Cellular & Integrative Physiology

• NAME/TRAINING:

Back to Top

ACADEMIC DEGREES:

B.S., Biology, City College of New York; M.S.,
Biology, University of Missouri at Kansas City; Ph.D., New
York Medical College, NYC, NY

Back to Top

• CONTACT INFORMATION:

Phone Number:	402-559-7161
e-mail addresses:	izucker@unmc.edu

Back to Top

PO1 HL0622205 (Zucker)	07-01-2004 – 06-30-2009
National Institutes of Health Neuro-Circulatory Function in Chronic Heart Failure Project I: Sympathetic Outflow in Heart Failure:  AII and NO (Zucker) Project II:  Function of the PVN in Heart Failure:   Role of NO and GABA – (K.P. Patel) Administration Core – (I.H. Zucker) The aim of the program project grant is to understand the central interaction between various neurohumoral substances and the regulation of sympathetic nerve activity in animal models of chronic heart failure (CHF).  Experiments are carried out in three projects and three cores.  These studies evaluate baroreflex, chemoreflex and cardiopulmonary reflexes, the roles of angiotensin II and nitric oxide on the sympatho-excitatory process in CHF. Role:  Program Director and Principal Investigator
No Number Available (Cardiovascular Therapeutics, Inc.)	02-01-2008 - 01-31-2009
Evaluation of diastolic dysfunction in heart failure following therapy with Ranolazine. This is a trial to look at the late sodium channel inhibitor Ranolazine on diastolic properties of the myocardium in an animal model of chronic heart failure. Role: Principal Investigator

Back to Top

• PUBLICATIONS (last 5 years):

Selected peer-reviewed publications (Selected from 178)
Wang, Y., Patel, K. P., Cornish, K. G., Channon, K. M., and I. H. Zucker. nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure. Am. J. Physiology (Heart and Circulatory Physiology) 285:H1660-H1667, 2003.

Pliquett, R. U., Cornish, K. G. and I. H. Zucker. Statin therapy restores sympathovagal balance in experimental heart failure. J. Appl. Physiology 95:700-704, 2003.

Pliquett, R.U., Cornish, K.G., Peuler, J.D. and I. H. Zucker. Simvastatin normalizes autonomic neural control in experimental heart failure. Circulation 107:2493-2498, 2003.

Gao, L., Wang, W., Li, Y -L., Schultz, H.D., Cornish, K. G., Zucker, I. H. Superoxide Mediates Sympatho-Excitation in Heart Failure: The Roles of Angiotensin II and NAD(P)H Oxidase. Circ. Res., 95:937-944, 2004.

Zhu, G-Q., Gao, L., Li, Y-F., Patel, K. P., Zucker, I. H., Wang, W. AT1 receptor mRNA antisense normalizes the enhanced cardiac sympathetic afferent reflex in rats with chronic heart failure. Am. J. Physiology (Heart and Circulatory Physiology) 287:H1828-H1835, 2004.

Li, Y-L., Sun, S-Y., Overholt, J. L., Prabhakar, N. R., Rozanski, G.J., Zucker, I. H., Schultz, H. D. Attenuated outward potassium currents in carotid body glomus cells of heart failure rabbit: involvement of nitric oxide. J. Physiol. (Lond.) 555:219-229, 2004.

Zhu, G-Q., Gao, L. , Patel, K. P., Zucker, I. H., and W. Wang. Ang II in the paraventricular nucleus potentiates the cardiac sympathetic afferent reflex in rats with heart failure. J. Applied Physiol. 97:1746-1754, 2004.

Gao, L., Zhu, Z., Zucker, I. H., Wang, W. Cardiac sympathetic afferent stimulation impairs baroreflex control of renal sympathetic nerve activity in rats  Am. J. Physiology (Heart and Circulatory Physiology) 286:H1706-H1711, 2004.

Gao, L., Schultz, H.D., Patel, K. P., Zucker, I. H., Wang, W. Augmented input from cardiac sympathetic afferents inhibits baroreflex in rats with heart failure. Hypertension. 45:1180-1188, 2005

Zucker, I. H., Gao, L. The Regulation of Sympathetic Nerve Activity by Angiotensin II Involves Reactive Oxidant Stress and MAPK. Editorial, Circulation Research, 97:737-739, 2005

Mousa,T.M., Gao, L., Cornish, K.G., Zucker, I.H. Effects of angiotensin II on autonomic components of nasopharyngeal stimulation in male conscious rabbits. J. Applied Physiol. 98: 1607-1611, 2005.

Gao L, Wang W, Li YL, Schultz HD, Liu D, Cornish KG, Zucker IH. Sympathoexcitation by central ANG II: roles for AT1 receptor upregulation and NAD(P)H oxidase in RVLM. Am J Physiol Heart Circ Physiol. 288(5):H2271-9; 2005.

Zheng, H., Li, Y-F., Zucker, I. H. and K. P. Patel. Exercise training improves endogenous nitric oxide mechanisms within the paraventricular nucleus in rats with heart failure. Am. J. Physiology (Heart and Circulatory Physiology) 288:H2332-H2341,2005

 Li, Y-L, Li, Y-F., Liu, D., Cornish, K. G., Patel, K. P., Zucker, I. H., Channon, K. M., Schultz, H.D. Gene transfer of nNOS to carotid body reverses enhanced chemoreceptor function in heart failure rabbits. Circulation Research 97:260-267, 2005

Gao, L., Wang, W., Li, Y-L., Schultz, H.D., Liu, D., Cornish, K. G., Zucker, I.H. Simvastatin therapy normalizes sympathetic neural control in experimental heart failure: The roles of AT1 receptors and NAD(P)H Oxidase. Circulation. 112:1763-1770, 2005.

 Wang, Y., Liu, Xue-Fei, Cornish, K. G., Zucker, I. H., Patel, K. P. Effects of nNOS antisense in the paraventricular nucleus on blood pressure and heart rate in rats with heart failure. Am. J. Physiology  (Heart and Circulatory Physiology) 288:H205-H213, 2005                                              

Xie, F., Tsutsui, J. M., Gao, L., Curry, P., Porter, T. R., Zucker, I. H. The Effect of Transthoracic Ultrasound and Intravenous Microbubbles on Sympathetic Nerve Activity in Normal and Heart Failure Rabbits. Ultrasound in Medicine and Biology. (In Press, 2006).

Zheng, H., Li, Y-F., Zucker, I. H., Patel, K. P. Exercise training improves renal excretory responses to acute volume expansion in rats with heart failure. Am. J. Physiol. (Renal Physiology) 291:F1148-F1156, 2006.

Liu, D., Gao, L., Roy, S. K., Cornish, K. G., Zucker, I. H. Neuronal AT1 receptor up –regulation in heart failure: Activation of AP-1 and JNK. Circulation Research 99:1004-1011, 2006.

Wang, W-Z., Gao., L., Pan, Y-X., Zucker, I. H., Wang, W. Differential effects of cardiac sympathetic afferent stimulation on neurons in the nucleus tractus solitarius. Neurosci. Lett. 409:146-150, 2006.

Zucker, I. H. Novel mechanisms of sympathetic regulation in chronic heart failure. Hypertension. 48:1005-1011, 2006.

Xie, F., Tsutsui, J. M., Gao, L., Curry, P., Porter, T. R., Zucker, I. H. The Effect of Transthoracic  Ultrasound and Intravenous Microbubbles on Sympathetic Nerve Activity in Normal and Heart Failure Rabbits. Ultrasound in Medicine and Biology. Ultrasound in Medicine and Biology 33:136-144, 2007.

Gao, L., Wang, W., Liu, D., Zucker, I.H. Exercise training normalizes sympathetic outflow by central antioxidant mechanisms in rabbits with pacing-induced chronic heart failure. Circulation.  115:3095-3102, 2007.

Li, Y-L., Gao, L. , Zucker, I. H., Schultz, H.D. NADPH oxidase-derived superoxide anion mediates angiotensin II-enhanced carotid body chemoreceptor sensitivity in rabbits with chronic heart failure. Cardiovascular Res. 75:546-554, 2007.135.

 

Wang,W-Z., Gao, L., Pan, Y-X., Zucker, I. H., Wang W. AT1 receptors in the nucleus tractus solitarii mediate the interaction between the baroreflex and the cardiac sympathetic afferent reflex in anesthetized rats. Am. J. Physiol. (Regul. Integrat. Comparative Physiology). 292:R1137-R1145, 2007.

 

Zucker, I.H., Hackley, J. F., Cornish, K. G., Hiser, B.A., Anderson, N. R., Kieval, R., Irwin, E.D., Serdar,     D. J., Peuler, J. D., Rossing, M. A. Chronic baroreceptor activation enhances survival in dogs with pacing-induced heart failure. Hypertension 50:904-910, 2007.

 

Gao, L., Wang, W-Z., Wang, W., Li, H., Sumners, C., Zucker, I. H. Effects of AT2 receptor over expression in the RVLM on blood pressure and urine excretion in normal rats. Hypertension 51:1-7, 2008.

 

Mousa, T. M., Liu, D., Cornish, K. G., Zucker, I. H. Exercise training enhances baroreflex sensitivity by an Angiotensin II dependent mechanism in chronic heart failure. J. Appl. Physiol. 104:616-624, 2008.

Liu, D., Gao, L., Roy, S. K., Cornish, K.G., Zucker, I. H. The Role of oxidant stress on AT1 Receptor Expression in Rabbits with Heart Failure and in Cultured Neurons. Circ. Res. (In Press, 2008).

Rajagopalan, V., Zucker, I.H., Jones, J. A., Carlson, M., Ma, Y. J. Cardiac-specific ErbB-1 (EGFR) mutant expression in young adult mice leads to cardiac dysfunction. Am. J. Physiol. Heart and Circulatory Physiology. (In Press, 2008).

Back to Top

• PREVIOUS GRADUATE STUDENTS/POST-DOCTORAL FELLOWS (present location):

John R. Dietz, ’76-’79, Professor, Department of Physiology, University of South Florida, Tampa, Florida.

Mark J. Holmberg, ‘’80-’83, Cardiologist in private practice, Omaha, Nebraska.

Michael A. Hadju, ’84-’88, Medical Resident, University of Vermont.

Wen Tan, ’84-’89, Center for Advanced Medicine & Drug Development, Beijing, China.

Joseph McClain, ’89-’90, Surgical Fellow, San Antonio, Texas

Yu-Wang, 2000-present, Department of Physiology, UNMC, Omaha, Nebraska

Andrew J. Gorman, Ph.D., ’80-’82, Research Scientist, Hoechst-Celanese Corporation, Summerville, New Jersey.

Mark J. Niebauer, M.D., Ph.D.Faculty, Division of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio

Maret J. Panzenbeck, ’85-’88, Research Scientist, beringer-Ingelheim, Connecticut.

Wei Wang, M.D., Ph.D., Associate Professor, Department of Physiology, UNMC, Omaha, Nebraska

Jwo-Sheng Chen, Ph.D., ’88-’90, Chairman, Department of Physiology, China Medical College, Taichung, Taiwan.

Marian Brandle, Ph.D., ’90-’92, Merck & Company, Darmstadt, Germany.

Jun-Li Liu, ’95-’99, Postdoctoral Fellow, Cornell Hospital, New York City, New York

Hiroshi Murakami, M.D., Ph.D., ’94-’96, Assistant Professor, Department of Surgery, Kagawa Medical School, Kagawa, Japan.

Shu-Yu Sun, M.D., Ph.D., ’96-’98, Manager, Cardiovascular Laboratory, Merck & Company, Rahway, New Jersey

Kiyoshi Tsunooka, M.D., Ph.D., ’98-‘2000, Medical Resident, University of Nagoya, Japan.

Rainer Pliquett, M.D., ’00-’01.  Returned to Germany.

Dongmei Liu, Ph.D., 2000-present,  Postdoctoral Fellow, UNMC, Omaha, Nebraska

Tarek Mousa, M.D., 2003-present, Postdoctoral Fellow, UNMC, Omaha, Nebraska

Lie Gao, M.D., Ph.D., 2003-present, Postdoctoral Fellow, UNMC, Omaha, Nebraska

Mohammad Fahim, Ph.D. 2004-present, visiting scientist (sabbatical leave from U. of New Delhi), UNMC, Omaha, NE

        Back to Top

• CURRENT RESEARCH PROJECTS:

The research carried out in this laboratory strives to understand the regulation of sympathetic nervous outflow in chronic heart failure (CHF). The sympatho-excitation which is a characteristic of and prognostic indicator of the CHF state is modulated by peripheral cardiovascular reflexes and circulating as well as central alterations in a variety of humoral agents. Some of these are angiotensin II, nitric oxide, endothelin-1, atrial natriuretic peptide, etc. Techniques involving chronic animal preparations and molecular biology are used to understand the modulation of sympathetic tone and cardiovascular reflex function in the setting of CHF. The integrative function of many of these hormones is evaluated in conscious, chronically instrumented animals with CHF. The role of exercise training on hemodynamic, neural and hormonal regulation of sympathetic tone is evaluated in the CHF state. The mechanisms for up regulation of angiotensin II receptors in cardiovascular control regions of the brain are investigated. The role of oxidative stress in heart failure is a major theme of the laboratory. Finally, several pharmaceutical and device experiments are carried out using models of CHF.

Back to Top

• SPECIALIZED LABORATORY/CLINICAL RESEARCH RESOURCES:

Chronic animal instrumentation including recording of sympathetic nerve activity.

Measurement of hemodynamics including left ventricular and arterial pressure, and cardiac dimensions, echocardiography.

RT-PCR, real time PCR, Western Analysis for nitric oxide synthase, ang II receptors, NAD(P)H Oxidase subunits.

Adeno viral gene transfer of nNOS.

Measurement of reactive oxidant species.

Back to Top