Abstract 410: Hyptertension and Baroreflex Dysfunction After Loss of Glia in Rat NTS
Injection into the rat NTS of anti-dopamine-beta-hydroxylase-saporin (anti-DBH-SAP), which causes local loss of neuronal DBH immunoreactivity (IR), or of stabilized substance P- SAP (SSP-SAP), which causes local loss of neuronal neurokinin-1 receptor (NK1R) IR, leads to lability of arterial pressure and diminished arterial baroreflex function. We have found that anti-DBH-SAP and SSP-SAP also lead to loss of IR for glial fibrillary acidic protein (GFAP) in the NTS. To further characterize cellular changes produced by introducing into the NTS conjugates containing SAP, we sought to compare and contrast cardiovascular effects of anti-DBH-SAP, SSP-SAP, SAP (unconjugated), blank-SAP (non-targeted peptide conjugate), 6-hydoxydopamine (6-OHDA, a neurotoxin without SAP) and PBS injected into NTS. We assessed effects of injected agents both on cellular markers [NMDAR1 (NMDA receptor subunit 1), GluR2 (AMPA receptor subunit 2), neuronal nitric oxide synthase (nNOS), tyrosine hydroxylase (TH), vesicular glutamate transporters (VGluTs), choline acetyl transferase (ChAT), GFAP, connexin 43 (Cx43), DBH, NK1R and protein gene product 9.5 (PGP 9.5)] and on arterial pressure and baroreflex function. We found that each compound containing SAP (including blank-SAP and unconjugated SAP) led to loss of GFAP and Cx43 immunofluorescent labeling in the NTS as well as lability of arterial pressure. Those outcomes occurred despite neuronal specificity for each of the SAP conjugates. For example, anti-DBH-SAP decreased TH/ DBH IR but not NK1R IR in NTS while SSP-SAP led to loss of NK1R IR as well as glutamate receptors but not DBH IR. SSP-SAP also caused PGP9.5 loss, not seen with other agents. SAP and blank-SAP, on the other hand, led to loss of GFAP and Cx43 but no loss of neuronal markers. Injection of SAP alone in NTS led to significantly attenuated baroreflex responses and to significant hypertension. In contrast, 6-OHDA led to loss of TH and DBH IR and decreased Cx-43, but it increased GFAP. No baroreflex or cardiovascular effects were seen after injection of 6-OHDA, which spared glia. This study supports a critical role for NTS glia in central cardiovascular control and in maintenance of normal blood pressure.
- © 2012 by American Heart Association, Inc.