Neural control of blood pressure (BP) involves both short-term, """"""""beat-to-beat"""""""" regulation as well as longer, more tonic control of mean pressure. Two functional types of carotid sinus baroreceptors, which have been described previously, have been found to contribute differentially to these two aspects of BP control. Type I baroreceptors have been found to contribute more to dynamic control of BP, while Type II baroreceptors have been found to be major regulators of tonic BP. However, the site of elaboration of this differential baroreceptor control of BP is not known. Some differential control of BP may be due to the different patterns of afferent input from the two subtypes of baroreceptors. In addition, preliminary data indicates that afferent input from the baroreceptor subtypes may be directed to at least two different populations of neurons in the nucleus tractus solitarius (NTS), thought to be the site of the first synapse for baroreceptor afferent input in the CNS. Firing patterns of neurons from these two populations of NTS baroreceptor-modulated neurons are different. The first type of central neuron has an abrupt onset of discharge during pressure ramp stimulation of the carotid baroreceptors, which rapidly adapts in spite of continued baroreceptor activation. The second has ongoing discharge that is increased during carotid baroreceptor activation and does not show adaptation. Thus, in addition to the contributions of baroreceptor firing patterns to differential control of BP, selective activation of NTS baroreceptor-modulated neurons with different firing characteristics may also help regulate differential patterns of outflow of the autonomic nervous system. Studies have provided evidence that glutamate (GLU) is the primary neurotransmitter released by baroreceptor afferent fibers at the second order neurons in the NTS. However, the type of GLU receptors found on the second order neurons has not been established. Evidence exists for a role for NMDA, non-NMDA, metabotropic or combined types of receptors at putative baro-sensitive neurons in the NTS, although no functional role has been assigned for the receptors. The potential for differential distribution of glutamate receptors which initiate responses with different time courses and effects on the NTS neurons may contribute to the differential control of BP. Therefore, the overall aim of the present study is to examine static and dynamic characteristics of baroreceptor-modulated neurons in the NTS which may contribute to differential control of BP, with the intent of determining the contribution of GLU receptor subtype to the discharge of the NTS neurons activated by specific baroreceptor subtypes. The information obtained from these studies may provide insights into mechanisms of differential control of blood pressure under normal conditions and how alteration of this control may lead to pathologic states, including hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL055490-02
Application #
2460174
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1996-08-01
Project End
2000-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Seagard, J L; Dean, C; Hopp, F A (2003) Activity-dependent role of NMDA receptors in transmission of cardiac mechanoreceptor input to the NTS. Am J Physiol Heart Circ Physiol 284:H884-91
Seagard, J L; Dean, C; Hopp, F A (2001) Properties of NTS neurons receiving input from barosensitive receptors. Ann N Y Acad Sci 940:142-56
Seagard, J L; Dean, C; Hopp, F A (2000) Modulation of the carotid baroreceptor reflex by substance P in the nucleus tractus solitarius. J Auton Nerv Syst 78:77-85
Seagard, J L; Dean, C; Hopp, F A (2000) Neurochemical transmission of baroreceptor input in the nucleus tractus solitarius. Brain Res Bull 51:111-8
Cowan, A R; Dean, C; Bago, M et al. (2000) Potentiation of non-N-methyl-D-aspartate receptor-induced changes in blood pressure by substance P in rats. Neurosci Lett 278:161-4
Seagard, J L; Dean, C; Hopp, F A (1999) Role of glutamate receptors in transmission of vagal cardiac input to neurones in the nucleus tractus solitarii in dogs. J Physiol 520 Pt 1:243-53
Hopp, F A; Seagard, J L (1998) Respiratory responses to selective blockade of carotid sinus baroreceptors in the dog. Am J Physiol 275:R10-8