The focus of this proposal is to examine the hypothesis that the activity of the GABAergic and glutamatergic neurotransmitter systems differs between male and female rats as well as during the estrus cycle in female animals resulting in an attenuated sympathoexcitation in females compared to males. To address this overall hypothesis, the specific aims of this proposal are: 1. To determine the role of GABA in the PVN in modulating sympathetic control of arterial pressure in male and female rats. The extent of tonic GABAergic inhibition through GABA-A and GABA-B receptors will be assessed by microinjection of antagonists into the PVN. 2. To determine differences between male and female rats in activating descending sympathetic nervous system pathways from the PVN by stimulation of glutamate receptors. Glutamate receptor subtype function will be assessed by microinjection into the PVN of specific agonists. Endogenous glutamatergic receptor function will be determined by administration of specific glutamate antagonists following blockade of tonic GABA inhibition or glutamate uptake in the PVN. 3. To ascertain the role of the baroreflex in buffering increases in arterial pressure and heart rate resulting from excitation of the PVN. Sinoaortic deafferentation will be used to determine if alterations in baroreflex function influence differences in sympathoactivation between male and female animals. 4. To initiate studies assessing signal transduction pathways involved in glutamate neurotransmission in the PVN of female animals. The role of phosphorylation of the glutamate receptor will be studied using pharmacological interventions to begin to delineate cellular responses to receptor stimulation.
NIH ExPorter
NIH ExPorter