- Brain Awareness Week
Neural mechanisms of cardiovascular regulation. Baroreflex function in health and disease
Dr. Chapleau's research program focuses on neural mechanisms that regulate arterial blood pressure and cardiovascular function. The baroreceptor reflex is a key mechanism of blood pressure regulation. Major goals of the research program are to define the molecular mechanisms influencing mechanoelectrical transduction and neuronal excitability in baroreceptor neurons, and to delineate mechanisms responsible for excessive sympathetic nerve activity and decreased baroreflex sensitivity in pathological states (e.g., hypertension, hypercholesterolemia, atherosclerosis) and in aging.
Ongoing projects in the laboratory address the following topics:
(1) The role of specific K+ and Na+ channels in modulation of excitability of baroreceptor afferent neurons. (2) The role of reactive oxygen species in mediating autocrine activity-dependent inhibition of baroreceptor activity under physiological conditions. (3) The contribution of chronic oxidative stress to impairment of baroreflex/autonomic function in hypertension, atherosclerosis, and aging. (4) The interactions that enhance baroreflex/autonomic dysfunction in subjects with both hypertension and atherosclerosis at young and old ages. (5) The ability of angiotensin and other humoral/autocrine factors to modulate sympathetic nerve activity through direct actions on neurons in sympathetic ganglia, and the cellular mechanisms of their actions. Experimental approaches include: 1) recording of baroreceptor activity and reflex changes in sympathetic nerve activity in genetically-modified mice in vivo; 2) long-term recording of blood pressure and heart rate in conscious unrestrained mice using radiotelemetry; 3) recording K+ and Na+ currents from isolated baroreceptor and sympathetic neurons in culture (sharp electrode and patch-clamp techniques); 4) fluorscent imaging of reactive oxygen species and calcium in baroreceptor and sympathetic neurons; and 5) manipulation of gene expression in baroreceptor and sympathetic neurons using adenoviral-mediated gene transfer.