This proposal details a 5 year training program to develop the skills necessary to pursue independent research in basic science. The principal investigator, a board-certified Pediatrician completing the third year of fellowship training in Neonatology, is currently applying for an elective year of fellowship training to lay as strong a foundation as possible for a successful career in academic medicine. This training program centers upon studies of altered ovine coronary artery physiology following antenatal corticosteroid exposure. The global hypothesis is that dexamethasone-induced downregulation of coronary artery cyclooxygenase (COX)-depenendent prostaglandin and reactive oxygen species (ROS) production is an important aspect of fetal programming, resulting in heightened coronary artery tone. Such alterations in coronary artery reactivity could provide a mechanistic explaination for the observed associations between an adverse intrauterine environment, low birth weight and subsequent coronary artery disease. Dr. Jeffrey Segar will mentor the Pi's training with Dr. Fred Lamb acting as co-sponsor. They are well established investigators in ovine cardiovascular physiology, and their mutual interest in the study of coronary artery dysfunction 'fosters an intellectually stimulating collaborative environment that has already propelled others into successful research careers. Dr. Roghair's preliminary data demonstrating steroid-induced alterations in COX-mediated vascular reactivty in association with deceased basal ROS production has led to the evolution of the following specific aims: 1) define the role of prostaglandins in the fetal programming of coronary artery dysfunction; 2) test the hypothesis that early gestation dexamethasone exposure alters arachidonic acid-induced reactive oxygen species production; and 3) determine whether the observed alterations in conduit coronary artery reactivity are seen in physiologically-relevant resistance coronary arterioles. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08HD050359-01A1
Application #
7099218
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Raiten, Daniel J
Project Start
2006-08-10
Project End
2011-07-31
Budget Start
2006-08-10
Budget End
2007-07-31
Support Year
1
Fiscal Year
2006
Total Cost
$125,768
Indirect Cost
Name
University of Iowa
Department
Pediatrics
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Meyer, Lauritz R; Dexter, Benjamin; Lo, Cecilia et al. (2018) Perinatal SSRI exposure permanently alters cerebral serotonin receptor mRNA in mice but does not impact adult behaviors. J Matern Fetal Neonatal Med 31:1393-1401
Haskell, Sarah E; Peotta, Veronica; Reinking, Benjamin E et al. (2016) Oral oestrogen reverses ovariectomy-induced morning surge hypertension in growth-restricted mice. Clin Sci (Lond) 130:613-23
Meyer, Lauritz R; Zhu, Vivian; Miller, Alise et al. (2014) Growth restriction, leptin, and the programming of adult behavior in mice. Behav Brain Res 275:131-5
Dexter, Benjamin C; Rahmouni, Kamal; Cushman, Taylor et al. (2014) Neonatal leptin deficiency reduces frontal cortex volumes and programs adult hyperactivity in mice. Behav Brain Res 263:115-21
Roghair, Robert D; Volk, Kenneth A; Lamb, Fred S et al. (2012) Impact of maternal dexamethasone on coronary PGE(2) production and prostaglandin-dependent coronary reactivity. Am J Physiol Regul Integr Comp Physiol 303:R513-9
Roghair, Robert D; Wemmie, John A; Volk, Kenneth A et al. (2011) Maternal antioxidant blocks programmed cardiovascular and behavioural stress responses in adult mice. Clin Sci (Lond) 121:427-36
Hermann, Gregory M; Dallas, Lindsay M; Haskell, Sarah E et al. (2010) Neonatal macrosomia is an independent risk factor for adult metabolic syndrome. Neonatology 98:238-44
Volk, Kenneth A; Roghair, Robert D; Jung, Felicia et al. (2010) Coronary endothelial function and vascular smooth muscle proliferation are programmed by early-gestation dexamethasone exposure in sheep. Am J Physiol Regul Integr Comp Physiol 298:R1607-14
Roghair, Robert D; Segar, Jeffrey L; Volk, Kenneth A et al. (2009) Vascular nitric oxide and superoxide anion contribute to sex-specific programmed cardiovascular physiology in mice. Am J Physiol Regul Integr Comp Physiol 296:R651-62
Hermann, Gregory M; Miller, Rachel L; Erkonen, Gwen E et al. (2009) Neonatal catch up growth increases diabetes susceptibility but improves behavioral and cardiovascular outcomes of low birth weight male mice. Pediatr Res 66:53-8

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