This is a revised application for continuation of support to study the electrophysiological properties of neurons in the medial nucleus of the tractus solitarius (mNTS) in rats. Baroreflex function is impaired in chronic hypertension.Several studies implicate a defect within the central nervous system as a causative (or at least a contributing factor) in some forms of hypertension. The central hypothesis to be tested is that the development of hypertension is accompanied by changes in the physiological and pharmacological properties of mNTS neurons contained within the baroreceptor reflex pathway.The proposed experiments will use a combination of electrophysiological and anatomical techniques in vivo and in vitro to characterize intrinsic membrane properties, synaptic mechanisms, and selected neurotransmitter- receptor interactions that influence the activity of mNTS neurons in four groups of normotensive and age-matched hypertensive rats: normotensive Wistar-Kyoto (NT-WK), normotensive Sprague-Dawley (NT-SD), Grollman hypertensive Sprague-Dawley (GH-SD) or DOCA-salt hypertensive Sprague- Dawley (DS-SD), and spontaneously hypertensive (SH) rats.The studies are designed to address five Specific Aims.
The first aim i s to compare the cellular properties of mNTS neurons in normotensive and hypertensive rats. Some of the factors to be studied by using intracellular recordings include membrane resistance and time constants, spike frequency adaptation, post- burst after hyperpolarization, delayed excitation, post-inhibitory rebound, and ionic currents.
The second aim i s to determine if the responses of mNTS neurons to synaptic activation [i.e., area postrema (AP) stimulation] or antidromic activation is changed in hypertensive rats.
The third aim i s to test the effects of hypertension on alpha-adrenergic receptor modulation of synaptic events in mNTS neurons. Specifically, the investigators will determine if adrenergic modulation of mNTS neurons by AP stimulation is modified in hypertension.
The fourth aim i s to characterize the central abnormality in baroreflex control in hypertension in vivo. For this purpose they will determine whether the defect depends upon such factors as input from circumventricular organs or changes in central respiratory drive.The fifth aim is to determine if different hypertensive models have similar central disturbances. The morphology and projections of many of the neurons they record from will be identified by intracellular labelling with biocytin.
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