NEUROTRANSMITTERS AND CENTRAL CONTROL OF BLOOD PRESSURE

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The nucleus tractus solitarius (NTS) has been extensively studied with respect to its physiologic functions and histochemistry; yet little is known of the relationship between those functions and the putative transmitters identified in the NTS. Knowledge of such relationships could aid in understanding how some of those physiologic functions are mediated and integrated with each other and could reveal potential mechanisms for the genesis of hypertension and for controlling blood pressure pharmacologically. The goal of this project, then, will be to determine relatioships between ten neurotransmitters and six physiologic functions (blood pressure, heart rate, respiratory rate, electrocortical activity, gastric motility, and sympathetic nerve activity) modulated by the NTS. Particular emphasis will be placed on the baroreceptor reflex and on establishing the integral role played by L-glutamate in mediating that reflex. It is anticipated that each putative transmitter microinjected into the NTS will elicit a distinct profile of physiologic responses and that respective antagonists will block those responses. Those angonists which produce, in their physiologic profile, changes in blood pressure and heart rate will be further studied to determine their relationship to the baroreceptor reflex. Those putative transmitters integral to the baroreceptor reflex will be identified by the ability of their antagonists to block the reflex and to produce neurogenic hypertension, an invariable acute result of interruption of the baroreceptor reflex centrally or peripherally. To provide physiologic evidence for release of the relevant transmitters from baroreceptor afferents (or other vagal afferents), supersensitivity to the injection of the agonists will be sought by studying their dose responses at intervals after the unilateral removal of the nodose ganglion. Since a major focus of the work will be the central control of blood pressure in the NTS, changes in the sensitivity to agonists active in cardiovascular regulation (as identified above) will be sought in one form of spontaneous hypertension, the spontaneously hypertensive rat.