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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL034472-04
Application #
3347396
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1988-09-01
Project End
1991-03-31
Budget Start
1988-09-01
Budget End
1991-03-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Frostholm, A; Zdilar, D; Chang, A et al. (1991) Stability of GABAA/benzodiazepine receptor alpha 1 subunit mRNA expression in reeler mouse cerebellar Purkinje cells during postnatal development. Brain Res Dev Brain Res 64:121-8
Zdilar, D; Rotter, A; Frostholm, A (1991) Expression of GABAA/benzodiazepine receptor alpha 1-subunit mRNA and [3H]flunitrazepam binding sites during postnatal development of the mouse cerebellum. Brain Res Dev Brain Res 61:63-71
Russo-Neustadt, A; Rotter, A; Frostholm, A (1991) Distribution of muscarinic receptors in the developing rodent cerebellum. Brain Res 548:179-86
Rotter, A; Gorenstein, C; Frostholm, A (1988) The localization of GABAA receptors in mice with mutations affecting the structure and connectivity of the cerebellum. Brain Res 439:236-48
Neustadt, A; Frostholm, A; Rotter, A (1988) Topographical distribution of muscarinic cholinergic receptors in the cerebellar cortex of the mouse, rat, guinea pig, and rabbit: a species comparison. J Comp Neurol 272:317-30
Rotter, A; Frostholm, A (1988) Cerebellar benzodiazepine receptors: cellular localization and consequences of neurological mutations in mice. Brain Res 444:133-46
Frostholm, A; Rotter, A (1987) The ontogeny of [3H]muscimol binding sites in the C57BL/6J mouse cerebellum. Brain Res 465:157-66
Rotter, A; Frostholm, A (1986) Cerebellar benzodiazepine receptor distribution: an autoradiographic study of the normal C57BL/6J and Purkinje cell degeneration mutant mouse. Neurosci Lett 71:66-71