The nucleus tractus solitarii (NTS) plays a critical role in cardio- vascular regulation. Glutamate (GLU) is a putative neurotransmitter in cardiovascular regions of the NTS where nitric oxide (NO) or nitrosyl factors elicit cardiovascular responses similar to those produced by GLU. Activation of GLU receptors at other central sites has been shown to cause release of NO, but studies have not been done to determine if GLU influences NO in NTS and, if so, if NO contributes to responses to GLU. Preliminary data suggest that GLU and NO containing nerves lie in close proximity in NTS and that inhibition of synthesis of NO by local neurons attenuates responses to GLU. The hypothesis of the current study is that responses to GLU in NTS are linked to NO. There are four specific aims.
The first aim i s to determine if NO participates in mediating cardiovascular effects produced by GLU receptor agonists in the NTS. Pharmacological studies will assess cardiovascular responses to injection of GLU agonists into the NTS of awake, unrestrained rats both before and after injection at the same site of reduced hemoglobin, a scavenger of NO; an inhibitor of neuronal NO synthase; L-arginine, the precursor of NO; or a donor of NO The second aim is to determine if NO is released from the NTS exposed to GLU receptor agonists. This in vitro neurochemical study will utilize freshly prepared tissue from NTS dissected from slices of rat brain stem and will measure NO by the chemiluminescence method.
The third aim i s to determine if effects of GLU on soluble guanylate cyclase are mediated through NO. An in vivo study will determine if blockade of soluble guanylate cyclase, an important step in signal transduction mediated by NO, alters responses to GLU microinjected into the NTS of awake rats. An in vitro study will directly assess effects of GLU on formation of cyclic GMP and will study the role of NO in producing those effects.
The fourth aim i s to determine the anatomical relationship between GLU terminals and neuronal elements that contain NO synthase (NOS) in the NTS. These studies will be important in expanding our understanding a) interrelationships between two putative transmitters in the NTS, b) the role of NO or nitrosyl factors in generating cardiovascular responses from NTS and c) cardiovascular influences of NTS in awake animals.
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