NEUROCHEMICAL STUDIES OF CNS CARDIOVASCULAR CENTERS

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There are several drugs currently used to treat hypertension which appear to act on the cardiovascular control centers of the central nervous system. Such drugs include clonidine and Alpha-methyldopa, both of which are Alpha2-adrenergic receptor agonists. Other CNS receptors may also be involved in hypertensive states and their identity might lead to the development of new anti-hypertensive drugs. We wish to study the distribution of five neurotransmitter and their corresponding receptors in central nervous system cardiovascular control centers (for example, the nucleus ambiguus, nucleus of the Xth nerve, nucleus of the solitary tract and the intermediolateral column of the spinal cord), in order to determine which drugs may potentially act at these sites. Markers for adrenergic, cholinergic, gamma-aminobutyric acid, glutamate, and serotonin transmission and their receptors will be detected by light microscope histochemistry and autoradiography. Receptor concentrations of cardiac and vasomotor control centers in adult rats will also be determined after deafferentation and axotomy. The changes observed will indicate whether the receptors tested are localized pre- or postsynaptically. In addition, the concentration of neurotransmitter and drug receptors in the cardiovascular control centers of neonatal and adult normotensive and spontaneously hypertensive rats will be compared. This comparison might reveal the chemical nature of central transmitter system malfunction underlying hypertension.