Dr. Wang's Laboratory

Dr. Wang’s laboratory has been generally interested in the roles of the somatic/visceral sensory nervous system in both cardiovascular and neuropathic pain diseases. Particular interests in this lab have been primarily, but not limited to, the role of skeletal muscle afferents and cardiopulmonary spinal afferents in experimental chronic heart failure (CHF). Another important research direction of this laboratory is to explore the novel roles of skeletal muscle afferents in mediating “walking pain” in peripheral arterial diseases.

In the past, this laboratory conducted both integrative physiological experiments such as in vivo single fiber recording and in vitro patch clamp in DRG neurons to characterize the abnormalities in somatic/visceral sensory afferents in cardiovascular diseases. For example, the studies from this laboratory discovered that chemical cardiac sympathetic afferent desensitization with the drug resiniferatoxin (RTX) reduces cardiac fibrosis, inflammation, and apoptosis and improves cardiac diastolic dysfunction in post-myocardial infarction rats, indicating a novel therapeutic concept for the treatment of CHF. A US patent related to this finding had been issued (No.9956166). These studies are also ongoing as part of two NIH RO1 grants (HL126796-01A1 and HL 121012-01A1) that are exploring the roles of cardiac and skeletal muscle afferents in cardiovascular diseases.



 Juan Hong, PhD
Post-Doctoral Fellow

Zhiqiu (Claire) Xia
Graduate Student Research Assistant


#1: Skeletal Muscle Afferents in Healthy and Diseases (CHF and PAD).

Exercise evokes sympathetic activation and increases blood pressure and heart rate. Two neural mechanisms that cause the exercise-induced increase in sympathetic discharge are central command and the exercise pressor reflex (EPR). The former suggests that a volitional signal emanating from central motor areas leads to increased sympathetic activation during exercise. The latter is a peripheral neural reflex originating in skeletal muscle which contributes significantly to the regulation of the cardiovascular and respiratory systems during exercise. In heart failure, the sympathetic activation during exercise is exaggerated, which potentially increases cardiovascular risk and contributes to exercise intolerance during physical activity in chronic heart failure (CHF) patients.

Our work focuses primarily on the neural control mechanisms underlying the exaggerated cardiovascular response and hyperventilation during exercise in the CHF state. We recently provided the direct evidence demonstrating that muscle mechanically sensitive afferents (Group III) are sensitized in a CHF rat model whereas the metabolically sensitive afferents (group IV) are desensitized. Currently, our study is looking for the cellular and molecular mechanisms underlying the abnormal sensitization of muscle afferents in CHF with the integrative techniques such as patch clamp, single fiber recording and common molecular techniques (western blot, PCR, immunohistochemistry and in vivo or in vitro gene transfer). In addition, we recently found that besides muscle afferents, spinal cord dysfunction may also contribute to the exaggerated cardiovascular response during exercise in CHF. The imbalance between glutamatergic and GABAergic input in the spinal cord may cause the enhanced spinal neuronal excitability in CHF. Finally, based on our previous finding that long-term exercise training (ExT), as a non-pharmacological therapeutic strategy, prevents the progression of the exaggerated EPR in CHF. We are focusing on the underlying mechanisms.

Research Interest #2: Cardiac Sympathetic Afferent Ablation in Heart Failure.

In a recently published paper in Hypertension (2014; 64(4):745-55) we identified a novel role of the cardiac sympathetic afferent reflex (CSAR) in mediating cardiac structural and functional remodeling following myocardial infarction. Most importantly in that study, we demonstrated a novel therapeutic concept for the treatment of CHF through chemical cardiac sympathetic afferent desensitization with the drug resiniferatoxin. This is a highly novel finding with significant clinical application. We furthermore demonstrated that this novel therapeutic strategy largely prevented the deleterious cardiac remodeling process and greatly improved cardiac diastolic dysfunction in CHF animals. In a more recent paper in the Journal of Physiology (2017;595(8):2519-34.), we further discovered the detailed mechanisms how CSAR controls cardiac function in normal and CHF states. Our data, for the first time to our knowledge, suggest that there is an unbalance between cardiac and peripheral responses to CSAR in CHF animals. In the normal state, activation of the CSAR causes a potent increase in cardiac contractility with a moderate increase in peripheral vasoconstriction, whereas it causes very little increase in cardiac contractility with an exaggerated peripheral vasoconstriction in the CHF state. The former results in increased cardiac output with decreased cardiac diastolic and systolic volumes, whereas the latter causes a small increase in cardiac output associated with increased cardiac systolic and diastolic volumes and LVEDP.

  In ongoing studies, we are exploring an alternative route of epidural peri-ganglion administration of RTX for CSAR ablation thus destroying TRPV1-expressing CSAR afferent neuronal soma at the level of the T1-T4 DRG in post-MI rats. These studies have very high translational potential and could have a large impact on the current clinical therapeutic strategy for heart failure. A US patent has been granted related to all these findings above (United States Patent No. 9956166).


  1. Shanks J, Xia Z, Lisco SJ, Rozanski GJ, Schultz HD, Zucker IH, Wang HJ. Sympatho-Excitatory Response to Pulmonary Chemosensitive Spinal Afferent Acitivation in Anesthetized, Vagotomized Rats. Physiol Rep. 2018 (In Press).
  2. Wang HJ, Rozanski GJ, Zucker IH. Cardiac Sympathetic Afferent Reflex Control of Cardiac Function in Normal and Chronic Heart Failure States. J Physiol. 2017;595(8):2519-2534.
  3. Becker BK, Tian C, Zucker IH, Wang HJ. Influence of brain-derived neurotrophic factor-TrkB signaling in the NTS on baroreflex sensitivity in rats with chronic heart failure. J Physiol. 2016;594(19):5711-25.
  4. Wang HJ, Cahoon R, Cahoon EB, Zheng H, Patel KP, Zucker IH.  Glutamatergic receptor dysfunction in spinal cord contributes to the exaggerated exercise pressor reflex in heart failure. Am J Physiol Heart Circ Physiol. 2015 Mar 1; 308(5):H447-55. Wang HJ, Wang W, Cornish KG, Rozanski GJ, Zucker IH.  Cardiac sympathetic afferent denervation attenuates cardiac remodeling and improves cardiovascular dysfunction in rats with heart failure.  Hypertension. 2014 Oct; 64(4):745-55.