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Neuroscience PhD at Wake Forest University at Wake Forest University


Wake Forest University Graduate School » Neuroscience PhD at Wake Forest University

Debra Diz

Debra Diz
My research covers a wide spectrum of diseases/conditions (hypertension and metabolic syndrome in aging, fetal programming of adult cardiovascular disease) where impairments of vagal function and poor baroreflex function and heart rate variability are risk factors for stroke, cardiac and renal injury.  However, the main focus is on regulation of autonomic function by the renin-angiotensin system at brain sites known to influence the sympathetic and parasympathetic nervous systems. Whole animal integrative physiology and pharmacology,  neuroscience techniques in isolated tissue, and techniques in neuropharmacology and neurophysiology are used to investigate brain areas, transmitters and receptors involved in control of blood pressure. A common thread is that imbalances in angiotensin peptides may influence kinases and phosphatase in the brainstem to account for impairments in autonomic function.   Translation of research to patients is a focus and we use magnetic resonance spectroscopy (MRS) for neurotransmitters as predictors of autonomic function in humans as well as in rats.  Collaborations with clinical and basic scientists in different departments and programs provide many opportunities for trainees.

 

1.  Hypertension and metabolic syndrome in aging.  The brain mechanisms for impairments of vagal function, poor baroreflex function and heart rate variability,  that accompany elevations in blood pressure or impairments in metabolism are studied in transgenic rats with alterations in the brain renin-angiotensin system.  We focus on the role of kinases and phosphatase in the brainstem and the interactions with oxidative stress pathways that may account for impairments in autonomic function.     2. Fetal programming of adult cardiovascular disease.  Changes in components of the brain renin-angiotensin system in sheep exposed prenatally to glucocorticoids are studied as they relate to regulation of autonomic function. 3. Brain transmitters and autonomic function.  We use magnetic resonance spectroscopy (MRS) to measure neurotransmitters as predictors of autonomic function in humans as well as in rats at brain sites known to influence the sympathetic and parasympathetic nervous systems.

 

Arnold AC, Diz DI. Aging is associated with resistance to the cardiovascular actions of leptin for baroreflex modulation [abstract]. FASEB J. 2010; 24(1 Meeting Abstracts):624.8. Logan E, Johnson A, Diz D, Aileru A. Pressor and baroreflex effects of ouabain in (mRen2)27 and mRen2.Lewis rats [abstract]. FASEB J. 2010; 24(1 Meeting Abstracts):977.5. Dhaunsi GS, Yousif MHM, Akhtar S, Chappell MC, Diz DI, Benter IF. Angiotensin-(1-7) prevents diabetes-induced attenuation in PPAR-gamma and catalase activities. Eur J Pharmacol. 2010; 638(1-3):108-114. Arnold AC, Isa K, Shaltout HA, Nautiyal M, Ferrario CM, Chappell MC, Diz DI. Angiotensin-(1-12) requires angiotensin converting enzyme and AT1 receptors for cardiovascular actions within the solitary tract nucleus. Am J Physiol Heart Circ Physiol. 2010; 299(3):H763-H771. Arter A, Nautiyal M, Shaltout H, Chappell M, Diz D. Mas and AT1 receptor expression in adult sheep dorsomedial medulla [abstract]. FASEB J. 2010; 24(1 Meeting Abstracts):625.5. Robbins ME, Zhao W, Garcia-Espinosa MA Diz DI. Renin-angiotensin system blockers and modulation of radiation-induced brain injury. Curr Drug Targets. 2010; 11(11):1413-1422. Garcia-Espinosa MA, Shaltout HA, Olson J, Westwood BM, Robbins ME, Link K, Diz DI. Proton magnetic resonance spectroscopy detection of neurotransmitters in dorsomedial medulla correlate with spontaneous baroreceptor reflex function. Hypertension. 2010; 55(2 Pt 2):487-493. Gwathmey TM, Pendergrass KD, Reid SD, Rose JC, Diz DI, Chappell MC. Angiotensin-(1-7)-angiotensin-converting enzyme 2 attenuates reactive oxygen species formation to angiotensin II within the cell nucleus. Hypertension. 2010; 55(1):166-171. Westwood B, Gwathmey T, Shaltout H, Diz D, Rose J, Chappell M. Immunocytochemical distribution of the Ang-(1-7)/mas receptor in the sheep kidney [abstract]. FASEB J. 2010; 24(1 Meeting Abstracts):605.6. Shaltout HA, Rose JC, Chappell MC, Diz DI. Modulation of baroreflex sensitivity by endogenous angiotensins in lamb solitary tract nucleus [abstract]. FASEB J. 2010; 24(1 Meeting Abstracts):624.7. Shaltout HA, Rose JC, Figueroa JP, Chappell MC, Diz DI, Averill DB. Acute AT1-receptor blockade reverses the hemodynamic and baroreflex impairment in adult sheep exposed to antenatal betamethasone. Am J Physiol Heart Circ Physiol. 2010; 299(2):H541-H547. Nautiyal M, Tallant EA, Chappell MC, Diz DI. Mitogen-activated protein kinase phosphatase-1 (MKP-1) is low in dorsal medulla of hypertensive (mRen2)27 transgenic rats [abstract]. FASEB J. 2010; 24(1 Meeting Abstracts):955.11. Shaltout HA, Figueroa JP, Rose JC, Diz DI, Chappell MC. Alterations in circulatory and renal angiotensin-converting enzyme and angiotensin-converting enzyme 2 in fetal programmed hypertension. Hypertension. 2009; 53(2):404-408. Garcia-Espinosa MA, Shaltout HA, Olson J, Link K, Diz DI. In vivo proton magnetic resonance spectroscopy detection of neurotransmitter/metabolite concentrations in dorsomedial medulla as a noninvasive predictor of autonomic function [abstract]. Hypertension. 2009; 54(4):e48. Arnold AC, Shaltout HA, Gallagher PE, Diz DI. Leptin impairs cardiovagal baroreflex function at the level of the solitary tract nucleus. Hypertension. 2009; 54(5):1001-1008. Isa K, Arnold AC, Chappell MC, Diz DI. Angiotensin-converting enzyme inhibition, but not AT1 receptor blockade, in the solitary tract nucleus improves baroreflex sensitivity in anesthetized transgenic hypertensive (mRen2)27 rats [abstract]. Hypertension. 2009; 54(4):e98. Arnold AC, Diz DI. Baroreflex sensitivity is impaired in Sprague-Dawley rats with spontaneous hydronephrosis independent of angiotensin II actions in the solitary tract nucleus [abstract]. FASEB J. 2009; 23(1 Meeting Abstracts):957.8. Isa K, Garcia-Espinosa MA, Arnold AC, Pirro NT, Tommasi EN, Ganten D, Chappell MC, Ferrario CM, Diz DI. Chronic immunoneutralization of brain angiotensin-(1-12) lowers blood pressure in transgenic (mRen2)27 hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2009; 297(1):R111-115. Awumey EM, Bridges LS, Diz DI. Endothelial nitric oxide synthase knockout and nitric oxide inhibition attenuate Ca2+-induced relaxation of isolated precontracted mouse mesenteric arteries [abstract]. Hypertension. 2009; 54(4):e123. Gwathmey TM, Pendergrass KD, Shaltout HA, Reid SD, Rose JC, Diz DI, Chappell MC. Steroid-induced fetal programming differentially alters nuclear angiotensin II receptor expression and function [abstract]. Hypertension. 2009; 54(4):e42. Pulgar VM, Hong JK, Jessup JA, Massmann AG, Diz DI, Figueroa JP. Mild chronic hypoxemia modifies expression of brain stem angiotensin peptide receptors and reflex responses in fetal sheep. Am J Physiol Regul Integr Comp Physiol. 2009; 297(2):R446-R452. Logan EM, Johnson A, Diz DI, Aileru A. Nicotinic and AT1 receptors show enhanced responsiveness in the superior cervical ganglia of (mRen2)27 versus Sprague-Dawley rats [abstract]. Hypertension. 2009; 54(4):e85-e86. Shaltout HA, Diz DI, Figueroa JP, Chappell MC, Rose JC. Sympathetic nervous system mediated responses to behavioral or pharmacologic challenges are exaggerated as a result of antenatal betamethasone exposure [abstract]. Hypertension. 2009; 54(4):e101`. Anton L, Merrill DC, Neves LAA, Diz DI, Corthorn J, Stovall K, Gallagher PE, Moorefield C, Gruver C, Brosnihan KB, et al. The uterine placental bed renin-angiotensin system in normal and preeclamptic pregnancy. Endocrinology. 2009; 150(9):4316-4325. Gilliam-Davis S, Tommasi EN, Garcia-Espinosa MA, Chappell MC, Brosnihan KB, Diz DI. Bilateral renal denervation prevents age-related proteinuria without altering excretion of intrarenal angiotensin peptides in Sprague-Dawley rats [abstract]. Hypertension. 2009; 54(4):e76. Gwathmey TM, Pendergrass KD, Rose JC, Diz DI, Chappell MC. Nuclear angiotensin-(1-7) receptors mediate the production of nitric oxide [abstract]. Hypertension. 2009; 54(4):e74. Shaltout HA, Figueroa JP, Rose JC, Chappell MC, Averill DB, Diz DI. Antenatal betamethasone causes alterations in angiotensin receptors in sheep brain in a gender specific manner [abstract]. FASEB J. 2009; 23(1 Meeting Abstracts):941.11. Robbins ME, Payne V, Tommasi E, Diz DI, Hsu F-C, Brown WR, Wheeler KT, Olson J, Zhao W. The AT1 receptor antagonist, L-158,809, prevents or ameliorates fractionated whole-brain irradiation-induced cognitive impairment. Int J Radiat Oncol Biol Phys. 2009; 73(2):499-505. Al-Maghrebi M, Benter IF, Diz DI. Endogenous angiotensin-(1-7) reduces cardiac ischemia-induced dysfunction in diabetic hypertensive rats. Pharmacol Res. 2009; 59(4):263-268. Gwathmey TM, Shaltout HA, Pendergrass KD, Pirro NT, Figueroa JP, Rose JC, Diz DI, Chappell MC. Nuclear angiotensin II type 2 (AT2) receptors are functionally linked to nitric oxide production. Am J Physiol Renal Physiol. 2009; 296(6):F1484-1493. Arnold AC, Shaltout HA, Gallagher PE, Diz DI. Protein phosphatase 1b activity in the solitary tract nucleus is necessary for normal baroreflex function [abstract]. Hypertension. 2009; 54(4):e100. Anton L, Merrill DC, Neves LAA, Stovall K, Gallagher PE, Diz DI, Moorefield C, Gruver C, Ferrario CM, Brosnihan KB. Activation of local chorionic villi angiotensin II levels but not angiotensin (1-7) in preelampsia. Hypertension. 2008; 51(4):1066-1072. Arnold AC, Sakima A, Ganten D, Ferrario CM, Diz DI. Modulation of reflex function by endogenous angiotensins in older transgenic rats with low glial angiotensinogen. Hypertension. 2008; 51(5):1326-1331. Arnold AC, Shaltout HA, Gallagher PE, Ganten D, Ferrario CM, Diz DI. Leptin impairs baroreflex sensitivity at the solitary tract nucleus: evidence for upregulation of leptin actions in animals with low brain angiotensinogen [abstract]. Hypertension. 2008; 52(4):e50. Logan EM, Diz DI, Ferrario CM, Ganten D, Aileru AA. Differences in ganglionic transmission between (mRen)27 and mRen2.Lewis models of hypertension [abstract]. Hypertension. 2008; 52(4):e65. Diz DI. Future directions in cardiovascular pharmacology: examples from the renin-angiotensin system. Mol Interv. 2008; 8(5):222-225. Robbins M, Payne V, Diz D, Hsu FC, Zhao WL. Chronic inhibition of the renin-angiotensin system prevents radiation-induced cognitive impairment in the adult male rat [abstract]. Neuro Oncol. 2008; 10(5):851. Diz DI, Garcia-Espinosa MA, Gegick S, Tommasi EN, Ferrario CM, Tallant EA, Chappell MC, Gallagher PE. Injections of angiotensin-converting enzyme 2 inhibitor MLN4760 into nucleus tractus solitarii reduce baroreceptor reflex sensitivity for heart rate control in rats. Exp Physiol. 2008; 93(5):694-700. Diz DI. Lewis K. Dahl memorial lecture: the renin-angiotensin system and aging. Hypertension. 2008; 52(1):37-43. Garcia-Espinosa MA, Shaltout HA, Chappell MC, Gallagher PE, Ferrario CM, Ganten D, Reudelhuber TL, Diz DI. Angiotensin-(1-7) replacement gene transfer in the cisterna magna lowers blood pressure and improves baroreflex function in transgenic (mRen2)27 rats [abstract]. Hypertension. 2008; 52(4):e36. Benter IF, Yousif MHM, Dhaunsi GS, Kaur J, Chappell MC, Diz DI. Angiotensin-(1-7) prevents activation of NADPH oxidase and renal vascular dysfunction in diabetic hypertensive rats. Am J Nephrol. 2008; 28(1):25-33. Gilliam-Davis S, Gallagher PE, Payne VS, Kasper SO, Tommasi EN, Robbins ME, Diz DI. Long-term systemic renin-angiotensin system blockade alters expression of renin-angiotensin system components in dorsomedial medulla of Fischer 344 rats [abstract]. Hypertension. 2008; 52(4):e61. Isa K, Garcia-Espinosa MA, Arnold AC, Pirro NT, Tommasi EN, Ferrario CM, Chappell MC, Diz DI. Angiotensin-(1-12) contributes to renin-independent angiotensin II activity in brain [abstract]. Hypertension. 2008; 52(4):e81. Diz DI, Varagic J, Groban L. Aging and the brain renin-angiotensin system: relevance to age-related decline in cardiac function. Future Cardiol. 2008; 4(3):237-245. Awumey EM, Bridges LS, Diz DI. Inhibition of phospholipase A2 and K-Ca channels attenuates calcium-induced relaxation of isolated, phenylephrine-contracted rat mesenteric arteries [abstract]. Hypertension. 2008; 52(4):e117. Anton L, Merrill DC, Diz D, Neves LA, Gallagher PE, Stovall K, Moorefield C, Gruver C, Ferrario CM, Brosnihan KB. Elevation of maternal uterine placental bed angiotensin II levels is associated with increased renin and ACE mRNA in preeclampsia [abstract]. Hypertension. 2008; 52(4):e49. Pulgar V, Diz D, Hong JK, Figueroa JP. Chronic mild hypoxemia during late gestation decreases baroreceptor gain in fetal sheep [abstract]. Reprod Sci. 2008; 15(2 Suppl):129A. Diz DI, Garcia-Espinosa MA, Gallagher PE, Ganten D, Ferrario CM, Averill DB. Angiotensin-(1-7) and baroreflex function in nucleus tractus solitarii of (mRen2)27 transgenic rats. J Cardiovasc Pharmacol. 2008; 51(6):542-548. Shaltout HA, Figueroa JP, Rose JC, Diz DI, Chappell MC. Reduced renal ACE2 in fetal programmed hypertension [abstract]. Hypertension. 2008; 52(4):e52. Awumey EM, Hill SK, Diz DI, Bukoski RD. Cytochrome P-450 metabolites of 2-arachidonoylglycerol play a role in Ca2+-induced relaxation of rat mesenteric arteries. Am J Physiol Heart Circ Physiol. 2008; 294(5):H2363-2370. Logan EM, Diz DI, Ferrario CM, Ganten D, Averill DB. Inhibition of the PI3 kinase pathway in the nTS of hypertensive rats improves baroreceptor reflex sensitivity [abstract]. Hypertension. 2008; 52(4):e80. Shaltout HA, Figueroa JP, Rose JC, Chappell MC, Averill DB, Diz DI. Evidence of Ang-(1-7) deficiency in antenatal betamethasone-treated young adult sheep [abstract]. Hypertension. 2008; 52(4):e107. Sakima A, Averill DB, Kasper SO, Jackson L, Ganten D, Ferrario CM, Gallagher PE, Diz DI. Baroreceptor reflex regulation in anesthetized transgenic rats with low glia-derived angiotensinogen. Am J Physiol Heart Circ Physiol. 2007; 292(3):H1412-1419. Gilliam-Davis S, Chappell MC, Diz DI. Elevated angiotensin I and creatinine excretion precede the increase in proteinuria during aging in Sprague-Dawley rats [abstract]. Hypertension. 2007; 50(4):e121. Logan EM, Ferrario CM, Diz DI, Averill DB. The PI3 kinase signal transduction pathway in nucleus tractus solitarii participates in maintenance of resting arterial [abstract]. Hypertension. 2007; 50(4):e116. Sesay JS, Diz DI, Howlett AC, Awumey EM. Ca2+-sensing receptor signaling in mouse neuroblastoma cells: a model for the perivascular sensory nerve Ca2+-sensing receptor [abstract]. Hypertension. 2007; 50(4):e124. Shaltout HA, Figueroa JP, Rose JC, Chappell MC, Averill DB, Diz DI. Gender differences in the development of insulin resistance in adult sheep as result of antenatal betamethasone [abstract]. FASEB J. 2007; 21(5 Pt I):A434. Zhao W, Diz DI, Robbins ME. Oxidative damage pathways in relation to normal tissue injury. Br J Radiol. 2007; 80(Special Issue 1):S23-S31. Gwathmey TM, Diz DI, Pirro NT, Figueroa J, Rose JC, Chappell MC. Nuclear angiotensin II-type 2 receptors are differentially expressed in the sheep kidney [abstract]. Hypertension. 2007; 50(4):e97. Yousif MH, Benter IF, Diz DI, Chappell MC. Evidence that multiple receptor subtypes mediate angiotensin-(1-7) dependent vasodilation of the rat renal artery [abstract]. Hypertension. 2007; 50(4):e154-e155. Anton L, Merrill DC, Diz DI, Neves LA, Stovall K, Gallagher PE, Moorefield C, Gruver C, Ferrario CM, Brosnihan KB. The increased shift of the Ang II/Ang-(1-7) balance in the chorionic villi from preeclamptic subjects is mediated by the AT1 receptor [abstract]. Hypertension. 2007; 50(4):e79. Diz DI, Kasper SO, Sakima A, Ferrario CM. Aging and the brain renin-angiotensin system: insights from studies in transgenic rats. Cleve Clin J Med. 2007; 74(Suppl 1):S95-S98. Benter IF, Yousif MHM, Cojocel C, Al-Maghrebi M, Diz DI. Angiotensin-(1-7) prevents diabetes-induced cardiovascular dysfunction. Am J Physiol Heart Circ Physiol. 2007; 292(1):H666-H672. Arnold AC, Sakima A, Ganten D, Ferrario CM, Diz DI. Ang II and Ang-(1-7) in the solitary tract nucleus participate in the anesthesia-induced elevation of mean arterial pressure in older rats with low glial angiotensinogen [abstract]. Hypertension. 2007; 50(4):e116. Ferrario CM, Averill DB, Brosnihan KB, Chappell MC, Diz DI, Gallagher PE, Neves L, Tallant EA. Regulation of cardiovascular control mechanisms by angiotensin (1-7) and angiotensin-converting enzyme 2. In: Carey RM, ed. Hypertension and hormone mechanisms. Totowa (NJ): Humana Press; 2007: 43-59. Zhao W, Payne V, Tommasi E, Diz DI, Hsu F-C, Robbins ME. Administration of the peroxisomal proliferator-activated receptor gamma agonist pioglitazone during fractionated brain irradiation prevents radiation-induced cognitive impairment. Int J Radiat Oncol Biol Phys. 2007; 67(1):6-9. Arnold AC, Sakima A, Ganten D, Ferrario CM, Diz DI. Baroreceptor reflex regulation in anesthetized older transgenic rats with low brain angiotensinogen: role of endogenous angiotensin II and angiotensin-(1-7) [abstract]. FASEB J. 2007; 21(6 Pt II):A889. Awumey EM, Howlett AC, Putney JW Jr, Diz DI, Bukoski RD. Ca2+ mobilization through dorsal root ganglion Ca2+-sensing receptor stably expressed in HEK293 cells. Am J Physiol Cell Physiol. 2007; 292(5):C1895-1905. Shaltout HA, Westwood BM, Averill DB, Ferrario CM, Figueroa JP, Diz DI, Rose JC, Chappell MC. Angiotensin metabolism in renal proximal tubules, urine and serum of sheep: evidence for ACE2-dependent processing of angiotensin II. Am J Physiol Renal Physiol. 2007; 292(1):F82-F91. Gilliam-Davis S, Payne VS, Kasper SO, Tommasi EN, Robbins ME, Diz DI. Long-term AT1 receptor blockade improves metabolic function and provides renoprotection in Fischer-344 rats. Am J Physiol Heart Circ Physiol. 2007; 293(3):H1327-33. Groban L, Ferrario CM, Ganten D, Diz DI. Transgenic rats with low brain renin-angiotensin system activity due to glial deficiency are protected against heart failure late in life [abstract]. J Card Fail. 2007; 13(6 Suppl 2):S83. Kasper SO, Ferrario CM, Ganten D, Diz DI. Rats with low brain angiotensinogen do not exhibit insulin resistance during early aging. Endocrine. 2006; 30(2):167-174. Sakima A, Averill DB, Kasper SO, Tommasi E, Gilliam-Davis S, Jackson L, Ganten D, Ferrario CM, Diz D. Cardiovascular and autonomic control in transgenic rats with low glial-derived angiotensinogen [abstract]. J Hypertens. 2006; 24(Suppl 6):157. Somasundaram C, Bukoski RD, Diz DI. Presence of growth-associated protein 43 and calcium sensing receptor in adventitial neuronal somata (ANNIES) and perivascular nerves of the adult rat mesenteric branch artery [abstract]. Hypertension. 2006; 48(4):e71-e72. Garcia-Espinosa MA, Vinsant S, Gallagher PE, Ferrario CM, Ganten D, Chappell MC, Diz DI. Regulation of brain neprilysin and ACE2 in transgenic rats during aging [abstract]. Am J Med Sci. 2006; 331(2):61. Awumey EM, Diz DI, Howlett AC, Putney JW Jr. Downregulation of protein kinase C inhibits perivascular sensory nerve Ca2+-sensing receptor signaling [abstract]. Hypertension. 2006; 48(4):e85-e86. Benter IF, Yousif MH, Cojocel C, Al-Maghrebi M, Diz DI. Renal dysfunction in diabetic SHR is attenuated by treatment with angiotensin-(1-7) [abstract]. Hypertension. 2006; 48(4):e101. Diz DI, Tommasi EN, Ferrario CM, Tallant EA, Gallagher PE. ACE2 inhibition in the nucleus of the solitary tract reduces baroreceptor reflex sensitivity [abstract]. Hypertension. 2006; 48(4):e87. Shaltout HA, Figueroa JP, Rose JC, Chappell MC, Diz DI, Averill DB. Antenatal betamethasone causes angiotensin II-mediated impairment of baroreflex control of heart rate [abstract]. J Hypertens. 2006; 24(Suppl 6):159. Shaltout HA, Figueroa JP, Rose JC, Averill DB, Diz DI, Chappell MC. Increased blood pressure is associated with lower serum ACE2 activity and higher ACE activity following antenatal steroid exposure [abstract]. J Hypertens. 2006; 24(Suppl 6):127. Robbins ME, Diz DI. Pathogenic role of the renin-angiotensin system in modulating radiation-induced late effects. Int J Radiat Oncol Biol Phys. 2006; 64(1):6-12. Shaltout HA, Figueroa JP, Rose JC, Chappell M, Diz DI, Averill DB. Antenatal betamethasone causes angiotensin II-mediated impairment of cardiovascular function [abstract]. Hypertension. 2006; 48(4):e32. Garcia-Espinosa MA, Gallagher PE, Ganten D, Ferrario CM, Reudlehuber TL, Diz DI. Intracisternal injection of angiotensin-(1-7)-producing fusion protein plasmid lowers blood pressure in hypertensive (mRen2)27 rats [abstract]. Hypertension. 2006; 48(4):e87. Kasper SO, Sakima A, Ferrario CM, Ganten D, Diz DI. Altered stress responses in rats with low glial angiotensinogen [abstract]. Am J Med Sci. 2006; 331(2):63.