Current Research Questions
We want to know the source of tonic Neuropeptide Y inhibition of paraventricular presympathetic neurons and how this inhibition changes. Our specific questions include:
· Does select excitation or inhibition of arcuate Neuropeptide Y neurons decrease or increase sympathetic nerve activity?
· What neurotransmitters alter the activity of arcuate Neuropeptide Y neurons involved in the regulation of sympathetic nerve activity?
We aim to understand why obesity increases sympathetic nerve activity, which contributes to hypertension development and end-organ damage. Our specific questions include:
· What are the brain sites and cellular-molecular mechanisms by which obesity increases the sympathoexcitatory effects of insulin and leptin?
· Are there sex differences in obesity-induced sympathoexcitation?
We want to identify the mechanisms by which normal and hypertensive pregnancy increases sympathetic nerve activity. Our specific questions include:
· What are the brain sites and cellular-molecular mechanisms by which pregnancy increases sympathetic nerve activity?
· How do these mechanisms change in hypertensive pregnant rats?
The sympathetic nervous system contributes to short-term control of blood pressure via the baroreceptor reflex (above), a negative feedback system that includes pressure sensors in major arteries, brain processing of the sensory information, and changes in the activity of the sympathetic nervous system. For example, when arterial blood pressure falls (put mouse over the aorta—the artery leaving the heart), this is detected by decreased stretch and firing of nerve endings in the aortic wall, which is relayed to the brain. The signal is relayed through multiple nerves in the hindbrain (lilac), and ultimately causes heart rate and activity of sympathetic nerves to increase. We have found that pregnancy attenuates the function of the baroreflex, such that responses of the sympathetic nervous system to low blood pressure are inadequate (put mouse on aorta). We are currently investigating whether changes in the levels of the gaseous neurotransmitter, nitric oxide, or in insulin sensitivity cause these deleterious changes in baroreflex function.
We are also trying to understand why increased dietary salt increases the activity of the sympathetic nervous system and blood pressure in people with hypertension. Our current idea is that salt activates the brain to increase sympathetic tone (put mouse on sympathetic nerve innervating blood vessel), much like salt activates the brain to stimulate thirst. We are probing specific brain regions important in controlling the firing rate of sympathetic nerves (put mouse on brain), and have found that salt rapidly and profoundly increases the sensitivity of these regions to neurotransmitters such as glutamate, the most important excitatory brain transmitter. Ongoing experiments are investigating, on molecular, cellular, and integrative levels, the mechanisms for these changes in brain function.