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Assistant Professor |
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The primary objective of this laboratory is to explore, in vivo and in vitro, molecular and cellular mechanisms underlying the regulation of Angiotensin II in the rostral ventrolateral medullar (RVLM) of brainstem and the intermediolateral column (IML) of spinal cord on cardiovascular activity and sympathetic outflow in normal and chronic heart failure (CHF) states. It is believed that the presympathetic neurons (PSNs) in the RVLM directly involve, and therefore play a crucial role, in the regulation of sympathetic outflow via a monosynaptic projection to the sympathetic preganglionic neurons (SPNs) in the IML of spinal cord. These neurons in both RVLM and IML, on the other hand, also are important in the integration and regulation of cardiovascular function and sympathetic activity by receiving input from the neurons in other brain areas or from the interneurons locally in the RVLM and IML. Various neurotransmitters and neuromodulator also play a critical role in these operations, of which Angiotensin II is our focus. The sympatho-excitation in the CHF state is closely related to disorders of the above neuronal processes in the RVLM and the IML. To clarify these mechanisms we are employing real-time RT-PCR and Western blot analysis to determine gene and protein expression of AT1R, AT2R, NOS, and NAD(P)H oxidase in RVLM and IML; gene transfer of AT2R virus and plasmid vehicles into RVLM an IML to study this receptor function and its crosstalk with AT1R; whole cell patch clamp to measure potassium channels of neuronal cells under different interventions; extracellular single unit recording of RVLM and IML to observe the neuronal activity in a rat model; and measurement of arterial blood pressure, heart rate, and renal sympathetic nerve activity to monitor cardiovascular function and sympathetic outflow. These studies are providing novel insights regarding mechanisms of sympatho-excitation in the CHF state from the molecular and genetic level, cellular electrical activity, up to whole animal physiology and pathophysiology. |
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Recent Publications: 1. Haack KK, Gao L, Schiller AM, Curry PL, Pellegrino PR, Zucker IH. Central Rho Kinase Inhibition Restores Baroreflex Sensitivity and Angiotensin II Type 1 Receptor Protein Imbalance in Conscious Rabbits With Chronic Heart Failure. Hypertension. 2013 Jan 2. [Epub ahead of print]. PMID: 23283363. 2. Yu L, Shao C, Gao L. Developmental expression patterns for angiotensin receptors in mouse skin and brain. J Renin Angiotensin Aldosterone Syst. 2012 Nov 30. [Epub ahead of print]. PMID: 23204186. 3. Gao J, Chao J, Parbhu KJ, Yu L, Xiao L, Gao F, Gao L. Ontogeny of angiotensin type 2 and type 1 receptor expression in mice. J Renin Angiotensin Aldosterone Syst. 2012 Sep;13(3):341-52. PMID: 22526820. 4. Fahim M, Gao L, Mousa TM, Liu D, Cornish KG, Zucker IH. Abnormal baroreflex function is dissociated from central angiotensin II receptor expression in chronic heart failure. Shock. 2012 Mar;37(3):319-24. PMID: 22258229. 5. Gao J, Zhang H, Le KD, Chao J, Gao L. Activation of central angiotensin type 2 receptors suppresses norepinephrine excretion and blood pressure in conscious rats. Am J Hypertens. 2011 Jun;24(6):724-30. PMID: 21394088. |
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Erika I. Boesen
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Pamela K. Carmines
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Kurtis G. Cornish
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Lie Gao
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Matthew Kelso
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Shelby Kutty
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Pascale H. Lane
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Yulong Li
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Babu Padanilam
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Kaushik P. Patel
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Iraklis I. Pipinos
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Shyamal K. Roy
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George J. Rozanski
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Steven C. Sansom
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Harold D. Schultz
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Neeru Sharma
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Carol B. Toris
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Saraswathi Viswanathan
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Hanjun Wang
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Hong Zheng
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Matthew C. Zimmerman
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Irving H. Zucker
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