Studies of a Bulbospinal Pathway that Regulates Cardiovascular Function: Inhibition by GABA at the Ventral Medulla and Mediation by Spinal Cord Substance P
Abstract
The central nervous system plays a prominent role in regulating the cardiovascular system, and the ventral medulla (VM) specifically has been the focus of recent attention as a brain region important in cardiovascular control. Pharmacologic approaches were used to characterize the role of the VM and the mechanisms by which information is relayed to the heart and vasculature. Initially, experiments were done to evaluate a rat model for studying the cardiovascular effects of pharmacologic manipulations of the VM. GABAergic drugs were used because of their well-characterized actions at the VM in other species. GABA and the GABA receptor agonist, muscimol, applied to a discrete region of the exposed surface of the VM, produced dose-dependent decreases in mean arterial pressure (MAP) and heart rate (HR) that were reversed with the GABA receptor antagonist, bicuculline. Bicuculline alone raised MAP and HR. The GABAergic drug-induced effects were blocked by sympathetic blockers injected intravenously. The most sensitive site was localized to an intermediate area on the surface of the VM. Topical application of [3H]GABA to this intermediate area resulted in labeling that was concentrated at the site of application, measured quantitatively and autoradiographically, and most closely corresponded to the lateral paragigantocellular nucleus. These data provided evidence for a neuronal system near the surface of the VM of the rat that increases sympathetic outflow to the cardiovascular system and is tonically inhibited by GABA. Because substance P (SP) is contained in VM projections to the intermediolateral cell column (IML) of the spinal cord, and SP excites sympathetic preganglionic neurons when injected into the IML, the second series of experiments were done to determine if SP in the spinal cord was responsible for mediating the GABAergic effects. Anesthetized ratswere given intrathecal (i.t.) injections of SP antagonists.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 13, 1984
- Accession Number
- AD1010713
Entities
People
- Jill R. Keeler
Organizations
- Uniformed Services University of the Health Sciences