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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL029302-10
Application #
2216427
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1984-03-01
Project End
1996-12-31
Budget Start
1995-01-01
Budget End
1995-12-31
Support Year
10
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Iowa
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Hayward, Linda F; Riley, Alecia P; Felder, Robert B (2002) alpha(2)-Adrenergic receptors in NTS facilitate baroreflex function in adult spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 282:H2336-45
Hayward, L F; Johnson, A K; Felder, R B (1999) Arterial chemoreflex in conscious normotensive and hypertensive adult rats. Am J Physiol 276:H1215-22
Sundaram, K; Johnson, S M; Felder, R B (1997) Altered expression of delayed excitation in medial NTS neurons of spontaneously hypertensive rats. Neurosci Lett 225:205-9
Hegarty, A A; Felder, R B (1997) Vasopressin and V1-receptor antagonists modulate the activity of NTS neurons receiving baroreceptor input. Am J Physiol 273:R143-52
Ma, S; Abboud, F M; Felder, R B (1995) Effects of L-arginine-derived nitric oxide synthesis on neuronal activity in nucleus tractus solitarius. Am J Physiol 268:R487-91
Hegarty, A A; Hayward, L F; Felder, R B (1995) Sympathetic responses to stimulation of area postrema in decerebrate and anesthetized rats. Am J Physiol 268:H1086-95
Hayward, L F; Felder, R B (1995) Cardiac rhythmicity among NTS neurons and its relationship to sympathetic outflow in rabbits. Am J Physiol 269:H923-33
Hayward, L; Hay, M; Felder, R B (1993) Acute resetting of the carotid sinus baroreflex by aortic depressor nerve stimulation. Am J Physiol 264:H1215-22
Hajduczok, G; Hade, J S; Mark, A L et al. (1991) Central command increases sympathetic nerve activity during spontaneous locomotion in cats. Circ Res 69:66-75
Felder, R B; Mifflin, S W (1988) Modulation of carotid sinus afferent input to nucleus tractus solitarius by parabrachial nucleus stimulation. Circ Res 63:35-49

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