Autonomic Control of Circulation in Health and Cardiovascular Diseases

The global aim of my research effort has been to explore the sympathetic nervous mechanisms that govern control of the circulation in cardiovascular diseases, such as heart failure (HF) and hypertension etc. Specifically, research programs have focused on understanding the central and muscular mechanisms of cardiovascular responses to exercise in those cardiovascular disorders. Our recent work has shown that in HF ATP enhances muscle afferent mediated cardiovascular responses via P2X receptor (Circulation 110: 3049, 2004) and also stimulates this receptor and increase norepinephrine release from the sympathetic nerves in active muscle (Circulation 111: 2748, 2005). The results suggest that the augmented P2X-mediated responsiveness may influence the processing of muscle afferent and sympathetic signals in HF. Work from our lab has also demonstrated that muscle metabolites, i.e. lactate acid and phosphate stimulate acid sensing ion channels (ASIC) and evoke muscle afferent engagement cardiovascular responses. ASIC and TRPV1 may play a coordinated and interactive role in processing the muscle afferent response to metabolites. In HF, cardiovascular responses to activation of metabolite-sensitive TRPV1 are blunted as compared with healthy control. These data suggest that abnormalities in those receptors in primary afferent nerve may initiate the development of an exaggerated sympathetic activity in HF. The long-term goal of our research is to extend investigations on the cellular and molecular mechanisms of neural control and cardiovascular regulation in heart failure.