effects of estrogen. American Journal of Physiology: Heart and Circulatory Physiology 292: H2333-H2340, 2007.
Razmara, A, Duckles, S.P, Krause, D.N., and Procaccio, V. Estrogen Suppresses Brain Mitochondrial Oxidative Stress in Female and Male Rats. Brain Research, 1176: 71-81, 2007.
Duckles, SP: 2007 ASPET Torald Sollmann Award: A Career in Pharmacology: In Search of Beauty and Joy. Molecular Interventions 7:183-189, 2007.
Razmara, A., Sunday, L., Stirone, C, Wang, X, Krause, DN, Duckles, SP and Procaccio, V.: Mitochondrial effects of estrogen are mediated by ER? in brain endothelial cells. Journal of Pharmacology and Experimental Therapeutics, 325: 782-790, 2008.
Miller, VM and Duckles, SP: Vascular actions of estrogens: Functional implications. Pharmacological Reviews, 60: 210-241, 2008.
Gonzales, RJ, Duckles, SP and Krause, DN: Dihydrotestosterone stimulates cerebrovascular inflammation through NFkB, modulating contractile function, Journal of Cerebral Blood Flow and Metabolism, 29: 244-253, 2009.
American Society for Pharmacology and Experimental Therapeutics, President, 1997-98
Society for Neuroscience
International Union of Basic and Clinical Pharmacology, President (2006-2010), Secretary-General (2002-2006)
British Pharmacological Society, Honorary Fellow, 2005
Interim Chair, Department of Pharmacology
UC Irvine 2000—2006